Copyright by Penelope F. Frohlich 2003 - The University of ...

Copyright

by

Penelope F. Frohlich

2003

The Dissertation Committee for Penelope F. Frohlich

certifies that this is the approved version of the following dissertation:

The Role of Tactile Sensitivity in

Female Sexual Dysfunction

Committee: ________________________________ Cindy Meston, Supervisor ________________________________ David Buss ________________________________ Elizabeth Edmundson ________________________________ Dennis McFadden ________________________________ Timothy Schallert ________________________________ Michael Telch



by

Penelope F. Frohlich, B.A., M.A.

Dissertation

Presented to the Faculty of the Graduate School of

the University of Texas at Austin

in Partial Fulfillment

of the Requirements

for the Degree of

Doctor of Philosophy

The University of Texas at Austin

May 2003

Dedication

To my husband, David

Acknowledgements

I would like to thank my supervisor, Cindy Meston, for her many

efforts to nurture my professional as well as personal growth. Among

many other things, she spent numerous hours proofreading and editing

my various manuscripts, discussing research hypotheses and

methodology, and preparing grants and fellowships. She took every

opportunity to nominate me for grants and fellowships, to offer publication

opportunities, and to offer additional funding when available. In addition,

she is one of the most interesting, unique, humorous, and talented

individuals I have met, and I have many fond memories of the fun we have

had together. I hope that we will continue our friendship in the years to

come.

I would also like to thank the members of my dissertation

committee: David Buss, Elizabeth Edmundson, Dennis McFadden,

Timothy Schallert, and Michael Telch. They offered suggestions and

ideas that greatly improved the quality of my dissertation. In addition, they

never hesitated to challenge my intellect and fortitude – now that my

dissertation is complete, I am able to appreciate their efforts, and

remember my proposal and defense with fondness.

v

I would also like to thank the many, many research assistants who

help collect my dissertation data. Over the three years that I collected my

dissertation data, approximately 30 students and volunteers helped in this

effort. Many of these students were remarkable individuals who have

gone on to successful careers of their own. I have continued to remain in

contact with several, such as Annie Bradford, Monica Calderon, and

Simran Sahni, and it is a pleasure to continue and build a friendship with

each of these ladies. I would like to especially note two research

assistants who contributed the greatest help to my dissertation. Annie

Cohen, who helped with the earliest stages of my dissertation proposal,

and photocopied hundreds of journal articles with surprising accuracy and

speed. She was intelligent and resourceful and it was no surprise when

she went on to her own graduate training in neuroscience. Tonya

McDaniels, who is one of the most talented, intelligent, and ethical

students I have known; I have little doubt that she will be among the most

successful of my students – she too has gone on to her own graduate

training in human sexuality.

I would also like to thank Eli Lilly for donating the study medication,

Prozac. Without this assistance, the second study of my dissertation

would not have been possible.

vi

I would also like to thank my family. My brothers and sisters, Tom,

Molly, Chovy, Xaq, Honus, & Violet, who have always been a source of

support, delight, and humor, and who I cannot and do not wish to imagine

my life without. Jackie, who has shown me that it is possible to enjoy both

academic pursuits and traditionally feminine pursuits, and for helping to

bring happiness to my father’s life – I am often and will always be grateful

for this. Ruth, who is one of the more generous people I have known, and

who has always been available for me in a crisis. My father, who taught

me independence and fortitude, invaluable assets in graduate school, and

who was always available to offer advice and support through the often

difficult and confusing process of graduate training.

I would also like to thank my friends, in no particular order, Susana

Kugeares, Lisa Redford, Shannon Kasperkievicz, Harrell Woodson, and

Michael Bergman. Susana is articulate and hilarious, and was always the

best person to turn to when my emotions where overwhelming. Lisa is

knowledgeable on a broad range of topics, and is interesting and

thoughtful, and I wish terribly that she didn’t live so far away. Shannon is

my oldest friend, and we will surely grow old together – she is generous,

kind, intelligent, and always adventurous. Harrell is my newest friend, he

helped me survive internship and the final brutal months of my dissertation

vii

– I’m so pleased that we have continued our friendship and look forward to

helping each other survive the transition into our professional lives.

Finally, Michael, who is better known as Young Mike, and who is “sweet

as pie” and who has always “been right there for me.”

Finally, I would like to acknowledge and thank my husband David.

The few short years we have spent together have easily been the happiest

of my life and I feel blessed to have met him. Knowing him has changed

me – despite all my academic education, I have been, ironically, quite

ignorant. David has opened a new world to me that is fuller and richer. I

pray that I will not lose him and that I will never have to return to the life I

had before him. David, you touch me, that is everything, and I love you.

viii



Publication No. __________

Penelope F. Frohlich, Ph.D. The University of Texas at Austin, 2003

Supervisor: Cindy Meston

Convergent evidence suggests tactile sensitivity may be associated

with sexual dysfunction in women. Both tactile sensation and female

sexual functioning are affected by variations in estrogen levels,

sympathetic nervous system activation, and vascular functioning. In

addition, antidepressant-induced sexual dysfunction (with selective

serotonin reuptake inhibitors such as fluoxetine) may be mediated by

changes in tactile sensation. Serotonin is active in several peripheral

mechanisms likely to affect sexual functioning such as vasoconstriction

ix

and dilation, smooth muscle contraction, and innervation of the genitals.

Two studies were conducted to examine these hypotheses.

In Study 1, tactile sensitivity was examined on the index finger and

lower lip in women with Female Sexual Arousal Disorder (FSAD; n = 15),

Female Orgasm Disorder (FOD; n = 17), and normally functioning women

(n = 17). Finger and lip threshold were significantly associated with FSAD

versus control women, and finger threshold with severity of FSAD. Finger

and lip threshold were not significantly associated with FOD versus control

women, or severity of FOD. In Study 2, tactile sensitivity was examined at

baseline (pre-medication), week 1, week 4, and week 8, in clinically

depressed women, 12 of whom received fluoxetine treatment and 13 of

whom did not. Fluoxetine treatment resulted in decreased orgasm

functioning, but not sexual desire or arousal functioning. Analyses

indicated that fluoxetine-induced sexual changes were not mediated by

tactile sensation. Consistent with previous findings, an independent

association was found between sexual arousal functioning and finger

sensation. Novel to this study, an independent association was found

between sexual desire and finger sensation.

Findings from the two studies suggest that tactile sensation may

serve as a physiological assessment tool for FSAD. Future studies will

x

need to examine whether tactile sensation measurements differentiate

between subtypes of FSAD, and other types of sexual disorders, such as

Hypoactive Sexual Desire Disorder. Future studies will also need to

examine the association between sexual functioning and other aspects of

tactile sensation, such as vibrotactile, temperature, and pain sensation,

and nerve conduction velocity, on both genital and non-genital regions of

the body.

xi

Table of Contents

List of Tables..................................................………….......………......... xvii

List of Figures....................................................…………….......……..... xviii

List of Appendices…………………………………………………....……… xx

Chapter 1: Introduction 1.1 The Role of Tactile Sensitivity in Female Sexual Dysfunction……… 1

1.2 Tactile Receptors………………………………………...……………… 3

1.2.2 Tactile Sensation in the Genitals………………………….… 8

1.3 Female Sexual Anatomy and Physiology…………………………..… 9

1.4 Tactile Sensitivity and the Sexual Response Cycle……………….… 13

1.5 Tactile Sensitivity and Sexual Dysfunction: Role of Serotonin…..…. 19

1.5.1 Serotonin in the Female Genital Tract…………….………... 20

1.5.2 Serotonin and Non-vascular Smooth Muscle

Contraction……………………………………………………. 21

1.5.3 Serotonin and Endocrine Functions…………………….…... 23

1.5.4 Serotonin and Vascular Mechanisms……………………..… 26

1.5.5 Serotonin in the Spinal Cord and Peripheral Nerves…..….. 33

1.5.6 Acute versus Chronic Effects of Serotonin……………….... 35

1.6 Selective Serotonin Reuptake Inhibitors, Sexual Dysfunction, and

Tactile Sensitivity…………………………………………….………. 36

Chapter 2: Present Study 2.1 Study 1: The Role of Tactile Sensitivity in Female Sexual Arousal

Disorder and Female Orgasm Disorder………………………………..….. 42

2.1.2 Severity of Sexual Dysfunction and Tactile Sensation.…… 45

2.2 Study 2: The Effect of Fluoxetine on Tactile Sensitivity and Sexual

Functioning…………………………………………….………….….. 46

xii

2.2.1 Analysis of Fluoxetine-Use and Tactile Sensitivity……..….. 46

2.2.2 Analysis of Fluoxetine-Induced Sexual Dysfunction…….… 49

2.2.3 Tactile Sensation as a Mediator of Fluoxetine-Induced

Sexual Dysfunction………………………..………….……… 49

Chapter 3: Methods 3.1 Study 1: The Role of Tactile Sensitivity in Female Sexual Arousal

Disorder and Female Orgasmic Disorder………………..………... 51

3.1.1 Overview of Experimental Design…………………………… 51

3.1.2 Participants…………………………….………….…………… 51

3.1.2a Participant Selection: Questionnaires…………..…. 52

3.1.2b Participant Selection: Clinical Interview………....… 55

3.1.3 Covariates…………………………………………….……...... 59

3.1.4 Measures…………………………….………………….……... 61

3.1.4a Self-Report Measures………………………….….... 61

3.1.4b Physiological Measures………………………..….... 65

3.1.5 Procedure……………………………………………..……….. 66


Functioning………………………………………………….….…..… 69

3.2.1 Design……………………………………………….….…….... 69

3.2.2 Participants………………………………………….….……… 70

3.2.3 Medication………………………………………….………….. 72

3.2.4 Materials……………………………………………….……..... 72

3.2.5 Procedure…………………………………….……….……….. 73

Chapter 4: Statistical Analyses 4.1 Tactile Sensitivity Threshold…………………………….………….….. 74

4.2 Study 1: The Role of Tactile Sensitivity in Female Sexual Arousal

Disorder and Female Orgasmic Disorder…………………………..……... 74

xiii

4.2.1 Analytic Strategy………………………………………..……... 74

4.2.2 Specific Analyses…………………………………….……….. 75

4.2.2a Analysis of Group Differences in Sexual

Functioning……………….……………….………….. 75

4.2.2b Covariates…………………………….…….………... 76

4.2.2c Analysis of Female Sexual Arousal Disorder,

Female Orgasm Disorder, and Tactile

Sensitivity……………………………………………... 77

4.2.2d Analysis of Severity of Sexual Dysfunction and

Tactile Sensitivity……………………………..…….... 78


Functioning…………………………………….…….……………….. 79

4.3.1 Data Selection………………………………………………..... 79

4.3.2 Analytic Strategy……………………………………………..... 80

4.3.2b Hierarchical Linear Modeling………………..…….... 81

4.3.3 Specific Analyses……………………………………………… 82

4.3.3a Fluoxetine-Induced Changes in Tactile

Sensitivity……………………………………………... 82

4.3.3b Manipulation Check: Analysis of Fluoxetine-

Induced Sexual Dysfunction……….……………….. 83

4.3.3c Analysis of Tactile Sensation as a Mediator of

Fluoxetine-Induced Sexual Dysfunction…………... 83

4.3.3d Mediation Effect……………………………..……….. 84

xiv

Chapter 5: Results 5.1 Study 1: The Role of Tactile Sensitivity in Female Sexual Arousal

Disorder and Female Orgasmic Disorder………………………..... 86

5.1.1 Analysis of Group Differences in Sexual Functioning…….. 86

5.1.2 Analysis of Tactile Sensation…………………………..…….. 87

5.1.3 Analysis of Covariates………………………………..……..... 90

5.1.4 Analysis of Tactile Sensitivity and Sexual Functioning….... 93

5.1.5 Severity of Sexual Dysfunction and Tactile Sensation

Threshold………….……………………………….…………. 98

5.1.6 Effect Sizes…………………………………………………..… 103


Functioning………………………………….……….……………….. 103

5.2.1 Analysis of Group Differences at Baseline………………..... 103

5.2.2 Analysis of Changes over Time……………………………... 103

5.2.3 Analysis of Fluoxetine-Induced Changes in Tactile

Sensation……………………….…………….………………. 105

5.2.4 Tactile Sensation as a Mediator of Antidepressant-Induced

Sexual Dysfunction………………………..…….… 109

5.2.4a Sexual Desire…………………………………..…….. 109

5.2.4b Sexual Arousal…………………………………..…… 114

5.2.4c Orgasm………………………………….……….….... 118

Chapter 6: Discussion 6.1 Study 1: The Role of Tactile Sensitivity in Female Sexual Arousal

Disorder and Female Orgasmic Disorder……………………..…... 122

6.1.1 Summary of the Main Findings………….………………...… 122

6.1.2 Female Sexual Arousal Disorder, Normally Functioning

Women, and Tactile Sensitivity…….................................. 122

xv

6.1.3 Female Orgasm Disorder, Normally Functioning Women,

and Tactile Sensitivity……………………………………...... 130


Functioning………………………………………………..………..… 134

6.2.1 Summary of the Main Findings…………………………….… 134

6.2.2 The Effect of Fluoxetine on Tactile Sensation…………..…. 135

6.2.3 Experimental Manipulation: Fluoxetine-Induced Sexual

Dysfunction………………………….………………….…….. 135

6.2.4 Tactile Sensation as a Mediator of Fluoxetine-Induced

Sexual Dysfunction…………………………….…………….. 137

6.2.5 Independent Association between Tactile Sensation and

Sexual Dysfunction……………………………………..….… 139

6.3 Limitations………………………………………….……….……………. 143

6.4 Directions for Future Research and Clinical Implications…………... 145

6.4.1 Tactile Sensitivity and Sexual Dysfunction…………..……... 145

6.4.2 Fluoxetine, Tactile Sensitivity, and Sexual Dysfunction…... 153

6.5 Conclusions……………………………………………..……………...... 156

Appendices…………………………………………………………..……….. 158

References………………………………………………………….………... 185

Vita……………………………………………………………..…………….... 219

xvi

List of Tables

Table 1: Group Differences in Sexual Functioning……………………..... 88

Table 2: Summary of Covariates……………………………….………...... 92

Table 3: Sexual Functioning in Fluoxetine and Control Groups at

Baseline…………………………………..…………………………. 104

xvii

List of Figures

Figure 1: Tactile Sensitivity on the Index Finger……………..…………… 89

Figure 2: Tactile Sensitivity on the Lips………………………….………... 89

Figure 3: FSAD vs. Control, Lip Threshold………………………..………. 95

Figure 4: FSAD vs. Control, Finger Threshold………………………….… 96

Figure 5: FOD vs. Control, Lip Threshold……………………………….… 97

Figure 6: FOD vs. Control, Finger Threshold…………………..…………. 97

Figure 7: Severity of Arousal Dysfunction and Lip Threshold…………... 100

Figure 8: Severity of Arousal Dysfunction and Finger Threshold…….… 100

Figure 9: Severity of Orgasm Dysfunction and Lip Threshold……….…. 102

Figure 10: Severity of Orgasm Dysfunction and Finger Threshold….…. 102

Figure 11: Finger Threshold……………………………………….……..… 106

Figure 12: Tactile Sensitivity on the Index Finger for the Fluoxetine

Group………………………………………………………..…….. 106

Figure 13: Lip Threshold………………………………………………..…… 108

Figure 14: Tactile Sensitivity on the Lips for the Fluoxetine Group…..… 108

Figure 15: Changes in Sexual Desire…………………………………...… 109

Figure 16: Independent Association: FSFI Sexual Desire and Finger

Threshold…………………………….…………………………… 111

Figure 17: Changes in Sexual Desire, Finger Threshold in Model……... 113

Figure 18: Changes in Sexual Desire, Lip Threshold in Model…….…... 113

Figure 19: Changes in Lubrication………………………………..………... 114

Figure 20: Independent Association between FSFI Lubrication Domain

and Finger Threshold………………………………..………...… 115

Figure 21: Changes in Lubrication, Finger Threshold in Model……....… 117

Figure 22: Changes in Lubrication, Lip Threshold in Model………….…. 117

Figure 23: Changes in Orgasm……………………………….………….… 118

xviii

Figure 24: Changes in Orgasm: Finger Threshold in Model…………..… 121

Figure 25: Changes in Orgasm: Lip Threshold in Model…………….….. 121

xix

List of Appendices

Appendix A: Beck Depression Inventory (BDI)………………………..….. 158

Appendix B: Beck Anxiety Inventory (BAI)……………….……………….. 162

Appendix C: Derogatis Sexual Functioning Inventory (DSFI)………..…. 163

Appendix D: Female Sexual Functioning Index (FSFI)………………..… 166

Appendix E: Female Sexual Satisfaction Scale (FSSS)………………… 172

Appendix F: Medical Information Questionnaire………….………….…... 174

Appendix G: Orgasmic Functioning Questionnaire (OFQ)…………….... 176

Appendix H: Sexual Functioning Index (SFI)…………………………....... 177

Appendix I: Modified - Medical Information Questionnaire………........... 180

Appendix J: Modified - Orgasmic Functioning Questionnaire…………… 181

Appendix K: Modified - Sexual Functioning Inventory………………....… 182

xx

CHAPTER 1: INTRODUCTION

1.1 The Role of Tactile Sensitivity in Female Sexual Dysfunction

The assessment and treatment of sexual dysfunction involves a

complex interaction between cognitive, physiological, and behavioral

components of the sexual response cycle. For example, women with

sexual arousal difficulties may experience, physiologically, a decrease in

vaginal vasocongestion and lubrication, cognitively, a mental feeling of

"not aroused" or "turned on," and, behaviorally, a decreased willingness or

desire to engage in vaginal penetration. Despite the importance of

combined assessment of these multiple response symptoms (e.g.,

Hawton, Salkovskis, Kirk, & Clark, 1991) clinical assessment protocols for

sexual dysfunction in women generally do not include measures of

physiological responsiveness. This is largely due to the fact that current

physiological measurement techniques (e.g., vaginal

photoplethysmography) have not been historically successful at

differentiating women with and without sexual dysfunction. For example,

some investigators have found that when exposed to an erotic stimulus

sexually functional and dysfunctional women differed in vaginal blood

volume (VBV) (Meston & Gorzalka, 1996a; Palace & Gorzalka, 1990,

1

1992; Wincze, Hoon, & Hoon, 1976) while other investigators have found

no difference (Morokoff & Heiman, 1980; Wincze, Hoon, & Hoon, 1978).

Together with the fact that vaginal photoplethysmography is a time

consuming, invasive procedure that requires highly specialized equipment,

the inconsistencies noted here suggest that vaginal

photoplethysmography may be of limited usefulness in assessing female

sexual dysfunction.

A non-invasive and inexpensive alternative to the vaginal

photoplethysmograph as an assessment tool for female sexual

dysfunction is the measurement of tactile sensitivity. Convergent evidence

suggests that tactile sensitivity may be important for sexual functioning

and suggests that alterations in tactile sensitivity may result in sexual

difficulties. The purpose of the present paper is to examine whether tactile

sensitivity may play an important role in female sexual dysfunction.

Mechanisms of tactile sensation and female sexual anatomy and sexual

physiology will be described followed by a discussion of the possible

relationship between tactile sensation and mechanisms underlying female

sexual functioning. Finally, two studies will be proposed that are designed

to determine whether variation in tactile sensitivity is associated with

variation in female sexual functioning.

2

1.2 Tactile Receptors

The skin contains receptors, known as cutaneous tactile receptors,

which detect mechanical and thermal stimulation. Most tactile receptors

detect a specific type of mechanical or thermal stimulation but some

receptors are able to detect both mechanical and thermal stimuli.

Nociceptors, or pain receptors, often respond to tissue-damaging levels of

mechanical or thermal stimuli (Munger, 1971 as cited in Munger & Ide,

1988) although some nociceptors discharge more readily to, for example,

tissue-damaging levels of mechanical but not heat stimuli (Davis, Meyer, &

Campbell, 1993; Schmidt, Schmelz, Ringkamp, Handwerker, & Toregjork,

1997). Similarly, thermoreceptors respond to either heat stimuli or cold

stimuli but rarely respond to both. Mechanoreceptors, which will be the

focus of this paper, respond to skin deformation or hair displacement

(Lynn & Carpenter, 1982). Mechanoreceptors are characterized by

several features: (1) the afferent unit -- the nerve pathway that transmits

sensory information from the peripheral sensory end organ to the spinal

cord (and thereby to the central nervous system); (2) the type of end

organ; (3) the receptive field -- the area of skin over which the

3

mechanoreceptor can detect skin deformation; (4) the degree of

sensitivity; and (5) the type of sensation evoked by stimulation.

Mechanoreceptor afferent units are either rapidly adapting or slowly

adapting. Slowly adapting mechanoreceptors (SA) are so named because

they respond to continuous stimulation. SA receptors are subdivided in

type I (SAI) and type II (SAII) (Ray & Kruger, 1983) depending upon

response to stimulation (Pubols & Pubols, 1983). Specific differences

between SAI and SAII receptors will be discussed in more detail below.

Rapidly adapting (RA) receptor types respond to changes in stimulation

while Pacinian corpuscles (Pc) are a special type of RA receptor that

provides only crude tactile sensation (Ray & Kruger, 1983).

Mechanoreceptors are often classified according to the type of end

organ. Free nerve endings, or unmyelinated receptors, differ from most

receptors because they are located in the dermis and epidermis, in the

hairy and hairless (glabrous) skin, and because they respond to painful or

nonpainful mechanical or thermal stimulation. Some free nerve endings

are multimodal; they respond to several forms of stimulation. In general,

though, free nerve endings primarily respond to pain or thermal stimuli and

only a few respond to only non-painful level of mechanical stimulation

(Shea & Perl, 1985). Free nerve endings are the most ubiquitous of all the

4

receptors. Groups of receptor cells typically synapse onto one afferent

unit, but unlike most tactile sensory receptors, free nerve endings are

characterized by a 1:1 relationship between the receptor cell and the

afferent unit. Afferent units of free nerve endings are classified as A delta

and C fibers (Munger & Ide, 1988). Other mechanoreceptor end organs,

however, are associated with either SA or RA afferent units.

Skin end organs for SAI and SAII receptors are Merkel tactile discs

and Ruffini corpuscles, respectively (Torebjork, Vallbo, & Ochoa, 1987).

The skin end organ for RA receptors is the Meissner corpuscle. The Pc

receptor is named according to its end organ, the Pacinian corpuscle

(Torebjork et al., 1987). In contrast, hair receptors often are innervated by

both SA and RA afferent units and as a result, some hair receptors

respond to multiple types of mechanical stimulation. Hair receptors are

unique in that the receptor unit is the hair follicle itself (Munger & Ide,

1988). Mechanoreceptors are frequently interchangeably referred to by

the name of the afferent unit or by the name of the end organ. For

example, a mechanoreceptor may be referred to as a Merkel tactile disc or

as a SAI mechanoreceptor.

Mechanoreceptors respond when the skin is displaced within a

discrete area of skin known as the receptive field. The receptive fields of

5

SAII and Pc receptors are large while SAI and RA receptive fields are

small. Specifically, SAII receptor fields are five times the size, and Pc

receptor fields are ten times the size, of SAI and RA receptors (Iggo &

Ogawa, 1977; Johansson & Vallbo, 1980). On the human hand, RA and

SAI receptors are most numerous on the finger tips while SAII and Pc

receptors are evenly distributed all over the hand (Johansson & Vallbo,

1979b).

Receptor types differ in their sensitivity to touch. On the human

hand, Pc and RA receptors require much lower levels of stimulation (9.2

and 13.8µm of displacement, respectively) than SAI and SAII receptors

(56.5 and 331µm of displacement, respectively) before stimulation is

perceived (Johansson, Vallbo, & Westling, 1980). Indeed, with the most

sensitive RA and Pc receptors, one nerve impulse can be sufficient for

conscious perception of stimulation while with SA receptors, a nerve could

discharge several times and still not lead to consciously perception

(Johansson & Vallbo, 1979a; Knibestol & Vallbo, 1980). Moreover,

stimulation intensity is related to perceived intensity for RA and Pc

receptors, but not for SA receptors (Johansson & Vallbo, 1979a; Knibestol

& Vallbo, 1980). That is, physical measurements of stimulation intensity

were similar to participant reports of stimulation intensity for RA and Pc

6

receptors but not for SA receptors. In addition, afferent unit thresholds are

similar in different skin regions while psychophysical thresholds are not.

This suggests that the central nervous system processes sensory input

from some areas of the body more accurately than it does from other

areas of the body (Johansson & Vallbo, 1979a; Johansson et al., 1980).

In addition to differences in touch sensitivity, each type of receptor

responds most readily to a particular kind of mechanical stimulation. SAI

receptors respond more to degree of skin displacement than to force of

displacement (Pubols, 1990) and SAI receptors do not respond to lateral

stretch while SAII receptors are sensitive to direction and stretch. Both

types of SA receptors respond to static as well as dynamic stimulation

(Knibestol, 1975). RA and Pc receptors respond when the stimulus is

applied and when it is removed -- this response pattern is known as

discharge at "on" and at "off". In addition, RA and Pc receptors are

sensitive to differing indentation velocities; the faster the velocity of

indentation, the faster the nerve discharges (Knibestol, 1973).

Stimulation of each receptor type results in a sensation of either

pressure, tapping, vibration, or tickling. Intraneural microstimulation of SAI

fibers with between 3 and 10 Hertz (Hz) results in a sensation of pressure.

Similar stimulation of RA receptors results in a sensation of tapping at low

7

frequencies (1-10 Hz), a sensation of vibration at higher frequencies (<100

Hz) but never results in a sensation of pressure or tickling. Stimulation to

Pc receptors, when between 10 and 80 Hz, results in a sensation of

vibration or tickling. Interestingly, SAII receptors respond to intraneural

stimulation, but even at frequencies as high as 100 Hz the stimulus is not

consciously perceived (Ochoa & Torebjork, 1983).

1.2.2 Tactile Sensation in the Genitals

The female genital tract is innervated by the pelvic, hypogastric,

and pudendal nerves. In the rat, the pelvic nerve innervates the vagina,

cervix, and perineum skin; the hypogastric nerve innervates the cervix and

the proximal three-fifths of the uterus, and the pudendal nerve innervates

the skin of the perineum, the inner thigh, and the clitoral sheath (Peters,

Kristal, & Komisaruk, 1987). The inner two-thirds of the vagina is

innervated only by pain receptors but the outer third, in particular, between

the vaginal wall and the bladder, is innervated by touch receptors known

as Merkel tactile discs (Krantz, 1958), which respond to steady pressure

(Valbo & Hagbarth, 1968). The external genitalia is more richly

innervated. The mons veneris, labia majora, labia minora, and the clitoris

are innervated by Meissner corpuscles, Merkel tactile discs, Pacinian

8

corpuscles, ruffian corpuscles, and pain receptors (Krantz, 1958; Yamada,

1951). Thus, the external genitalia are able to detect a wide range of

tactile stimulation.

Mechanical stimulation to the genital region suggests that different

areas of the genitalia respond to different types of stimulation. In the cat,

the external genitals contain high and low threshold SA receptors and low

threshold RA receptors. The vagina contains primarily RA receptors

although some SA receptors respond to deep pressure. The cervix

contains SA receptors that respond to pressure and velocity (Cueva-

Rolon, Munoz-Martinez, Delgado-Lezama, & Raya, 1994).

1.3 Female Sexual Anatomy and Physiology

Externally, the female genital tract consists of the mons veneris

(rounded portion or tissue above the clitoris that is covered, after puberty,

with pubic hair), clitoris, labia majora, labia minora, vestibule (the region of

tissue between the clitoris and the vaginal orifice), orifice of the urethra,

and the orifice of the vagina. Internally, the female genital tract consists of

the vagina, uterus, uterine horn, fallopian tubes, and ovaries. On either

side of the vagina, beneath the skin, lie Bartholin’s gland (Gray, 1966)

which may emit a pheromone (Hirsch, 1998). Along either side of the

9

vestibule lie the bulbi vestibuli which consist of a network of veins

surrounded by fibrous tissue (Gray, 1966).

Normal sexual functioning is dependent upon rich sensory

innervation (discussed previously), genital muscles, and an extensive

vascular network. The genital muscles, also known as the pelvic floor

muscles, include the bulbocavernosus and the ischiocavernosus muscles.

The bulbocavernosus muscle helps to maintain the structure of the pelvic

viscera and also serves as a vaginal sphincter. The ischiocavernosus

muscle acts to drive blood into the corpus cavernosum of the clitoris

(Stedman’s Medical Dictionary, 1995).

Masters and Johnson (1966) reported that the principal component

of sexual arousal in both men and women is vasocongestion of the

genitals. Sexual arousal in women results in vasocongestion of the

vagina, vulva, clitoris, uterus, and possibly the urethra (Grafenberg, 1950)

that is 2 to 3 times greater than when a women is not sexually aroused

(Geer & Quartararo, 1976; Wagner & Ottesen, 1980). Sexual stimulation

produces an increase in vasocongestion within 2-4 seconds (Gillian &

Brindley, 1979). This response is greater the more proximal to the vaginal

orifice. That is, the response is lessened, in descending order, on the

anterior wall, the lateral walls, and the posterior wall of the vagina. This

10

increase in blood flow produces a pattern of temperature increase similar

to the vascular response, although the time course is slower (Gillian &

Brindley, 1979).

Genital vasocongestion occurs via the iliac artery. The iliac artery

supplies the genital region through the uterine artery, the vaginal artery,

and the pudendal artery branch. The vaginal vascular network is located

in the middle layer of the vaginal wall although some blood vessels are

located within the inner mucous layer and the outer fibrous layer (Gray,

1966). Vaginal lubrication during sexual arousal results from

vasocongestion of the vaginal capillaries. As the blood flow increases, the

blood vessels become engorged with blood and this causes the pressure

within the capillaries to increase. Some fluid from within the capillaries

leaks out of the vessels into the interstitial space. This is typical in all

bodily tissue, but during sexual arousal the fluid is not reabsorbed by the

surrounding cells as quickly as it emerges. As a result, the fluid passes

between the cells of the vaginal epithelium and emerges on the vaginal

wall as sweat-like droplets. These droplets can quickly build up to form a

lubricating film that facilitates smooth penetration of the penis (Levin,

1992).

11

Patterns of vasocongestion may change during orgasm. Vaginal

blood volume (VBV) drops dramatically during orgasm and then returns,

after orgasm, to approximately half that of pre-orgasm levels. In addition,

for at least 10 minutes post-orgasm, VBV and vaginal pulse amplitude

(VPA, a measure of moment to moment changes in vasocongestion;

Rosen & Beck, 1988) remain elevated above baseline levels (Geer &

Quartararo, 1976). Such changes in vasocongestion may be the result of

smooth muscle contraction. Orgasm, in women, involves contractions in

the smooth muscles of the genital region which are characterized by

rhythmic, synchronized vaginal, anal (Bohlen, Held, Sanderson, &

Ahlgren, 1982), and uterine (Chayen, Tejani, Verma, & Gordon, 1986;

Fox, 1976) contractions. Clitoral stimulation produces a tonic contraction

of the pelvic floor muscles that differs from the phasic pelvic floor

contractions seen during orgasm but that may nonetheless be part of

normal sexual arousal. These tonic contractions may in fact be necessary

for normal sexual responses; 2 of 10 women examined did not show this

reflex and both were anorgasmic (Gillian & Brindley, 1979).

1.4 Tactile Sensitivity and the Sexual Response Cycle

Presumably, sexual arousal can be produced and facilitated by

each of the five senses though it is arguably most dependent upon the

12

sense of touch. Indeed, sensate-focus, which is one of the most widely

practiced sex therapy techniques, involves attending to and touching

erogenous zones (Kaplan & Passalacque, 1987). Moreover, sexual

functioning is not affected in blind and deaf individuals (Hakim-Elahi, 1982)

but is impaired when conscious perception of tactile sensation is

diminished or completely lost (e.g., Dixson, 1986; Sipski, Alexander, &

Rosen, 1995a, b). When lidocaine (a topical anesthetic) was applied to

the vagina of female marmosets, they demonstrated a decrease in

behaviors typically seen during intromission such as head turning, mouth

opening, and body struggling (Dixson, 1986). Similarly, when applied to

the penises of male rabbits, intromission latency was delayed, and

ejaculation was absent or delayed (Agmo, 1976); in male marmosets

intromission latency, but not ejaculation was also delayed (Dixson, 1986).

Thus, in animals, sexual functioning is impaired when normal tactile

sensations are disrupted.

Human data also suggest that conscious perception of tactile

sensation is important for normal sexual functioning to occur. Women with

spinal cord injuries can become sexually aroused and can have orgasms

suggesting that some aspects of arousal and orgasm are mediated at the

level of the spinal cord. The sexual functioning of spinal-cord-injured

13

women is impaired compared to normal women, however. When

compared to women with intact spinal cords, women with complete spinal

cord injuries did not demonstrate psychophysiological arousal when

viewing erotic videos, but both spinal-cord-injured women and normal

women evidenced increased VPA with manual stimulation. The spinal-

cord-injured women reported subjective arousal when watching the erotic

video even though they did not evidence increased VPA (Sipski,

Alexander, & Rosen, 1995b). Similarly, approximately 50% of women with

complete spinal cord injuries were able to achieve orgasm with manual

stimulation although those that were able to achieve orgasm took

significantly longer to do so compared to women with intact spinal cords

(Sipski et al., 1995a). Thus, conscious perception of tactile stimulation

may not be required for orgasm although it may permit orgasm to occur

more rapidly.

Factors that affect sexual functioning have also been shown to

affect tactile sensitivity. For example, normal estrogen levels are required

to produce adequate vaginal lubrication (Bachmann, 1995) and estrogen

treatment may also affect tactile sensitivity. Estrogen-treated female rats

had larger pudendal nerve receptive fields (Kow & Pfaff, 1973) and facial

trigeminal nerve receptive fields (Bereiter & Barker, 1975) compared to

14

non-treated rats. In rats and canaries, estrogen treatment increased

tactile sensitivity (Bereiter & Barker, 1975; Hinde & Steele, 1964; Kow &

Pfaff, 1973) although, in one study examining rats, estrogen treatment

decreased tactile sensitivity (Bereiter, Stanford, & Barker, 1980). In

addition, estrogen treatment affected RA receptors but did not affect SA

receptors (Kow & Pfaff, 1973). Although estrogen treatment produced a

thickening of the skin, the skin was equally distendable in estrogen-treated

animals as in non-treated animals (Bereiter et al., 1980) suggesting that

decreased tactile sensitivity is not likely due to the skin being less flexible.

Several studies suggest that activation of the sympathetic branch of

the autonomic nervous system facilitates sexual arousal in women

(Meston & Gorzalka, 1995, 1996a, 1996b). Studies also indicate that

tactile sensitivity may be affected indirectly through modulation of the

sympathetic nervous system although the direction of effect is somewhat

contradictory across studies. That is, two studies report that sympathetic

activation increases tactile sensitivity in the frog (Chernetski, 1963;

Loewenstein, 1956) while one reported that it decreases tactile sensitivity

in the cat (Pierce & Roberts, 1981). It is not clear how to generalize such

findings to humans. The one study that did examine humans found that

sympathetic blockade (stellate ganglion or differential epidural anesthetic)

15

increased tactile sensitivity (Kissin, McDanal, Brown, Xavier, & Bradley,

1987) which suggests that sympathetic activation in humans decreases

tactile sensitivity. The underlying mechanism by which sympathetic

activation affects tactile sensitivity may be complex. In the rat, chemical

sympathectomy produced increased sensitivity in RA hair receptors while

surgical sympathectomy produced decreased sensitivity in RA and SA

receptors sensitive to skin displacement (Bereiter et al., 1980). If different

methods of sympathetic blockade result in increased and decreased

tactile sensitivity in animals, it is possible that the same may be true in

humans.

Some evidence suggests that tactile sensitivity may be closely tied

to vascular mechanisms. Hypertensive (people with high blood pressure)

individuals were found to have nearly three times the tactile threshold and

nearly two times the pain threshold as compared to non-hypertensive

individuals. This was true for individuals in their 20’s, 30’s, and 40’s

(Zamir & Shuber, 1980). Furthermore, borderline hypertensive individuals

displayed a similar, though less marked, increase in tactile and pain

thresholds (Rosa, Ghione, Panattoni, Mezzasalma, & Giuliano, 1986). A

similar relationship between blood pressure and pain perception has been

demonstrated in rats which suggests that sensory perception may be

16

affected by hypertension in other mammals as well (Maixner, Touw,

Brody, Gebhart, & Long, 1982). The mechanism connecting tactile

sensitivity and vascular functions is not clear, however. When

hypertension was induced in rats, the rats demonstrated an increase in

pain threshold that was reversed by the opiate antagonist, naloxone. This

effect could not be accounted for by a motor deficit or damage to pain

nerves (Zamir & Segal, 1978). Instead, the baroreceptor, which is a blood

pressure feedback mechanism, was implicated in this process (Zamir &

Maixner, 1986).

The above evidence suggests that tactile sensitivity is affected by

mechanisms underlying sexual functioning although the exact relationship

is unclear. These mechanisms may affect tactile sensitivity, and in turn,

changes in tactile sensitivity may produce sexual difficulties. Alternatively,

bodily mechanisms may affect both tactile sensitivity and sexual

functioning independently without tactile sensitivity exerting a direct

influence on sexual functioning. Several studies have examined tactile

sensitivity in men with sexual difficulties and found that men with erectile

difficulties had decreased sensitivity (Morrissette, Goldstein, Raskin, &

Rowland, 1999; Rowland, Haensel, Blom, & Slob, 1993; Rowland,

Leentvaar, Blom, & Slob, 1991). Conflicting evidence has been found in

17

men with premature ejaculation; one study found that men with premature

ejaculation showed higher levels of tactile sensitivity than did men with

normal ejaculation latencies (Xin, Chung, Choi, Seong, Choi, & Choi,

1996), while another study found no difference between men with

premature ejaculation and men with normal ejaculation latencies (Rowland

et al., 1993). To my knowledge, no studies have been published

examining tactile sensitivity in women with sexual difficulties.

Although a paucity of research exists on the relation between tactile

sensitivity and sexual function, the above review provides evidence that

tactile sensitivity may be important for sexual arousal and orgasm, and

suggests that variation in tactile sensitivity may result in sexual arousal

and orgasm difficulties. The present investigation will provide the first

empirical examination of tactile sensitivity in women with sexual desire,

arousal, and orgasm difficulties and will compare results with those of

women reporting no sexual difficulties. Specific hypotheses will be

discussed in chapter 2.

1.5 Tactile Sensitivity and Sexual Dysfunction: Role of Serotonin

If tactile sensitivity plays a role in sexual functioning, it is possible that

the mechanisms of action involve serotonin. A substantial body of evidence

suggests that serotonin (which is also referred to by its chemical symbol, 5-

18

HT) plays an important role in tactile sensitivity and in sexual functioning.

Although serotonin is best known as a neurotransmitter in the central nervous

system, approximately 95% of serotonin receptors are located in the

periphery of the body (Prichard & Smith, 1990). Serotonin is involved in a

wide variety of peripheral processes including vascular and non-vascular

smooth muscle contraction, autonomic and sensory neurotransmission,

endocrine and exocrine secretion, and carotid body and cardiopulmonary

reflexes (complete description of serotonin’s role in peripheral mechanisms is

beyond the scope of this paper; for a thorough review of serotonin in the

periphery, see Fozard, 1989). Serotonin may affect tactile sensation directly

by acting as a neurotransmitter in the spinal cord and on peripheral nerves or

by acting indirectly on, for example, the vascular system. Normal sexual

functioning is dependent upon normal nervous, muscular and vascular

functioning (Masters & Johnson, 1966) and thus it is possible that serotonin

may act on one or all of these systems to produce directly or indirectly

changes in tactile sensation and sexual functioning. The second portion of

this paper will discuss research examining serotonin in peripheral processes

likely to affect sexual functioning.

1.5.1 Serotonin in the Female Genital Tract

19

Serotonin is typically synthesized and stored in the tissue in which it

is later used (Skop & Brown, 1996). Animal and human studies suggest

that certain areas within the female genital tract contain serotonin. In

female mongrel dogs, serotonin was found in paraneurons (cells located

adjacent to nerve cells) of the distal and middle urethra. The cells were in

the greatest density in the central portion of the urethra and none were

found in the bladder and lower urethra (Hanyu, Iwanaga, Kano, & Fujita,

1987). It is of note that stimulation to this region of the urethra may

facilitate sexual arousal (Grafenberg, 1950). Biopsies of human fallopian

tubes and ovaries have not revealed serotonin-containing cells (Fetissof,

Gerger, Dubois, Arbeille-Brassart, Lansac, Sam-Giao, & Jobard, 1985).

Biopsies from human endometrium suggest that normal uterine cells do

not contain serotonin. Biopsies of tumors of the endometrium, however,

have revealed serotonin-containing cells which suggests that serotonin

may take part in abnormal cell proliferation (Fetissof et al., 1985).

Serotonin-containing cells have also been found in human biopsies of the

cervix and in tumors of the cervix (Fetissof et al., 1985). While serotonin-

containing cells have been found in the rabbit vagina (Forsberg,

Rosengren, & Sjoberg, 1964), very few have been detected in the canine

vagina (Hanyu et al., 1987). Serotonin cells have been found in the

20

external genitalia of female animals. Specifically, they were found in the

vaginal-vestibular junction and the clitoris of dogs (Hanyu et al., 1987) and

in the vestibular epithelium of rabbits (Forsberg et al., 1964). In humans,

serotonin-containing cells have also been found in biopsies of the vulva.

They were most frequently found in the epithelium of Bartholin’s glands,

which are located on either side of the vaginal orifice (Fetissof et al.,

1985). Thus, in general, serotonin-containing cells may be located in

regions of the genitalia that receive direct tactile stimulation during sexual

activity, and when they are found in genital regions that do not receive

direct stimulation, the cells may be part of abnormal cell proliferation.

1.5.2 Serotonin and Non-Vascular Smooth Muscle Contraction

Serotonin may affect sexual functioning by acting on the muscular

system. As discussed previously, orgasm involves contraction of genital

smooth muscles, and serotonin is involved in smooth muscle contractions

in several areas of the body including the genito-urinary system. In the

urinary system, in animals (rabbit, cat, pig) as well as humans, 5-HT

produces initial rapid contractions of the bladder followed by tonic

contractions. In the cat, 5-HT acts on the 5-HT3 receptor to produce the

rapid contractions and on the 5-HT2 receptor for tonic contractions. In

21

humans, it has been shown that 5-HT2 antagonists can block a portion of

this latter contraction (Cohen, Schenck, Colbert, & Wittenauer, 1985).

Serotonin produces contractions in the rat and human uterus. The

5-HT2 antagonists, LY53,857 and ketanserin, inhibited 5-HT induced

contractions of the rat uterus in vitro (Cohen et al., 1985; Cohen &

Wittenauer, 1987). Similarly, serotonin produced contractions in human

myometrial smooth muscle harvested from women undergoing cesarean

section and it was a more potent contractile agent than norepinephrine,

prostaglandin F2α and prostaglandin E2 (Maigaard, Forman, & Anderson,

1986). No clear relationship was found, however, between placentas of

women who did, and did not, experience uterine contractions during

delivery and 5-HT (Szukiewicz, Maslinska, Stelmachow, & Wojtecka-

Lukasik, 1995).

22

1.5.3 Serotonin and Endocrine Functions

Evidence suggests that both central and peripheral serotonin

affects the levels of some neuromodulators and hormones. While

centrally administered 5-HT caused an increase in vasopressin release in

male rats, this release was attenuated with xylamidine, a 5-HT2a

antagonist that does not cross the blood-brain barrier (Pergola, Sved,

Voogt, & Alper, 1993). Similarly, in male rats, peripheral administration of

the 5-HT2a agonist DOI, produced increased adrenocortical secretion.

Central administration produced a similar effect suggesting that

adrenocortical secretions are mediated by both central and peripheral 5-

HT2a receptors (Welch & Saphier, 1994). It is possible, though, that the

effects found after peripheral administration were due solely to DOI’s

central effects since the compound is able to cross the blood-brain barrier.

In addition, corticosterone secretion, in male rats, was increased by

peripheral administration of the 5-HT2a agonist DOI and this effect was

attenuated by the peripheral 5-HT2a antagonist, xylamidine (Alper, 1990).

Moreover, peripheral corticosterone administration produced increased

receptive and proceptive behaviors in female rats and this effect was

antagonized by the serotonin reuptake inhibitor and 5-HT2a antagonist,

nefazodone (Hanson, Gorzalka, & Brotto, 1998). No clear relationship has

23

been found between VPA or VBV and estradiol, progesterone, prolactin,

cortisol, luteinizing hormone, or testosterone. Prolactin may be related to

subjective arousal in women, however (Schreiner-Engel, Schiavi, Smith, &

White, 1981; Heiman, Rowland, Hatch, & Gladue, 1991).

Peripheral serotonin levels fluctuate during the menstrual cycle.

During the midluteal, late luteal, and premenstrual phases, serotonin

levels increase, and during the menstrual and follicular phases they

decrease (Rapkin, Edelmuth, Chang, Reading, McGuire, & Su, 1987;

Tam, Chan, & Lee, 1985). In platelet-poor plasma, serotonin levels were

lowest during the ovulatory phase (Blum, Nessiel, David, Graff, Harsat,

Weissglas, Gabbay, Sulkes, Yerushalmy, & Vered, 1992). Serotonin may

play a role in VPA changes throughout the menstrual cycle; VPA was

highest and remained at a criterion level longest during the luteal phase of

the menstrual cycle (Schreiner-Engel et al., 1981). Thus, both serotonin

and VPA seem to be highest during the luteal phase of the menstrual

cycle suggesting that serotonin mechanisms and VPA mechanisms may

be related. To my knowledge, however, no researchers have examined

the effect of serotonin on VPA.

Women with premenstrual syndrome, which is characterized by

several difficulties associated with central serotonin disregulation

24

(headache, depression), have cyclical fluctuations in peripheral serotonin

that differs from that seen in women without premenstrual syndrome. In

women with premenstrual syndrome, peripheral serotonin levels, but not

estradiol or progesterone levels, were lower throughout the cycle and did

not show the typical increase during the luteal and premenstrual phases.

Indeed, in some premenstrual syndrome women, serotonin levels

decreased slightly during these phases (Rapkin et al., 1987). In addition,

women reporting premenstrual dysphoria who were taking fluoxetine, a

serotonin reuptake inhibitor, experienced changes in the length of their

menstrual cycle (in some cases shortened and in some cases

lengthened). Such changes were more often noted in women taking

higher doses (Steiner, Lamont, Steinberg, Stewart, Reid, & Streiner,

1997).

It is not clear whether menstrual changes in peripheral serotonin

could affect tactile sensitivity and sexual functioning. Although it is

somewhat controversial, some evidence suggests that sexual functions,

such as desire, fluctuate across the cycle in that non-significant increases

in desire have been reported during the luteal and follicular phases of the

menstrual cycle (Schreiner-Engel et al., 1981), when serotonin levels were

presumably high and low, respectively.

25

1.5.4 Serotonin and Vascular Mechanisms

Serotonin may affect tactile sensitivity directly or indirectly by its effect

on vascular functioning. As discussed earlier, animals and humans with

hypertension have reduced tactile sensitivity, suggesting that tactile sensitivity

may be influenced by vascular mechanisms (Maixner et al., 1982; Rosa et al.,

1986; Zamir & Shuber, 1980). In addition, during sexual arousal, the

vasculature of the genitals becomes engorged with blood (Henson, Rubin, &

Henson, 1982) which Masters and Johnson (1966) characterized as being the

primary component of sexual arousal. It is possible that serotonin’s

vasoactive properties affect tactile sensitivity and sexual functioning as the

majority of peripheral serotonin is stored in blood platelets. Serotonin is

synthesized in the enterochromaffin cells of the gastrointestinal tract and then

released into the blood stream where it is taken up by platelets. Serotonin

that is not taken up by platelets is either metabolized in the liver by

monoamine oxidase or by the pulmonary vascular endothelium. Serotonin

that is stored in platelets can later be released to act on vascular functions.

Indeed, one of serotonin’s primary functions is the regulation of vascular tone

and blood flow (Skop & Brown, 1996).

26

Serotonin's role in the regulation of blood flow is complicated

because it is involved in both vasodilation and vasoconstriction.

Depending on several factors, when animal and human arteries are

exposed to serotonin, serotonin agonists, serotonin antagonists, and

platelets, either vasoconstriction or vasodilation can result. Evidence

suggests that serotonin produces vasoconstriction by acting primarily on

the 5-HT2A receptor (e.g., Yang & Mehta, 1994; an exception, however,

found that serotonin-induced vasoconstriction did not seem to be

mediated by the 5-HT2A receptor (Koch, Alsip, Feige, Wead, & Harris,

(1994)). Rat arteries exposed to blood platelets either constricted or

dilated but the contractile effect was abolished by the 5-HT2A antagonist,

LY 53, 857 (Yang & Mehta, 1994). In male rats, DOI, a 5-HT2A agonist,

when administered to peripheral receptors alone, caused vasoconstriction

and subsequently increased arterial pressure. When xylamidine, a 5-HT2A

antagonist that does not cross the blood brain barrier, was administered in

conjunction with DOI, arterial pressure did not increase (Dedeoglu &

Fisher, 1991). Taken together, this suggests that serotonin acts on the 5-

HT2A receptor to produce vasoconstriction.

Serotonin can affect blood pressure through both central and

peripheral receptors. Both central and peripheral administrations of DOI

27

lead to increased blood pressure but central DOI administrations appear

to increase blood pressure more rapidly (Fuller, Kurz, Mason, & Cohen,

1986; Rittenhouse, Bakkum, & Van de Kar, 1991). Small doses of

serotonin have not been shown to produce detectable increases in arterial

pressure (Kushiro, Kurumatani, Ishii, Yokoyama, Koike, Hatayama,

Kobayashi, & Kajiwara, 1988).

Evidence suggests that to produce vasodilation, serotonin acts on

the 5-HT1 receptor, and to a lesser degree, the 5-HT3 receptor (Skop &

Brown, 1996). When the 5-HT1 receptor is activated, it stimulates the

release of nitric oxide which is produced by the endothelium and causes

vasodilation (Luscher, Richard, Tschudi, & Yang, 1990). Consistent with

this finding, nitric oxide inhibitors, such as L-NNA and L-NMMA,

attenuated serotonin-induced vasodilation in the rat uterus (Saha, Alsip,

Henzel, & Asher, 1998) and enhanced serotonin-induced vasoconstriction

in male and female arteries (Capelli-Bigazzi, Nuno, & Lamping, 1991). In

some tissues, however, serotonin-produced vasodilation does not appear

to be mediated by the nitric oxide system (Alsip & Harris, 1992).

Nonetheless, several other substances, such as prostacyclins and

endothelium-derived hyperpolarizing factor can produce vasodilation

28

(Vanhoutte, 1997), and it is possible that serotonin may activate these

substances in some cases.

Several other factors influence whether serotonin produces

vasoconstriction or vasodilation. A particular artery may constrict or dilate

when exposed to serotonin depending upon whether it was relaxed or

constricted prior to serotonin exposure (Yang & Mehta, 1994). In addition,

serotonin may produce vasoconstriction or vasodilation depending upon

the size of the arterioles or venules. In general, larger blood vessels tend

to constrict when exposed to serotonin while small blood vessels tend to

dilate. In vitro studies of the rat cremaster muscle (a skeletal muscle

attaching the testicles to the body) reveal that arterioles between 3 µm

and 25 µm dilated when exposed to serotonin while arterioles between 78

µm to 121 µm in diameter constricted when exposed to serotonin (Alsip &

Harris, 1992; Wilmoth, Harris, & Miller, 1984). In vitro studies suggest that

small arterioles in the rat uterus also dilate in response to serotonin (Alsip,

Hornung, Saha, Hill, & Asher, 1996; Saha et al., 1998). Similarly, in vivo

studies reveal that rat cremaster arterioles between 70 µm and 120 µm

constricted to serotonin (Koch et al., 1994) and in male and female dogs,

large coronary arteries of approximately 2000 µm constricted in response

to serotonin (Cappelli-Bigazzi et al., 1991). The differential response

29

between large and small arterioles could be explained by the relative

proportion of specific serotonin receptors. In other words, it is possible

that large arterioles have a large proportion of 5-HT2A receptors relative to

5-HT1 receptors while smaller arterioles contain the reverse. Furthermore,

serotonin may affect large and small venules differently from large and

small arterioles. Large venules between 115 µm and 196 µm did not

respond to serotonin even at high levels of concentration (Wilmoth et al.,

1984). In another study, where the size of the veins was not reported,

human hand vein contracted when exposed to 5-HT as well as the 5-HT1-

like, 5-HT2, and 5-HT3 receptor agonists in vitro (Bodelsson, Tornebrandt,

Bertilsson, & Arneklo-Nobin, 1992). In rabbits, intravenous injections of 5-

HT produced increased blood flow to the stomach, heart, and brain but not

to the skin, lungs, and kidney. In rats, intraperitoneal injections produced

greater blood flow in muscles, lungs, heart, and brain but not the skin and

kidneys, although intravenous injection produced some increased blood

flow to the skin (Dabire, Cherqui, Safar, & Schmitt, 1990). Serotonin’s

differential vasoactive effect on small and large arterioles and venules

could account for serotonon’s effect on blood flow into various bodily

regions.

30

Other vaso-active substances can influence vascular tone, and

serotonin can act synergistically with such substances to affect

vasoconstriction and dilation. For example, the neurotransmitter and

neuromodulator, norepinephrine, and the endothelium-derived constriction

factor, endothelin, both potentiate the contractile effects of serotonin

(Yang & Mehta, 1994; Luscher et al., 1990; Yanagisawa, Kurihara,

Kimura, Tomobe, Kobayashi, Mitsui, Yazaki, Goto, & Masaki, 1988). In

addition, serotonin receptors may become sensitized by exposure to

vasoconstrictor agents such that previously “silent” serotonin receptors

become active (Yildiz, Smith, & Purdy, 1998).

Thus, serotonin acts on 5-HT1 and 5-HT2A receptors to regulate

vascular tone. Disruption to this delicate balance can lead to

abnormalities in vascular tone. For example, some vascular diseases

result in damage to the cells lining the blood vessels, known as the

endothelium, and this process can be studied in laboratories by artificially

removing the endothelium and examining how the blood vessels respond

to stimulation. When the endothelium is intact, precontracted male rat

aortic rings (i.e., sliced artery samples) dilated when exposed to 5-HT (via

platelets); when the endothelium was removed, the aortic rings contracted.

Furthermore, relaxed aortic rings with intact endothelium contracted

31

slightly when exposed to 5-HT, while denuded endothelium markedly

contracted (Yang & Mehta, 1994). Because nitric oxide is produced in the

endothelium, and because serotonin acts on the 5-HT1 receptor to release

nitric oxide and produce vasodilation, damage to the endothelium is likely

to disrupt this process. Thus, when the endothelium is damaged,

vasodilation processes may be disrupted while vasoconstriction processes

may continue normally. In such a situation, the delicate balance of

constriction and dilation is disrupted by serotonin administration which

produces vasoconstriction only (Skop & Brown, 1996).

In summary, serotonin in a powerful vasoactive agent. It is well

established that the genitals contain a rich vascular plexus and normal

sexual arousal involves vasocongestion of this tissue. In addition, several

studies have found a correlation between vascular functioning (blood

pressure) and tactile sensitivity (Maixner et al., 1982; Rosa et al., 1986;

Zamir & Shuber, 1980). It is possible that serotonin may act on vascular

mechanisms to affect sexual functioning and tactile sensitivity. Sexual

functioning is clearly dependent upon vascular functioning but the

relationship between vascular functioning and tactile sensitivity is not

clear. It is possible that vasodilation and vasoconstriction of capillaries

supplying tactile receptors could affect receptor sensitivity. Alternatively, it

32

is possible that serotonin could stimulate the vascular endothelium to

release a substance that directly or indirectly affects tactile receptors.

Additional evidence is needed before the relationship can be fully

understood.

1.5.5 Serotonin in the Spinal Cord and Peripheral Nerves

Serotonin receptors are also widely distributed in nerves of several

systems likely to affect sexual functioning indirectly or directly. An

autoradiographic mapping study of the rat spinal cord revealed a variety of

serotonin receptors subtypes. The distribution of serotonin receptors in

the spinal cord suggests that serotonin is involved in modulation of

autonomic functions and in relaying nociceptive information. The 5-HT1

and 5-HT1A receptors were found in the dorsal horn which relays

nociceptive information while the 5-HT1B receptor was found in many

regions of the spinal cord (Marlier, Teilhac, Cerruti, & Privat, 1991).

Serotonin receptors that may affect tactile sensitivity indirectly are

located in the motor neurons and in the sympathetic and parasympathetic

nervous systems. Serotonin receptors are located in motor nerve cell

bodies and when stimulated, cause excitation of the cell. Serotonin

33

receptors in the sympathetic and parasympathetic system are involved in

both excitation and inhibition (Fozard, 1984).

Serotonin receptors are located in the nerves that innervate sexual

organs. The rat hypogastric nerve, which innervates the uterus,

responded to serotonin stimulation, but less intensely than the pelvic

nerve, which innervates the vagina (Berkley, Robbins, & Sato, 1993).

Nerve fibers innervating the vasculature of the oviduct and uterine horn,

have been shown to contain serotonin (Amenta, Vega, Ricci, & Collier,

1992). The rat hypogastric nerve innervates the cervix (Berkley et al.,

1993) and serotonin has been found in the nerve fibers which innervate

the cervical vasculature (Amenta et al., 1992).

Serotonin may affect the cutaneous free nerve endings and

mechanoreceptors. The 5-HT2A receptor was found on 32% of the axons

in the glabrous (hairless) skin of the rat. In particular, receptors were

found in free nerve endings and in the Pc corpuscle (Carlton &

Coggeshall, 1997). In the cat, serotonin excited cutaneous afferent fibers

of slowly adapting pressure receptors, produced a weak response in free

nerve cells and thermoreceptors, and produced no response in hair

receptors (Fjallbrant & Iggo, 1961). In addition, evidence suggests that

serotonin is a hyperalgesic. When injected into the paw of the rat,

34

serotonin produced behavior indicative of hyperalgesia (increased

sensitivity to normal stimulation and painful stimulation). Indeed, it has

been suggested that serotonin antagonists may be useful in the treatment

of pain (Hong & Abbott, 1994; Taiwo & Levin, 1992).

1.5.6 Acute Versus Chronic Effects of Serotonin

It is important to distinguish between the acute and chronic effects

of serotonin. While acute agonism or antagonism of serotonin may

produce one result, chronic agonism or antagonism of serotonin may

produce sensitization or desensitization of serotonin receptors with results

very different from those found acutely. For example, in the rat, isamide, a

5-HT derivative, temporarily blocked 5-HT induced uterine contractions in

vitro. In subsequent administrations of 5-HT, the uterine 5-HT receptors

were more sensitive resulting in greater contraction (Huidobro-Toro,

Huidobro, & Ruiz, 1979). Multiple exposure to the 5-HT1A agonist, 8-OH-

DPAT, in vivo, resulted in a reduced contraction response when the uterus

was later exposed, in vitro, to 5-HT. No such down regulation was found

with 5-HT in vivo overexposure, however, suggesting that 5-HT1A agonism

resulted in down regulation of the 5-HT2 receptor (Helton & Colbert, 1994).

35

1.6 Selective Serotonin Reuptake Inhibitors, Sexual Dysfunction and

Tactile Sensitivity

Taken together, a large body of evidence indicates that serotonin

may be a potent agent in several mechanisms likely to affect sexual

functioning such as nervous, endocrine, muscular, and vascular

mechanisms. In addition, some evidence suggests that serotonin may

affect tactile sensation directly or indirectly. It is possible that sexual

difficulties arise from an over-sensitivity or under-sensitivity of tactile

receptors. It also is possible that sexual difficulties arise from abnormal

peripheral serotonin activity. Individuals with sexual difficulties may have

different tactile sensitivity compared to individuals with normal sexual

functioning and may also have different peripheral serotonin activity. In

addition, if peripheral serotonin activity changed in an individual who

previously experienced normal sexual functioning, tactile sensitivity may

also change and possibly result in sexual difficulties.

Indeed, antidepressants such as the monoamine oxidase inhibitors

(MAOIs), tricyclics, and selective serotonin uptake inhibitors (SSRIs) all

affect endogenous serotonin and all have been found to induce sexual

dysfunctions. The most typical sexual side effect of MAOIs and tricyclics

is impaired orgasmic function (Meston & Gorzalka, 1992). Sexual side

36

effects of SSRIs include, in both men and women, decreased libido,

difficulty achieving orgasm, and inability to reach orgasm. Depending

upon the study, between 2% - 75% of patients taking SSRIs, such as

fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and venlafaxine

(Effexor), report sexual side effects (Feiger, Kiev, Shrivastava, Wisselink,

& Wilcox, 1996; Meston & Gorzalka, 1992; Montejo-Gonzalez et al., 1997;

Patterson, 1993; Pearlstein, & Stone, 1994; Preskorn, 1995).

Interestingly, a literature review revealed that, in some cases, SSRIs

produce increases in sexual desire, and in one case, spontaneous orgasm

(Meston & Gorzalka, 1992). Reports indicate that sexual dysfunctions

induced by fluoxetine may be dose dependent, for both men and women,

such that higher doses are more likely to produce problems, and the

problems may be alleviated by lowering the dose (Benazzi & Mazzoli,

1994; Patterson, 1993).

A literature review by Meston and Gorzalka (1992) suggested that

males are more likely than females to experience sexual side effects from

antidepressants, such as MAO inhibitors and tricyclics, although it is

possible that men are simply more willing to report such problems.

Indeed, a study of 344 male and female outpatients, in which patients

answered questions regarding their sexual functioning, revealed that

37

sexual difficulties as a result of SSRIs were actually more severe for

females than males. The women who reported sexual difficulties reported

more severe loss of libido and greater difficulty achieving orgasm than did

the men reporting sexual difficulties (Montejo-Gonzalez et al., 1997).

Thus, antidepressants may affect men and women differently depending

upon the particular class of antidepressant, or the differences found may

simply reflect reporting bias in women. It is also possible, though, that

greater percentages of men experience sexual problems relating to

antidepressant use, but that the women who do experience problems

experience more severe difficulties.

One antidepressant, nefazadone, has a different mechanism of

action as compared to typical SSRIs and seems to produce fewer sexual

side effects (Preskorn, 1995; Robinson, Roberts, Smith, Stringfellow,

Kaplita, Seminara, & Marcus, 1996). Nefazadone, unlike the typical SSRI,

is a 5-HT2 receptor antagonist as well as a 5-HT reuptake inhibitor.

Chronic nefazadone use, like that of many typical SSRIs, produces a

down regulation of 5-HT2 receptors and a reduction in the number of 5-

HT2 receptors. Because of its unique mechanism of action, though,

chronic nefazadone use may produce an upregulation of 5-HT1A receptors

which may account for its antidepressant quality (Eison, Eison, Torrente,

38

Wright, & Yocca, 1990). It is not exactly clear why nefazadone produces

fewer sexual side effects compared to traditional SSRIs, but it is possible

that its 5-HT2 receptor antagonist property serves to prevent excessive

vasoconstriction, thus permitting normal genital vasocongestion following

sexual stimulation.

The finding that SSRIs can cause sexual difficulties is robust but

the mechanism has not been elucidated A previous review of the literature

suggests that chronic antidepressant use alters serotonin activity centrally

by altering receptor sensitivity, by decreasing the number of 5-HT2

receptors and, although the evidence is inconsistent, by decreasing the

number of 5-HT1 receptors (Meston & Gorzalka, 1992). In the periphery,

SSRIs block the uptake of 5-HT into the platelets (Stahl, 1985) and mast

cells (Purcell, Cohen, & Hanahoe, 1989; Rudolph, Oviedo, Vega,

Martinez, Reinicke, Villar & Villan, 1998) and impair the ability of the

pulmonary vasculature to remove 5-HT from the blood (Gershon &

Jonakait, 1979; Ortiz & Artigas, 1992; Wong, Horng, Bymaster, Hauser, &

Molloy, 1974). Acutely, SSRIs produce an increase in blood 5-HT (Paez &

Hernandez, 1996), and a decrease in platelet 5-HT in rats (Bourdeaux,

Desor, Lehr, Younos, & Capolaghi, 1998). Chronically, fluoxetine-use also

produces a decrease in platelet 5-HT (Bakish, Cavazzoni, Chudzik,

39

Ravindran, & Hrdina, 1997; Pigott, Pato, Bernstein, Grover, Hill, Tolliver, &

Murphy, 1990; Wagner, Montero, Martensson, Siwers, & Asberg, 1990),

but unlike acute fluoxetine use, chronic fluoxetine use produces a

decrease in whole blood 5-HT in both rats (Ortiz & Artigas, 1992) and

humans (Tyrer, Marshall, & Giffiths, 1990) indicating that 5-HT synthesis

may be down-regulated.

Chronic SSRI-use may produce a decrease in platelet and plasma

5-HT but it is not clear how this would affect sexual functioning. SSRIs

could act to alter 5-HT receptor density or sensitivity on peripheral nerves.

Serotonin is involved in nociception (Richardson, 1990) and a change in

the 5-HT receptor density or sensitivity could produce, depending upon

the direction of effect, either hyperalgesia or hypoalgesia. Acute

administration of the 5-HT reuptake inhibitors, zimeldine, fluoxetine, and

fluvoxamine, produced hyperalgesia in mice and rats (Dirksen, Van

Luijtelaar, & Van Rijn, 1998; Fasmer, Post, & Hole, 1987). In contrast,

anecdotal evidence suggests that chronic SSRI-use can produce vaginal

anesthesia (Ellison & DeLuca, 1998; King & Horowitz, 1993) and a study

of several thousand patients prescribed SSRIs revealed an increased

incidence of paresthesias, such as sensation disturbances and

hypoesthesia as compared to those administered placebo (Preskorn,

40

1995). Anesthesia from vaginal stimulation produces increased 5-HT

activity in the spinal cord (Crowley, Rodriguez-Sierra, & Komisaruk, 1977;

Steinman, Komisaruk, Yaksh, & Tyce, 1983;Whipple & Komisaruk, 1985).

If SSRIs alter 5-HT receptor density or sensitivity, SSRI-use may intensify

analgesia from vaginal stimulation that, in turn, may impair sexual

functioning.

Although reports of parasthesias associated with SSRI use are

fairly uncommon (Preskorn, 1995), it is possible that SSRIs produce

decreased tactile sensitivity that is detectable only through careful physical

exam but that is nonetheless sufficient enough to impair sexual

functioning. If so, reported cases of vaginal anesthesia may represent an

extreme on a continuum of SSRI-induced tactile desensitization.

41

CHAPTER 2: PRESENT STUDY


Disorder and Female Orgasm Disorder

Question 2.1a: Is tactile sensitivity associated with female sexual

dysfunction?

The female genitalia contains rich sensory innervation (Krantz, 1958;

Yamada, 1951) and it is possible that individual differences in sensory

innervation could lead to differences in sexual functioning. In addition,

several factors known to affect sexual functioning, such as estrogen levels

(e.g., Bachmann, 1995), sympathetic activation (e.g., Meston & Gorzalka,

1995), and hypertension (e.g., Bansal, 1988), have also been found to

affect tactile sensitivity (e.g., Bereiter & Barker, 1975; Chernetski, 1963;

Maixner et al., 1982). This is consistent with studies examining men which

have found that tactile sensitivity differs in men with sexual problems

compared to men who are functioning normally (e.g., Xin et al., 1996).

Prediction 2.1a: It is hypothesized women with Female Sexual Arousal

Disorder (FSAD) will differ in tactile sensitivity compared to sexually

functional women. Women with low estrogen levels often experience

reduced vaginal lubrication (Bachmann, 1995). Estrogen treatment is

42

associated with increased tactile sensitivity (e.g., Kow & Pfaff, 1973) which

suggests that reduced estrogen levels may be associated with decreased

tactile sensitivity. In addition, women with complete spinal cord injuries,

with manual stimulation, show increases in vaginal vasocongestion (as

measured by VPA), though the increases were not as substantial as those

found in women with intact spinal cords (Sipski et al., 1995a). The male

analog to female sexual arousal disorder, erectile dysfunction, is

associated with reduced finger and penile tactile sensitivity (e.g., Rowland

et al., 1993). Finally, women with mild problems with sexual arousal had

less sensitive tactile sensation compared to normally functioning women

(Frohlich & Meston, 1999). Taken together, this suggests that women with

FSAD will have reduced tactile sensitivity compared to sexually functional

women.

Prediction 2.1b: It is hypothesized that women with Female Orgasmic

Disorder (FOD) will differ in tactile sensitivity compared to sexually

functional women. Depending on the study, sympathetic activation has

been found, in animals, to increase tactile sensitivity (e.g., Chernetski,

1963) and decrease tactile sensitivity (e.g., Pierce & Roberts, 1981).

Furthermore, evidence suggests that activation of the sympathetic branch

of the autonomic nervous system increases vaginal vasocongestion (as

43

measured by VPA) in sexually functional women but not in orgasmic

disordered women suggesting that women with orgasmic dysfunction may

differ physiologically from sexually functional women (Meston & Gorzalka,

1996a). It is possible that sympathetic activation affects tactile sensitivity

in anorgasmic women differently as well.

Research examining women with complete spinal cord injuries

suggests that tactile sensitivity may affect orgasmic functioning. Half of

women with spinal cord injuries are able to achieve orgasm with manual

stimulation, but take significantly longer than do women with intact spinal

cords (Sipski et al., 1995b). It is possible that women with orgasmic

dysfunction have tactile sensitivity that is sufficiently reduced to impair

orgasmic functioning.

Finally, previous studies examining men with premature ejaculation

suggest that tactile sensitivity may be increased in such men compared to

men with normal ejaculation latencies. To my knowledge, though, only

two such studies have been published. One found that men with

premature ejaculation had increased tactile sensitivity (Xin et al., 1996)

while the other found no difference between men with premature

ejaculation and men with normal ejaculation latencies (Rowland et al.,

1993). Taken together, the evidence suggests that women with FOD may

44

differ in tactile sensitivity from sexually functional women. It is not clear

whether orgasmic dysfunction women will have increased sensitivity,

decreased sensitivity, or whether some orgasmic dysfunction women will

have increased sensitivity while others will have decreased sensitivity.

Sympathetic nervous system activation studies (Meston & Gorzalka,

1996a; Meston & Gorzalka, 1996b) suggest that an optimal level of

sympathetic nervous system activation is associated with normal orgasmic

functioning, and that too little or too much sympathetic system activation

may be associated with FOD. It is possible that too little or too much

tactile sensitivity may be associated with FOD as well.


Question 2.1.2: Is severity of sexual dysfunction association with tactile

sensation?

To my knowledge, only one other study has examined tactile

sensitivity in women with sexual arousal problems, and this study

examined women with non-clinically diagnosed arousal problems (Frohlich

& Meston, 1999). These women had significantly higher tactile sensation

thresholds as compared to women with no sexual arousal complaints.

This suggests that tactile sensation is associated with even mild forms of

45

sexual dysfunction. It is possible that as the sexual problem becomes

more severe, the degree of cutaneous sensation impairment also

becomes more severe.

Prediction 2.1.2a: It is hypothesized that severity of arousal problems will

be associated with tactile sensation thresholds.

Prediction 2.1.2b: It is hypothesized that severity of orgasm problems will

be associated with tactile sensation thresholds.

2.2 Study 2: The Effect of Fluoxetine on Tactile Sensitivity and

Sexual Functioning

2.2.1 Analysis of Fluoxetine-Use and Tactile Sensitivity

Question 2.2.1a: Does fluoxetine treatment affect tactile sensitivity?

As discussed previously, serotonin is active in a variety of mechanisms

that are important in the sexual response cycle. Serotonin is active in

vascular smooth muscle contraction (e.g., Yang & Mehta, 1994) and

dilation (Skop & Brown, 1996), non-vascular smooth muscle contraction

(e.g., Cohen et al., 1985), endocrine functions (e.g., Hanson et al., 1998),

and in the spinal cord and in peripheral nerves (e.g., Carlton &

Coggeshall, 1997; Marlier et al., 1991). Several of these mechanisms

may affect tactile sensitivity as well. In particular, individuals with vascular

46

problems such as hypertension, have significantly decreased tactile

sensitivity (Zamir & Shuber, 1980) and it is possible that fluoxetine will

alter vascular functioning such that tactile sensitivity is indirectly affected.

Alternatively, fluoxetine may directly alter tactile sensitivity by acting on

cutaneous tactile receptors. Serotonin receptors have been found in the

glabrous (hairless) skin of the rat (Carlton & Coggeshall, 1997) and it is

possible that serotonin receptors are located in human skin as well.

Prediction 2.2.1a: It is hypothesized that fluoxetine treatment will produce

significant declines in tactile sensitivity.

Question 2.2.1b: At what time(s) following fluoxetine treatment initiation

does tactile sensitivity differ significantly from pre-drug levels?

SSRIs typically take several weeks before they affect depressive

symptoms (Meston & Gorzalka, 1992). It is possible that fluoxetine will

affect tactile sensitivity by acting on serotonergic mechanisms acutely. If

so, it would be expected that tactile sensitivity will differ at pre-drug

compared to week 1 post-drug initiation. It is also possible that fluoxetine

will affect tactile sensitivity by acting on similar mechanisms that produce

the antidepressant qualities of fluoxetine. If so, it would be expected that

tactile sensitivity at pre-drug will not differ compared to 1 week post-drug

initiation, but will differ compared to 3 weeks and 6 weeks post-drug

47

initiation. A previous study in men detected a significant change in

sensory threshold following one month fluoxetine treatment, but this study

did not examine sensory threshold at more acute phases of treatment

(Yilmaz, Tatlisen, Turan, Arman, & Ekmenkcioglu, 1999).

Prediction 2.2.1b: To determine whether changes in tactile sensitivity

occur immediately following fluoxetine treatment or only after chronic

fluoxetine treatment, exploratory .

Question 2.2.1c: Is there a relationship between fluoxetine dose and

tactile sensitivity threshold?

Acute serotonin administration produces physiological changes, in the rat,

that are positively associated with serotonin dose (Fuller et al., 1986).

Sexual side effects associated with SSRI use have also been shown to be

alleviated or reduced by lowering the prescription dose (Meston &

Gorzalka, 1992). Thus, it is possible that a significant correlation will exist

between tactile sensitivity and fluoxetine dose at week 1, week 3, and

week 6.

Prediction 2.2.1c: It is hypothesized that the change in tactile sensitivity

threshold will be significantly greater as fluoxetine dose increases.

2.2.2 Analysis of Fluoxetine-Induced Sexual Dysfunction

48

Manipulation Check: It is well documented that sexual dysfunction is a

common side effect of SSRIs (e.g., Meston & Gorzalka, 1992). Sexual

side effects associated with SSRIs include decreased libido, difficulty

achieving orgasm, and anorgasmia (Feiger et al., 1996; Meston &

Gorzalka, 1992; Montejo-Gonzalez et al., 1997; Patterson, 1993;

Pearlstein & Stone, 1994; Preskorn, 1995).

Prediction 2.2.1: It is therefore expected that fluoxetine-use will result in

decreased libido and orgasm difficulties.

2.2.3 Tactile Sensation as a Mediator of Fluoxetine-Induced Sexual

Dysfunction

Question 2.2.3: Does tactile sensation mediate fluoxetine-induced sexual

dysfunction?

To my knowledge, the hypothesis that tactile sensation mediates SSRI-

induced sexual dysfunction has not been previously examined. Yilmaz et

al. (1999) found that men receiving fluoxetine exhibited a significant

increase in penile sensory threshold and intravaginal ejaculation latency

following one month of medication treatment, but did not examine whether

tactile sensation mediated the delay in ejaculation.

49

Prediction 2.2.3: It is hypothesized that tactile sensation will mediate

fluoxetine-induced sexual dysfunction.

50

CHAPTER 3: METHOD


Disorder and Female Orgasmic Disorder

3.1.1 Overview of Experimental Design

The dependent variable was sexual functioning (Female Sexual

Arousal Disorder (FSAD), Female Orgasmic Disorder (FOD), normal

sexual functioning) and the independent variable was tactile sensitivity

(index finger sensation threshold, lip sensation threshold). In addition,

several variables that affect sexual functioning were measured and

analyzed as potential covariates.

3.1.2 Participants

Participants were 15 women with FSAD, 17 women with FOD, and

17 women who were functioning normally sexually. Participants were

recruited for the study from a pool of approximately 8000 male and female

students taking Introduction to Psychology courses (over a two year

period). A series of screening measures were used to identify women

who met DSM-IV-TR criteria for FSAD and FOD (American Psychiatric

51

Association, 2000), and to identify a group of normally functioning control

participants. Prospective participants were initially recruited using an

internet based prescreening if they indicated that they were female, 18

years or older, involved in a sexually active relationship, and not taking

antidepressant medication. Approximately 1300 participants met these

initial criteria.

Participants who met the initial screening criteria were invited to

participate in a questionnaire session at the Female Sexual

Psychophysiology Laboratory. This session was designed to identify

women who were likely to meet DSM-IV-TR criteria for FSAD, lifelong,

generalized type FOD, and women who were not experiencing sexual

problems. Three hundred and seventy-two participants attended the

questionnaire session. Participants provided written consent to participate

prior to completing the questionnaires.

3.1.2a Participant Selection: Questionnaires

Female Sexual Arousal Disorder (FSAD) Group: Arousal functioning was

measured using selected sections of an adapted version of the Sexual

Functioning Index (Taylor, Rosen, & Leiblum, 1994)(See Appendix H).

Participants who reported that they lacked vaginal lubrication 50-100% of

52

the time, over the last six months, were considered as potential FSAD

participants. This is consistent with the DSM-IV criteria that the participant

has a “persistent” problem with lack of vaginal lubrication.

Female Orgasmic Disorder (FOD) Group: Participants completed

selected portions of Orgasmic Functioning Questionnaire (OFQ) which

was designed to assess the participant’s ability to achieve orgasm

(Meston, Jung, Hanson, & Gorzalka, 1993) (see Appendix G).

Participants were asked to indicate the percentage of time specific

activities resulted in orgasm. Activities include “masturbation,” “manual

stimulation by partner,” “oral stimulation by partner,” “intercourse,” and

“intercourse & manual stimulation by self or partner.” For the present

study, orgasmic ability was defined as the highest percentage of time the

participant reached orgasm in any of the five situations. For example, if a

participant was able to achieve orgasm 90% of the time during

masturbation but was never been able to achieve orgasm in any of the

other situations, the participant would be designated as 90% orgasmic.

Thus, orgasmic ability was defined as the participant’s ability to achieve

orgasm given optimal (for each individual participant) conditions. This

scoring procedure has been used in previous research of this nature

53

(Meston & Gorzalka, 1996a; Meston, Gorzalka, & Wright, 1997).

Participants were selected as potential FOD participants if they report that

they had never achieved an orgasm in any of the five situations.

Normal Sexual Functioning Group: Women were selected as potential

control participants if they reported an absence of sexual difficulties.

Participants were included in this group if they obtained a Derogatis

Sexual Functioning Index (DSFI) Drive sub-test score within one standard

deviation of the mean (Derogatis, 1978) (see Appendix C), reported lack

of vaginal lubrication 0% of the time over the past month, lack of vaginal

lubrication less than 25% of the time over the past 6 months, obtained a

score of greater than or equal to 50% on the OFQ (indicating that in at

least one of the specified sexual activities they were orgasmic at least

50% of the time), and obtained Female Sexual Functioning Index (FSFI;

see Appendix D) domain (desire, arousal, lubrication, orgasm, pain,

satisfaction) and full scale scores within one standard deviation of the

mean of the FSFI normalization sample (Rosen, Brown, Heiman, Leiblum,

Meston, Shabsigh et al., 2000).

54

3.1.2b Participant Selection: Clinical Interview

Sixty-six women met the questionnaire criteria and participated in a

clinical interview. Prospective participants were interviewed by a clinical

psychology doctoral student with a Masters degree in clinical psychology.

The clinical interview was aimed at determining whether the participants

met DSM-IV-TR criteria for Hypoactive Sexual Desire Disorder, Sexual

Aversion Disorder, FSAD, FOD, Dyspareunia, or Vaginismus. Fifteen

participants met DSM-IV-TR criteria for FSAD, 17 for FOD, and 18

participants did not meet any DSM-IV-TR sexual dysfunction criteria.

Participants who did not meet criteria for any DSM-IV-TR sexual

dysfunctions were eligible for the control group. In addition, three

participants met criteria for both FSAD and FOD. Women with FOD often

report significant arousal problems (Meston, 2003), but since there was

not a sufficiently large sample size to constitute a separate duel diagnosis

group, these women were not included in statistical analyses.

The DSM-IV requires that factors such as life context and age must

be taken into account before a diagnosis is made. The participants in this

dissertation were all college students and thus any age related concerns

are likely to result from lack of sexual experience. Prior to the interview,

participants were excluded from the study if they indicated a level of

55

sexual experience (as measured by the DSFI Experience subtest) less

than a standard deviation below the mean for their age group. The DSM-

IV also requires that the participant report significant distress regarding

their sexual difficulty. All FSAD participants met this criteria, but two FOD

participants did not meet this criteria. The FOD participants were

nonetheless included in the final subject pool of this dissertation as this

diagnostic requirement is important for identifying participants who may be

interested in seeking treatment, but is not likely to reflect physical changes

that may be associated with FSAD or FOD. Since the purpose of this

dissertation was to identify potential physical characteristics associated

with FSAD and FOD, and not to identify participants who may be

interested in seeking treatment, these two FOD participants were not

excluded.

Finally, the DSM-IV requires that FSAD and FOD is not better

accounted for by another Axis I disorder or the use of a medication or

drug. Participants were excluded from the study if they reported Axis I

concerns that better accounted for their sexual problems and/or use of

medications known to cause sexual side-effects.

Twenty-four women met the questionnaire screening criteria for

FSAD, and of those, 15 met DSM-IV-TR criteria for FSAD. Four

56

participants were excluded as their arousal difficulties were subthreshold;

the arousal symptoms were not persistent or recurrent enough to qualify

as FSAD. One participant was excluded as her primary diagnosis was

hypoactive sexual desire disorder (HSDD), with some secondary arousal

difficulties. One participant was excluded as her primary diagnosis was

dyspareunia, with some secondary arousal difficulties. Three participants

were excluded as their primary diagnosis was FOD (specific, acquired),

with some secondary arousal difficulties. The final group of 15

participants met DSM-IV-TR criteria for FSAD, but previous studies

suggest that comorbidity of sexual concerns is high (e.g., Meston, 2003).

In this dissertation, of the 15 FSAD women, 5 reported decreased libido

(FSFI Desire domain one standard deviation below the mean of a

normative sample (Meston, 2003)), 6 reported orgasm difficulties (FSFI

Orgasm domain), and 12 reported sexual pain (FSFI Pain domain). Of the

final 15 FSAD participants, seven (46%) reported that they were using oral

contraceptives.

Twenty-four women met the questionnaire screening criteria for

FOD, and of those, 17 met DSM-IV-TR criteria for FOD. As mentioned

above, three of the 24 women were excluded as they met criteria for both

FSAD and FOD. Two women were excluded as they met criteria for FOD

57

specific acquired type, not FOD generalized life-long type. Two women

were excluded due to lack of sexual experience. Of the final 17 FOD

women, 7 reported decreased libido (FSFI Desire domain), 10 reported

decreased arousal (FSFI Arousal domain), 5 reported lubrication

difficulties (FSFI Lubrication domain), and 11 reported sexual pain (FSFI

pain domain). Of the final 17 FOD participants, nine (53%) reported that

they were using oral contraceptives.

Eighteen women met the questionnaire screening criteria for the

control group and the clinical interview confirmed that they did not meet

DSM-IV-TR criteria for any sexual disorders. All 18 control women fell

within one standard deviation of the mean on all domains of the FSFI

(Meston, 2003). One control subject was later excluded, however, as she

obtained a finger sensation threshold score of 72.3 mg, which was over

four standard deviations above the mean finger sensation threshold score

for the overall sample (overall sample mean = 23.30, SD = 11.84). Of the

final 17 control participants, 10 (58%) reported that they were using oral

contraceptives.

58

3.1.3 Covariates

Variables likely to be associated with sexual functioning were measured

for use as potential covariates in statistical analysis.

Blood Pressure and Pulse: Previous studies indicate that hypertension is

associated with sexual dysfunction (Bansal, 1988; Leiblum, Baume,

Croog, 1994). In addition, studies indicate that activation of the

sympathetic branch of the autonomic nervous, which results in increased

blood pressure and heart beat, facilitates sexual arousal in sexually

functional and dysfunctional women (e.g., Meston & Gorzalka, 1996a).

Thus, blood pressure and pulse were measured for potential use as

covariates in statistical analysis.

Drugs: Participants were excluded from the study if they indicated that

they were using prescription medications known to impair sexual

functioning (e.g., antidepressant medication). Participants were included,

however, if they reported drinking alcohol or smoking cigarettes, both of

which have been documented to affect sexual functioning (Crenshaw &

Goldberg, 1996; Huws & Sampson, 1993). Thus, degree of alcohol and

cigarette use will be measured for potential use as covariates in statistical

analysis.

59

Depression: It is well documented that depression is associated with

sexual dysfunction (e.g., Frohlich & Meston, 2002). Thus, degree of

depressive symptomology will be measured using the Beck Depression

Inventory (BDI) for potential use as a covariate in statistical analysis (Beck

& Beamesderfer, 1974).

Anxiety: Evidence suggests that anxiety and distraction secondary to

anxiety are associated with sexual dysfunction (Barlow, 1986). Thus,

degree of anxiety symptomology will be measured using the Beck Anxiety

Inventory (BAI) for potential use as a covariate in statistical analysis

(Beck, Epstein, Brown, & Steer, 1988).

Body Image: Body image dissatisfaction has been associated with sexual

problems (Jagstaidt, Golay, Pasini, 1996) and thus degree of body image

satisfaction will be measured using the Body Image Scale of the DSFI for

potential use as a covariate in statistical analysis (Derogatis, 1978).

Sexual satisfaction: It is possible that some participants will be

experiencing sexual difficulties as a result of dissatisfaction with the quality

of the sexual relationship. The Contentment, Communication, and

Compatibility domains of the Female Sexual Satisfaction Scale (FSSS;

Meston & Trapnell, 2001) were completed for potential use as covariates

in statistical analysis.

60

3.1.4 Measures

3.1.4a Self-Report Measures

Beck Depression Inventory (BDI): (see Appendix A) Depression was

measured with the BDI for use as a covariate in statistical analyses. The

BDI is a brief, 21-item, measure of depressive symptomology (Beck &

Beamesderfer, 1974).

Beck Anxiety Inventory (BAI): (see Appendix B) Anxiety was measured

using the BAI, which is a brief, 21 item measure of anxiety symptomology.

BAI score was measured for use as a covariate in statistical analysis

(Beck et al., 1988).

Derogatis Sexual Functioning Inventory (DSFI): (see Appendix C) All

participants will be administered the DSFI Experience sub-test and DSFI

Body Image sub-test. The DSFI Experience sub-test contains 24 items

(Derogatis, 1978). Each item contains statements regarding petting, oral

sex, intercourse, and masturbation. Participants indicate (yes/no) whether

they have ever engaged in that activity. Retest coefficients and internal

consistency coefficients for the DSFI Experience sub-test are .90

(Derogatis & Melisaratos, 1979). Content analysis of the DSFI Experience

sub-test indicates that a wider range of sexual behaviors is sampled by

61

this sub-test than comparable measures, and that this sub-test is both a

valid and reliable measure of sexual behavior (Andersen & Broffitt, 1988).

The Experience sub-test of the DSFI will be used to ensure that all

participants are sexually experienced, and that the two groups do not

differ significantly in sexual experience.

The Drive sub-test of the DSFI will be used to identify subjects for

the normally functioning group (Derogatis, 1978). On this sub-test,

subjects will be asked to report how frequently, over the past year, they

engaged in “intercourse,” “kissing and petting,” “masturbation,” “sexual

fantasies,” and subjects will be asked to report, “what would be your ideal

frequency of sexual intercourse?” Multiple choice options will include: 0

(not at all), 1 (once a month or less), 2 (1-2 times a month), 3 (once a

week), 4 (2-3 times a week), 5 (4-6 times a week), 6 (once a day), 7 (2-3

times a day), and 8 (4 or more times a day). Retest coefficients for the

drive sub-test is .77 (Derogatis & Melisaratos, 1979).

The DSFI Body Image Scale contains 22-items, although 10 items

pertain to general body image issues, six items to female only body image

issues, and six items to male only body image issues (Derogatis, 1978).

Female Sexual Functioning Index (FSFI): (see Appendix D) The FSFI is a

brief 19-item measure of female sexual functioning. It provides a total

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score as well as domain scores for desire, arousal, lubrication, orgasm,

satisfaction, and pain (Rosen et al., 2000). This measure will be used to

evaluate the sexual functioning of the participants. Normative data is

available for normally functioning women (Rosen et al., 2000), women with

FSAD (Rosen et al., 2000), and women with FOD (Meston, 2003).

Female Sexual Satisfaction Scale (FSSS): (see Appendix E) The

Contentment, Communication, and Compatibility Domains of the FSSS

(Meston & Trapnell, 2001) will be used to evaluate the sexual satisfaction

of the participants. Participants will be asked questions such as, “I often

feel my partner isn’t sensitive or aware enough about my sexual likes and

desires.” Multiple choice options will include: 1 (strongly disagree, 2

(disagree a little), 3 (neither agree nor disagree), 4 (agree a little), and 5

(strongly agree). The Contentment, Communication, and Compatibility

domains of the FSSS will be evaluated as potential covariates in statistical

analysis.

Medical Information Questionnaire: (see Appendix F) This measure was

developed for this dissertation. It includes items such as age,

antidepressant use, number of alcoholic beverages consumed per week,

and number of cigarettes smoked per week. Because it is possible that

63

alcohol and/or cigarette abuse could affect sexual functioning these

variables will also be used as covariates.

Orgasmic Functioning Questionnaire (OFQ): (see Appendix G)

Participants will complete selected portions of OFQ designed to assess

the participant’s ability to achieve orgasm (Meston et al., 1993).

Participants will be asked to indicate the percentage of time specific

activities result in orgasm. Activities include “masturbation,” “manual

stimulation by partner,” “oral stimulation by partner,” “intercourse,” and

“intercourse & manual stimulation by self or partner.”

Sexual Functioning Index (SFI): (see Appendix H) The Sexual Functioning

Index was adapted for the purposes of this dissertation (Taylor et al.,

1994). Participants will be asked to report how frequently, over the past

month and over the past six months, they have experienced “lack of

vaginal lubrication.” Multiple choice options include: 0 (not at all), 1

(seldom, less than 25% of the time), 2 (sometime, about 50% of the time),

3 (usually, about 75% of the time), and 4 (always). Participants will also

be asked to report the ejaculation latency of their partner. Multiple choice

options include: < 1 minute, 2-4 minutes, 5-7 minutes, 8-10 minutes, and

greater than 10 minutes. This item will be used to identify participants

64

who may be experiencing sexual difficulties as a result of inadequate

stimulation.

3.1.4b Physiological Measures

Tactile Sensitivity: Tactile sensitivity was measured using Von Frey

monofilaments on the distal portion of the index finger of the participant's

dominant hand and on the lower lip on the side of the lip corresponding to

the finger measurement (e.g., right index finger, right side of lower lip). A

Von Frey monofilament is a hair-like fiber that, when pressed against the

skin until the hair bends, applies a specific force. The amount of applied-

force depends upon the diameter and length of the hair. A pilot study

indicated that commercially available monofilaments were not sufficiently

sensitive to measure tactile sensation on the mouth, and for some

participants, on the fingers, and thus monofilaments were made and

calibrated in the laboratory. Monofilaments were made by gluing

polypropylene suture thread (Ethicon Prolene Sutures, Med-Vet

International, Illinois) to a commercially produced plastic monofilament

casing (a pen-like instrument; North Coast Medical, San Jose, CA) and

calibrated using an analytical balance (Eliav & Gracely, 1998). Based on

pilot testing, monofilaments applying 6, 8, 10, 20, 30, 40, and 80mg of

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force were used on the fingers, and monofilaments applying 2, 4, 6, 8, 10,

20, and 40mg of force were used on the lower lip.

Blood pressure: Blood pressure was measured using a digital blood

pressure cuff (Smith & Nephew, Inc.).

3.1.5 Procedure

Students who met the criteria for the study were scheduled for a

physical exam and additional questionnaire testing. All examiners were

female and were blind to the sexual functioning of the participants. When

students arrived at the laboratory they were taken into the testing room

and invited to sit in a comfortable recliner for the testing.

Tactile Sensitivity: Finger tactile sensitivity was measured by a

female experimenter. To ensure placement accuracy of repeated tests, a

water-soluble circular ink mark 1cm diameter was placed on the center of

the distal portion of the dominant index finger. The monofilament tip was

placed inside the circular ink mark. On the lips, the monofilament was

placed in the middle of the selected half of the lower lip.

Prior to testing, the participant was shown the monofilaments and

the experimenter demonstrated, by pressing the tip of the monofilament

against her own skin, that the monofilament was neither dangerous nor

66

painful. The participants were then asked to close their eyes and place

their hand palm up with the fingers in a relaxed, curled position. For each

trial the participant was cued to attend to their tactile sensations when the

experimenter said “okay.” The experimenter then said “one” and then

“two.” The duration and emphasis of each word was as uniform as

possible. On either the count of one or the count of two, the experimenter

pressed the tip of the monofilament against the participant’s skin until the

monofilament bent. The experimenter held the monofilament against the

participant’s skin for approximately 1.5 seconds. The participant then was

asked to indicate whether they felt the monofilament on the count of one

or the count of two. The participant was instructed to guess if they were

not sure when the monofilament was applied.

The tactile sensitivity exam was conducted in three stages. The

first stage was an instruction and practice stage. This stage was designed

to ensure that the participants fully understood the tactile exam

procedures, and had received a sufficient amount of practice at the tactile

exam to limit practice-related improvements. The participants completed

21 trials such that each monofilament (seven different monofilament sizes)

was applied, in random order, 3 times. After each trial, the subject

67

received feedback regarding their accuracy. The data collected in this

stage was not used for data analysis.

In the second and third stages, the participants did not receive

feedback, and the data collected in these trials were used for data

analysis. The second stage included 70 trials such that each

monofilament (seven different monofilament sizes) was applied, in semi-

random order, 10 times. Based on the participant’s performance in the

second stage, four to five monofilaments were selected for use in the third

stage of testing. Four monofilaments were selected if the participant

demonstrated a very steep performance curve (e.g., rapidly shifting from

chance levels (5/10 correct) on smaller monofilaments to perfect

performance (10/10 correct) on larger monofilaments). Five

monofilaments were selected if the participant demonstrated a flatter

performance curve (e.g., gradually shifting from chance levels on smaller

monofilaments to better performance on mid-sized monofilaments (7/10 or

8/10 correct) to perfect performance on the largest sized monofilaments).

The third stage included 80 to 100 trials such that each monofilament was

applied, in semi-random order, 20 times. Thus the final four or five

monofilaments selected were applied a total of 30 trials each across the

two data collection stages (latter two stages overall). This exam was

68

conducted such that stage one and two for the fingers was followed by

stage one and two for the lips, and stage three for the fingers was followed

by stage three for the lips. Between the second and third finger and lip

stages the participants filled out questionnaires.

Blood Pressure: Blood pressure was measured after the

participant had been seated at least 30 minutes to ensure that

measurements reflected resting blood pressure.

Debriefing: When the participant completed the experiment they

were given experiment credit toward their Introduction to Psychology

course requirement, debriefed regarding the purpose of the experiment,

and provided therapy referral information should they choose to seek

counseling for their sexual difficulties.


Sexual Functioning

3.2.1 Design

The outcome variable was sexual functioning (sexual desire,

orgasm), and the predictor variables were, within subject, tactile sensation

(finger sensation threshold, lip sensation threshold), and between subject,

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medication group (fluoxetine, control). This was a repeated measures

design. Data were collected at baseline, week 1, week 4, and week 8.

3.2.2 Participants

The fluoxetine group consisted of 12 pre-menopausal females

between the ages of 18 and 35, who meet criteria for a DSM-IV-TR mood

disorder (excluding all disorders including manic or hypomanic episodes),

and who had been prescribed fluoxetine but had not yet initiated drug

treatment. Of the 12 fluoxetine participants, five (38%) reported using oral

contraceptives. Fluoxetine participants were recruited through the

University of Texas Counseling Center. Students who visited one of the

resident psychiatrists, and who were eligible for fluoxetine treatment

(determined by the psychiatrist), were informed of the option to participate

in the study. They were informed that participants would receive two

months fluoxetine treatment, free of charge, and would be paid $50 for

completion of the study. To determine whether the participants met

inclusion and exclusion criteria, a Masters level clinical psychology student

conducted a telephone based interview.

The control group consisted of 13 pre-menopausal females

between the ages of 18 and 35, who meet criteria for a DSM-IV-TR mood

70

disorder (excluding all disorders including manic or hypomanic episodes),

but who choose not to use antidepressant treatment. Of the 13 control

subjects, eight (42%) reported using oral contraceptives. Control

participants were recruited through Introduction to Psychology classes at

the University of Texas at Austin. Students were invited to complete an

internet based prescreening to determined whether they were female, in a

sexually active relationship, and potentially experiencing a clinically

significant mood disorder (BDI > 10). To determine whether the

participants met inclusion and exclusion criteria, they were interviewed by

a Masters level clinical psychology student.

All participants were currently involved in a sexual relationship or

reported that they masturbate. Participants were excluded if they had

received antidepressant treatment within the past six months. Participants

also were excluded if, prior to drug initiation, they met DSM-IV-TR criteria

for Hypoactive Sexual Desire Disorder, FSAD, FOD, or any sexual pain

disorders. Sexual difficulties are often associated with major depression.

Participants were only excluded for sexual difficulties if these difficulties

were not better accounted for by depression (based on telephone

interviews with prospective participants). This is consistent with the DSM-

IV-TR exclusion criteria for sexual disorders.

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3.2.3 Medication

The medication used in this dissertation was fluoxetine (trade name

Prozac – donated by Eli Lilly, Inc.). Participants were prescribed doses of

fluoxetine according to their psychiatrist’s recommendation. Nonetheless,

all participants received a dosage of 20mg throughout the duration of the

study.

3.2.4 Materials

Materials for this experiment are described in the Materials section

of Study 1. All materials used for Study 1 were used at the baseline visit

of Study 2. At visits 2-4 (i.e., weeks 1, 4, and 8), participants completed

modified versions of several questionnaires that reflected the amount of

time elapsed between visits. The modified version of the OFQ (see

Appendix J) included questions regarding the percentage of time specific

activities resulted in orgasm over the past week, the modified version of

the SFI (see Appendix K) included questions regarding sexual functioning

over the past week, and the modified version of the Medical Information

Questionnaire (see Appendix I) included questions regarding the number

of alcoholic drinks consumed and the number of cigarettes smoked in the

past week.

72

3.2.5 Procedure

Participants who were eligible for the study, and provided written

consent, participated in 4 experimental sessions: baseline, 1 week, 4

weeks, and 8 weeks. The fluoxetine participants received medication

immediately following the baseline visit, while the control participants did

not receive medication throughout the duration of the study. The

procedure for the first pre-drug session was identical to that used in Study

1. The second three sessions were similar to the first session with the

exception that the modified versions of the questionnaires were

administered and the DSFI Experience sub-test was not administered. At

the end of the final visit, all participants were debriefed. Fluoxetine

participants received two months medication free of charge and were paid

$50.00 for completion of the study. Control participants received 3.5

hours of experiment credit toward their Introduction to Psychology

experiment requirement, and were paid $50 for completion of the study.

Participants who withdrew from the study prior to the final visit received

$20.

73

CHAPTER 4: STATISTICAL ANALYSES

4.1 Tactile Sensitivity Threshold

Raw scores for each monofilament size were converted to percent

correct scores such that 100% correct indicates full tactile sensation and

50% correct indicates no tactile sensation (chance levels of perception).

Perceptual sensitivity to different monofilament sizes were plotted by fitting

the data to a cumulative normal distribution. Specifically, the true

cumulative normal psychometric function of each subject was estimated

by employing the least-squares method to calculate the curve that best fit

the percent correct scores of the five monofilament sizes. Threshold was

defined as the interpolated monofilament size at which the subject was

84% correct because, theoretically, this is the point at which threshold

estimate variability is least (Green, 1990).

4.2 Study 1: The Role of Tactile sensitivity in Female Sexual Arousal


4.2.1 Analytic Strategy

To validate differences between groups, a series of independent t-

test were conducted between FSAD and control groups, FOD and control

74

groups, and FSAD and FOD groups. Multinomial logistic regression was

performed to examine the association between tactile sensitivity (finger

sensation threshold, lip sensation threshold) and sexual functioning group

(FSAD, FOD, and control groups), and whether any of the potential

covariates should be used in statistical analysis. Similarly, binary logistic

regression was used to compare the FSAD and control groups, and the

FOD and control groups. Hierarchical linear modeling was used to

evaluate the association between tactile sensitivity (finger sensation

threshold, lip sensation threshold) and severity of sexual dysfunction

(FSFI Lubrication Domain, FSFI Orgasm Domain), and whether any of the

potential covariates should be used in statistical analysis.

4.2.2 Specific Analyses

4.2.2a Analysis of Group Differences in Sexual Functioning

A series of independent t-tests were used to compare groups.

Groups (FSAD, FOD, control) were compared for differences in length of

relationship, sexual experience (DSFI Experience sub-test), FSFI Desire,

Arousal, Lubrication, Orgasm, Satisfaction, Pain, and Full Scale scores.

Sexual experience was examined to ensure that any differences found

between groups could not be accounted for by differences in sexual

75

functioning. Lubrication and orgasmic functioning were examined

between groups to ensure that the FSAD, FOD, and the normal

functioning group differed on these indexes. Because of the increased

likelihood of Type I errors when multiple statistical tests are performed, we

considered only mean differences of p < .002 (p < .05/27) statistically

significant.

4.2.2b Covariates

Factors thought to affect sexual functioning were assessed to use as

potential covariates in statistical analysis. These included physical

characteristics such as blood pressure (systolic and diastolic), pulse, cigarette

use, alcohol use, psychological factors such as depression, anxiety, and body

image, and sexual factors such as comfort, contentment, compatibility, and

satisfaction with sexual partner.

Covariates and finger and lip threshold were tested for

multicollinearity using logistic regression analysis to examine the variance

inflation factor (VIF). In logistic regression (see below), covariates are

considered multicollinear if they have a VIF score of greater than 2.5

(Allison, 1999). Covariates that demonstrated significant multicollinearity

were combined with other covariates in which they were highly correlated,

76

or, if combining highly correlated variables was not possible, dropped from

the analyses.

A series of multinomial logistic regressions were performed to

determine whether any of the potential covariates should be included for

statistical analysis. Diagnostic category was entered as the dependent

variable (control group, FSAD group, and FOD group), and each potential

covariate was entered as a covariate. Covariates that were significantly

associated with diagnostic category were included in later statistical

analysis, after being converted into tercile scores to account for potential

nonlinearity.

4.2.2c Analysis of Female Sexual Arousal Disorder, Female Orgasm

Disorder, and Tactile Sensitivity

Multinomial logistic regression was used to determine whether

tactile sensation threshold was associated with DSM-IV-TR diagnostic

category. Sexual functioning group (control group, FSAD group, FOD

group) was entered as the dependent variable, and finger threshold and

lip threshold were entered as independent variables, controlling for

significant covariates.

77

To compare the FSAD and control groups, hierarchical binary

logistic regression was performed entering sexual functioning (control,

FSAD) as the dependent variable, covariates in the first block, lip in the

second block, and finger threshold in the third block. To compare the

FOD and control groups, hierarchical binary logistic regression was

performed entering sexual functioning (control, FOD) as the dependent

variable, covariates in the first block, lip threshold in the second block, and

finger threshold in the third block.

4.2.2d Analysis of Severity of Sexual Dysfunction and Tactile

Sensitivity

The relationship between the severity of sexual dysfunction and

tactile sensation thresholds was evaluated using hierarchical linear

regression. The Lubrication Domain of the FSFI was used as a

quantitative measure of FSAD severity (dependent variable) and finger

and lip threshold were used as the independent variables. To examine the

relationship between severity of orgasm dysfunction and tactile sensation

the Orgasm Domain of the FSFI was used as a quantitative measure of

FOD severity (dependent variable) and finger and lip threshold were used

as the independent variables. Using the same procedure described

78

above, the covariates were re-examined to determine whether a

significant relationship existed between each covariate and the Lubrication

Domain of the FSFI, and between each covariate and the Orgasm Domain

of the FSFI.


Sexual Functioning

4.3.1 Data Selection

Participants were only included in statistical analysis if they

completed two of the four visits. Three participants in the fluoxetine group

withdrew after the first visit, in two cases indicating a schedule that

precluded continued participation, and in one case the participant was

discontinued due to equipment failure. One participant in the control

group withdrew after the first visit, indicating a busy schedule and

discomfort with the exam procedures. Two fluoxetine participants

completed two of four visits, in both instances indicating a schedule that

precluded continued participation. Three fluoxetine participants completed

three of four visits, in all instances because the participant was

discontinued from the study after her psychiatrist had changed her

79

prescription from fluoxetine to an alternative antidepressant medication (in

such instances, the participant was paid the full $50). Four control

participants completed three of four visits, in all instances indicating a

schedule that precluded attending the final visit. Seven fluoxetine

participants completed four of four visits and nine control participants

completed four of four visits.

4.3.2 Analytic Strategy

First, a series of independent t-tests were used to verify that the

fluoxetine and control groups did not differ at baseline. The groups were

compared on baseline depression (BDI), sexual experience (DSFI

Experience subtest), and sexual functioning (FSFI Domains: Desire,

Arousal, Lubrication, Orgasm, Satisfaction, Pain). Because of the

increased likelihood of Type I errors when multiple statistical tests are

performed, we considered only mean differences of p < .0055 (p < .05/9)

statistically significant. To examine changes in tactile sensation and

sexual functioning over time in the fluoxetine and control groups, and

whether tactile sensitivity mediated antidepressant induced sexual

dysfunction, hierarchical linear modeling Version 5 (HLM) was used (Bryk

80

& Raudenbush, 1992; Bryk, Raudenbush, & Congdon, 1996). HLM is

described below.

4.3.2b Hierarchical Linear Modeling

HLM is designed to investigate data with a nested structure. That

is, change processes are evaluated taking into account individual baseline

differences and individual differences in change processes. Data is

evaluated within individuals (Level 1) as well as between individuals (Level

2). For example, in this dissertation, changes over time in sexual

functioning were examined within individuals (Level 1), and the association

between medication group (fluoxetine, control) and these change

processes were examined between individuals (Level 2).

Specifically, at Level 1 a regression equation is computed for each

participant such that a slope coefficient (β, unstandardized) is computed

for each participant. These slope coefficients are considered to be a

sample drawn from a population of slope coefficients and thus can be

compared to a slope coefficient of zero using a t-test. In this dissertation,

slope coefficients reflect the degree and direction of change in sexual

functioning and/or tactile sensation over time. Also at Level 1, a chi-square

test can be used to determine whether individual slopes significantly vary.

81

At Level 2, a new regression equation is computed that represents the

degree of association between Level 1 slopes and variables that differ

across individuals (e.g., medication versus no medication). The Level 2

slope coefficient (γ, unstandardized) can then be tested against a slope

coefficient of zero using a t-test.

4.3.3 Specific Analyses

4.3.3a Fluoxetine-Induced Changes in Tactile Sensitivity

HLM was used to examine whether fluoxetine-use may have

accounted for changes in tactile sensation threshold over time. The

control and fluoxetine groups were compared on finger and lip thresholds

across the four study visits. If similar and significant changes in tactile

sensation were noted across both groups, this would suggest that practice

effects might account for these changes rather than the effects of

fluoxetine-use. If significant changes were noted for only the fluoxetine

group, this would suggest that fluoxetine, rather than practice effects might

account for these changes.

To evaluate fluoxetine-induced changes in finger threshold, finger

threshold was entered as the outcome variable, time was entered as a

Level 1 predictor variable, and group was entered as a Level 2 variable.

82

To evaluate fluoxetine-induced changes in lip threshold, lip threshold was

entered as the outcome variable, time was entered as a Level 1 predictor

variable, and group was entered as a Level 2 variable.

4.3.3b Manipulation Check: Analysis of Fluoxetine-Induced Sexual

Dysfunction

HLM was used (1) to perform a manipulation check to determine

whether the fluoxetine and controls groups differed over time in sexual

desire (FSFI Desire Domain), arousal (FSFI Lubrication Domain), and

orgasm (FSFI Orgasm Domain). For the manipulation check, sexual

functioning (sexual desire, arousal, orgasm) was entered as the outcome

variable, time (baseline, week 1, week 4, week 8) as the Level 1 predictor

variable, and medication group (fluoxetine, control) as the Level 2

predictor variable. Sexual desire, arousal, and orgasm were examined in

separate models.

4.3.3c Analysis of Tactile Sensation as a Mediator of Fluoxetine-

Induced Sexual Dysfunction

HLM was used to determine whether tactile sensation mediates

antidepressant-induced sexual dysfunction by examining the fluoxetine

83

and control groups in separate Level 1 models. Sexual desire, arousal,

and orgasm were entered as outcome variables, and time and tactile

sensation were entered as Level 1 predictor variables. Finger sensation

and lip sensation were entered in separate models. If tactile sensation

mediates antidepressant-induced changes in sexual functioning, it would

be expected that entering finger or lip sensation threshold into the models

would eliminate significant associations between sexual functioning and

time among the fluoxetine subjects. It is also possible that the control

participants may exhibit significant changes in sexual functioning across

time and that tactile sensation also mediates these changes. If so,

entering finger or lip sensation threshold into the control group models

would eliminate significant associations between sexual functioning and

time as well. This would suggest that individuals who exhibit changes in

sexual functioning, following medication-use or as a result of non-

medication factors, also exhibit changes in tactile sensation threshold.

4.3.3d Mediation Effect

Baron and Kenny (1986) provided several characteristics that a

variable must demonstrate in order to be considered a mediator. Firstly,

84

variations in the independent variable should account for variations in the

hypothesized mediator. Secondly, variations in the hypothesized mediator

should account for variations in the dependent variable. Thirdly, when the

relationship between the hypothesized mediator and the independent and

dependent variables are controlled, the association between the

independent and dependent variables is no longer statistically significant.

In the present dissertation, tactile sensation will be considered a mediator

of antidepressant-induced sexual functioning if (1) the association

between fluoxetine-use and tactile sensation is significant, (2) the

association between tactile sensation and sexual functioning is significant,

and (3) the association between fluoxetine-use and sexual functioning is

no longer statistically significant when tactile sensation is entered into the

model.

85

CHAPTER 5: RESULTS


Disorder and Female Orgasmic Disorder

5.1.1 Analysis of Group Differences in Sexual Functioning

The FSAD group did not significantly differ from the control group in

length of relationship (t(31) = .182, p > .05) or sexual experience (t(31) = -

.448, p > .05). In addition, they did not differ on the FSFI Desire Domain

(t(31) = -1.140, p > .05) or FSFI Satisfaction Domain (t(31) = -3.073, p =

.004). The groups significantly differed on the FSFI Arousal (t(31) = -

3.751, p = .001), Lubrication (t(31) = -6.554, p <.001), Orgasm (t(31) = -

3.548, p = .001), and Pain Domains (t(31) = -3.572, p = .001), and on the

Total Score (t(31) = -5.310, p < .001).

The FOD group did not significantly differ from the control group in

length of relationship (t(33) = -.542, p > .05), sexual experience (t(33) = -

1.822, p > .05), FSFI Desire (t(33) = -2.068, p = .047), Lubrication (t(33) =

-2.859, p = .007), or Pain Domain Scores (t(33) = -3.072, p = .004). The

groups significantly differed on the FSFI Arousal (t(33) = -3.844, p = .001),

86

Orgasm (t(33) = -13.945, p < .001), and Satisfaction Domains (t(33) = -

3.582, p = .001), and on the Total Score (t(33) = -6.401, p < .001).

The FSAD and FOD groups did not significantly differ in length of

relationship (t(30) = .851, p > .05) or sexual experience (t(30) = -1.167, p >

.05). In addition, they did not differ on the FSFI Desire (t(30) = .658, p >

.05), Arousal (t(30) = .908, p > .05), Lubrication (t(30) = -1.245, p > .05),

Satisfaction (t(30) = .106, p > .05), or Pain Domains (t(30) = .803, p > .05),

or on the Total Score (t(30) = 1.653 p > .05). The groups significantly

differed on the FSFI Orgasm Domain (t(30) = 6.737, p < .001). The

overlap between the FSAD and FOD women on the FSFI Arousal and

Lubrication Domains is consistent with previous studies noting that both

FSAD women (Rosen et al., 2000) and FOD women (Meston, 2003) report

significant problems with sexual arousal and lubrication compared to

normally functioning women. See Table 1.

5.1.2 Analysis of Tactile Sensation

The cumulative normal psychometric functions for finger and lips,

for the FSAD, FOD, and control groups, are provided in Figure 1 and

Figure 2, respectively. Threshold was defined as the milligrams of

applied force at which the participant was 84% correct, illustrated by the

87

horizontal line in Figure 1 and 2. Finger and lip threshold were

significantly correlated (r = .315, p = .031).

Table 1: Group Differences in Sexual Functioning___________________ Control FSAD FOD (n = 17) (n = 15) (n = 17) Measure mean (SD) mean (SD) mean (SD) __________________________________________________________ Length of Relationship (months) 13.7 (13.4) 14.5 (9.2) 11.5 (10.2) Sexual Experience 20.7 (1.9) 20.4 (2.2) 19.6 (1.7) FSFI Sexual Desire 8.2 (1.3) 7.5 (1.9) 7.1 (1.7) Arousal 18.2 (1.6) 15.3 (2.8)* 14.2 (4.2)* Lubrication 19.7 (0.8) 15.1 (2.9)* 16.7 (4.3) Orgasm 13.7 (1.4) 10.8 (3.1)* 4.1 (2.5)* Satisfaction 14.2 (1.2) 11.5 (3.4) 11.4 (3.0)* Pain 14.3 (0.9) 11.7 (3.0)* 10.4 (5.3) Total Score 33.2 (1.9) 26.9 (4.5)* 23.9 (5.8)* __________________________________________________________ Note: Sexual Experience scores were raw scores, on a 24 point scale (from the DSFI Experience sub-test). T-tests were conducted comparing control women to FSAD women, and control women to FOD women. * p < .002

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Figure 1: Tactile Sensitivity on the Index Finger

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Figure 2: Tactile Sensitivity on the Lips

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5.1.3 Analysis of Covariates

Systolic blood pressure (VIF = 3.364), diastolic blood pressure (VIF

= 3.090), BDI score (VIF = 2.859), and FSSS Compatibility scale (VIF =

3.045) all demonstrated multicollinearity. Systolic and diastolic blood

pressure were significantly correlated (r = .793, p < .01) and thus systolic

blood pressure was dropped from the analysis. BDI scores were

significantly correlated with several variables (cigarette use r = .460, p <

.01; BAI score r = .435, p < .01; body image r = -.640, p < .01; FSSS

Contentment scale r = -.318, p < .05; FSSS Communication scale r = -

.344, p < .05; FSSS Compatibility scale r = -.336, p < .05). Depression is

a factor that is highly likely to be associated with sexual problems and

since it would therefore be inappropriate to drop it from the model, BDI

and BAI scores (r = .435, p < .01) were combined to produce a single

mood score. The FSSS Compatibility scale was significantly correlated

with several variables (pulse r = -.316, p < .05; cigarette use r = -.281, p <

.05; BDI r = -.336, p < .05; BAI r = -.343, p < .05; Body Image r = .352, p <

.05; FSSS Contentment scale r = .722, p < .01; FSSS Communication

scale r = .618, p < .01). Sexual compatibility is a factor that is likely to be

significantly related to sexual functioning and thus it was combined with

the variable it was most highly correlated with, FSSS Contentment. Re-

90

examination of VIF using the above-described modifications indicated that

issues of multicollinearity were resolved.

Pulse (BFSAD = -.056, BFOD = .074, χ2 (2) = 9.838, p = .007) and

FSSS Contentment/Compatibility (BFSAD = -.296, BFOD = -.336, χ2 (2) =

10.784, p = .005) significantly predicted sexual functioning. Both pulse

and FSSS Contentment/Compatibility were converted to tercile scores in

order to account for possible nonlinearity. See Table 2.

Although cigarette smoking was not a significant predictor of sexual

functioning, two members of the FSAD group (per week cigarette use: 25

and 40) and one member of the FOD group smoked (per week cigarette

use: 100) more than a pack of cigarettes a week, while none of the control

participants identified themselves as significant smokers (the one control

participant who indicated that she smoked reported that she only smoked

one cigarette per week). Linear regression nonetheless indicated that

cigarette use was not significantly associated with either finger (B = .091,

SE = .089, t = 1.028, p = .309) or lip threshold (B = -.001, SE = .066, t = -

.017, p = .987). Cigarette use may not have been significantly associated

with either sexual functioning or tactile sensation in the present sample

due to the young age of the participants, and the fact that they may not

have been smoking sufficiently long enough to sustain damage to

91

Table 2: Summary of Covariates

Control FSAD FOD

Covariate Mean B

(SD) Mean (SD) Mean (SD) BFSAD FOD χ2 (2) p

Systolic BP 115.4 (15.5) 115.3 (13.6) 109.5 (13.4) .000 -.031 1.930 .381

Diastolic BP

73.5 (10.1) 74.0 (10.5) 71.8 (11.8) .005 -.015 .403 .817

Pulse 72.2 (8.2) 68.3 (8.6) 78.6 (10.7) -.056 .074 9.838 .007

Cigarette Use (per/wk) .1 (.5) 4.3 (11.8) 6.9 (24.1) .435 .443

4.714 .095

Alcohol Use (per/wk) 2.8 (3.0) 2.9 (3.4) 2.8 (2.8) .012 .000 .014 .993

Anxiety (BAI) 11.2 (7.3) 9.5 (6.1) 11.8 (5.3) -.048 .015 1.159 .560

Depression (BDI) 5.2 (3.8) 6.0 (5.9) 7.9 (8.7) .028 .071 1.680 .432

Body Image (DSFI) 3.8 (.6) 3.6 (.6) 3.5 (.8) -.413 -.711 1.787 .409

FSSS Contentment 23.7 (2.0) 20.5 (4.5) 18.7 (3.5) -.329 -.457 16.69 .000

FSSS Communicat. 27.8 (3.8) 25.5 (4.1) 25.6 (4.3) -.162 -.159 3.612 .164

FSSS Compatibility 27.8 (2.8) 24.5 (5.4) 25.0 (5.5) -.178 -.161 5.168 .075

92

mechanisms likely to affect sexual functioning and tactile sensation (e.g.,

vascular mechanisms).she smoked reported that she only smoked one

cigarette per week). Linear regression nonetheless indicated that

cigarette use was not significantly associated with either finger (B = .091,

SE = .089, t = 1.028, p = .309) or lip threshold (B = -.001, SE = .066, t = -

.017, p = .987). Cigarette use may not have been significantly associated

with either sexual functioning or tactile sensation in the present sample

due to the young age of the participants, and the fact that they may not

have been smoking sufficiently long enough to sustain damage to

mechanisms likely to affect sexual functioning and tactile sensation (e.g.,

vascular mechanisms).

5.1.4 Analysis of Tactile Sensitivity and Sexual Functioning

The likelihood ratio tests for finger threshold (BFSAD = .119, SE =

.061, Exp(B)FSAD = 1.126; BFOD = -.016, SE = .059, Exp(B)FOD = .985;

χ2(2) = 6.386, p = .041) indicated that finger threshold significantly

predicted the occurrence of DSM-IV-TR sexual dysfunction. The

likelihood ratio test for lip threshold (BFSAD = .068, SE = .076, Exp(B)FSAD =

1.070; BFOD = -.111, SE = .088, Exp(B)FOD = .895; χ2(2) = 3.986, p = .136)

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indicated that lip threshold did not significantly predict the occurrence of

DSM-IV-TR sexual dysfunction.

This multinomial logistic regression was repeated, entering finger

and lip threshold separately. When finger threshold, but not lip threshold,

was entered, the likelihood ratio test for finger threshold (BFSAD = .123, SE

= .057, Exp(B)FSAD = 1.131; BFOD = -.057, SE = .055, Exp(B)FOD = .945;

χ2(2) = 11.665, p = .003) significantly predicted the occurrence of DSM-IV-

TR sexual dysfunction. When lip threshold, but not finger threshold, was

entered, the likelihood ratio test for lip threshold (BFSAD = .086, SE = .062,

Exp(B)FSAD = 1.090; BFOD = -.131, SE = .084, Exp(B)FOD = .877; χ2(2) =

7.658, p = .022) significantly predicted the occurrence of DSM-IV-TR

sexual dysfunction. The difference in the likelihood ratio tests, when finger

and lip threshold were entered separately and together, indicates that

some of what is predicted by finger threshold is also predicted by lip

threshold.

The wald statistic test from the multinomial logistic regressions

suggested that tactile sensation threshold may differentially predict the

occurrence of FSAD versus FOD. To compare the FSAD and control

groups, planned hierarchical binary logistic regression was performed.

After pulse and FSSS Contentment/Compatibility were entered, the

94

likelihood ratio test indicated that the two variables (χ2(4) = 8.745, p =

.068) did not significantly predict the occurrence of FSAD versus control.

After lip threshold was entered, the likelihood ratio test indicated that the

block (B = .062, SE = .062, Exp(B) = 1.064, χ2(1) = 1.009, p = .315) did

not significantly predict the occurrence of FSAD. After finger threshold

was entered, the likelihood ratio test indicated that the block (B = .139, SE

= .074, Exp(B) = 1.149, χ2 (1) = 5.606, p = .018) significantly predicted the

occurrence of FSAD versus control. See Figures 3 and 4. In this sample,

71.4 % of FSAD participants would be correctly classified as FSAD, and

76.5 % of control participants would be correctly classified as control.

Thus, 28.6 % of participants would be false negatives, and 23.5 % would

be false positives.

Figure 3: FSAD vs. Control, Lip Threshold

Lip Threshold (mg)

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Figure 4: FSAD vs. Control, Finger Threshold

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Hierarchical binary logistic regression was performed to compare

the FOD and control groups. After pulse and FSSS

Contentment/Compatibility were entered, the likelihood ratio test indicated

that the two variables (χ2(4) = 8.543, p = .074) did not significantly predict

the occurrence of FOD versus control. After lip threshold was entered, the

likelihood ratio test indicated that the block (B = - .119, SE = .088, Exp(B)

= .888, χ2(1) = 2.334, p = .127) did not significantly predict the occurrence

of FOD versus control. After finger threshold was entered, the likelihood

ratio test indicated that the block (B = - .024, SE = .060, Exp(B) = .976,

χ2(1) = .166, p = .684) did not significantly predict the occurrence of FOD

versus control. See Figures 5 and 6. In this sample, 75 % of FOD

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participants would be correctly classified as FOD, and 76.5 % of control

participants would be correctly classified as control. Thus, 25 % of

participants would be false negatives, and 23.5 % would be false

positives.

Figure 5: FOD vs. Control, Lip Threshold

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Figure 6: FOD vs. Control, Finger Threshold


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Threshold

The relationship between the severity of sexual dysfunction and

tactile sensation thresholds was evaluated using hierarchical linear

regression. The covariates were re-examined to determine whether a

significant relationship existed between each covariate and the Lubrication

Domain of the FSFI. Linear regression was performed entering each

potential covariate as an independent variable, but only FSSS

Contentment (B = .564, t = 5.121, p < .001, R2 = .466) and FSSS

Compatibility (B = .334, t = 3.029, p = .005, R2 = .234) were significantly

associated with the FSFI Lubrication domain. The FSSS Contentment and

FSSS Compatibility domains were significantly correlated (r = .786, p <

.001) and thus were combined into a single FSSS

Contentment/Compatibility variable.

To examine the relationship between severity of arousal

dysfunction and tactile sensation, hierarchical linear regression was

performed by entering FSSS Contentment/Compatibility into the first

block, and lip threshold into the second block, and finger threshold into the

third block. FSSS Contentment/Compatibility was significantly associated

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with lubrication functioning (B = .491, SE = .116, t = 4.235, p < .001, R2 =

.382). Controlling for FSSS Contentment/Compatibility, lip threshold (B = -

.037, SE = .061, t = -.611, p = .546, R2 Change = .008) was not significantly

associated with lubrication functioning. Controlling for FSSS

Contentment/Compatibility and lip threshold, finger threshold (B = -.063,

SE = .047, t = -1.334, p = .190, R2 Change = .038) was not significantly

associated with lubrication functioning.

To determine whether any outliers in the data could be significantly

affecting the model, studentized residuals were computed. Studentized

residuals above 2.0 were considered as indicative of outliers. Two of the

FSAD subjects met these criteria and the model was re-examined after

these subjects were removed. FSSS Contentment/Compatibility was

significantly associated with lubrication functioning (B = .343, SE = .099, t

= 3.471, p = .002, R2 = .309). Controlling for FSSS

Contentment/Compatibility, lip threshold was not significantly associated

with lubrication functioning (B = -.011, SE = .049, t = -.232, p = .818, R2

Change = .001). Controlling for FSSS Contentment/Compatibility and lip

threshold, finger threshold was significantly associated with lubrication

functioning (B = -.089, SE = .035, t = -2.546, p = .017, R2 Change = .142).

See Figures 7 and 8.

99

Figure 7: Severity of Arousal Dysfunction

and Lip Threshold

Lip Threshold (mg)

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Figure 8: Severity of Arousal Dysfunction

and Finger Threshold


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The covariates were re-examined to determine whether a

significant relationship existed between each covariate and the Orgasm

Domain of the FSFI. Linear regression was performed entering each

100

potential covariate as an independent variable, but only pulse (B = -.193, t

= -2.163, p = .038, R2 = .128), FSSS Contentment (B = 1.032, t = 6.052, p

< .001, R2 = .534), and FSSS Compatibility (B = .455, t = 2.347, p = .025,

R2 = .147) were significantly associated with the Orgasm Domain of the

FSFI. Contentment and FSSS Compatibility were significantly correlated (r

= .691, p < .001) and thus were combined into a single FSSS

Contentment/Compatibility variable.

To examine the relationship between severity of orgasm

dysfunction and tactile sensation, hierarchical linear regression was

performed by entering pulse and FSSS Contentment/Compatibility into the

first block, lip threshold into the second block, and finger threshold into the

third block. FSSS Contentment/Compatibility (B = .769, SE = .258, t =

2.981, p = .006), but not pulse (B = -.024, SE = .097, t = -.249, p = .805),

was significantly associated with orgasm functioning (R2 = .326).

Controlling for pulse and FSSS Contentment/Compatibility, lip threshold

was not significantly associated with orgasm functioning (B = .183, SE =

.120, t = 1.532, p = .136, R2 Change = .050). Controlling for pulse, FSSS

Contentment/Compatibility, and lip threshold, finger threshold was not

significantly associated with orgasm functioning (B = .163, SE = .100, t =

1.631, p = .114, R2 Change = .054). Studentized residuals indicated one

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significant outlier. The model was re-examined after this subject was

removed but the association between finger and lip threshold remained

non-significant. See Figures 9 and 10.

Figure 9: Severity of Orgasm Dysfunction

and Lip Threshold

Lip Threshold (mg)

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Figure 10: Severity of Orgasm Dysfunction

and Finger Threshold


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5.1.6 Effect Sizes

Comparison between the FSAD and control groups indicated a

large effect size (Cohen’s d = .8657) while comparison between the FOD

and control groups indicated a small to medium effect size (Cohen’s d =

.3270)(Cohen, 1988).

5.2 Study 2: The Effect of Fluoxetine Treatment on Tactile Sensitivity

and Sexual Functioning

5.2.1 Analysis of Group Differences at Baseline

The groups did not differ on baseline BDI scores (t(23) = -.512, p =

.614), sexual experience (t(23) = .660, p = .516), FSFI Desire (t(23) =

.235, p = .817), FSFI Arousal (t(23) = -.684, p = .501), FSFI Lubrication

(t(23) = -.605, p = .551), FSFI Orgasm (t(23) = -1.279, p = .214), FSFI

Satisfaction (t(23) = .599, p = .555), FSFI Pain (t(23) = .370, p = .715), or

FSFI Full Scale Score (t(23) = -.307, p = .762). See Table 3.

5.2.2 Analysis of Changes over Time

The data were initially examined to determine whether change in

sexual functioning over time (sexual functioning as the outcome variable

103

Table 3: Sexual Functioning in Fluoxetine and Control Groups at Baseline

__________________________________________________________

Measure Control Fluoxetine (n = 13) (n = 12) mean (SD) mean (SD) p __________________________________________________________ Depression (BDI) 23.4 (8.5) 25.1 (8.0) >. 05 Sexual Experience 20.7 (2.8) 19.6 (5.3) >. 05 FSFI Sexual Desire 6.8 (2.4) 6.6 (2.3) >. 05 Arousal 13.2 (5.6) 14.6 (4.2) >. 05 Lubrication 14.9 (6.0) 16.1 (3.5) >. 05 Orgasm 8.6 (4.5) 10.8 (3.8) >. 05 Satisfaction 11.3 (2.8) 10.4 (4.8) >. 05 Pain 11.2 (4.7) 10.6 (4.3) >. 05 Total Score 25.0 (8.2) 25.8 (5.5) >. 05 __________________________________________________________

and time as the predictor variable) was best described as linear or

categorical. Change over time as a linear variable was defined as day 0,

day 7, day 30 and day 60, corresponding to the four study visits. Change

over time as categorical variables were entered as three dummy variables

such that week 1, 4, and 8 were compared to the baseline visit. For the

FSFI Desire domain, categorical time was significantly better than no

predictors (χ2 (2) = 43.172, p <.001) and linear (χ2 (2) = 44.782, p <.001).

For the FSFI Orgasm Domain, categorical time was significantly better

than no predictors (χ2 (2) = 28.102, p <.001) and linear (χ2 (2) = 33.609, p

104

<.001). Thus, for the present study, change over time was used in all

models as a categorical variable (dummy coded to reflect baseline, week

1, week 4, week 8). By using a categorical variable for time, the slope

coefficient represents change from baseline to visit 2, baseline to visit 3,

and baseline to visit 4, rather than change per unit of time.

5.2.3 Analysis of Fluoxetine-Induced Changes in Tactile Sensation

Finger sensation threshold significantly declined from baseline to

week 1 for the control group (β = -12.872, SE = 5.906, t = -2.179, p = .029)

and medication did not change the temporal pattern (γ = -17.593, SE =

18.492, t = -.951, p = .342). Finger sensation threshold did not

significantly change in the control group from baseline to week 4 (β = -

7.830, SE = 6.644, t = -1.178, p = .239) or week 8 (β = 15.382, SE =

19.884, t = .774, p = .447), and medication did not change the temporal

pattern (week 4: γ = -21.107, SE = 18.898, t = -1.117, p = .265)(week 8: γ

= -39.198, SE = 31.242, t = -1.255, p = .223). This indicates that practice

effects may account for significant improvements in finger sensation from

baseline to week one, rather than fluoxetine-induced changes. Analyses

indicating significant findings involving finger threshold, particularly

between baseline and week 1, must therefore be interpreted with caution.

105

See Figure 11. The psychometric functions for the baseline, week 1,

week 4, and week 8 visits are illustrated in Figure 12. This figure depicts

the finger psychometric functions for the medication group – the control

group had similar psychometric functions to the fluoxetine group, and thus

a separate figure is not provided.

Figure 11: Finger Threshold

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Figure 12: Tactile Sensitivity on the Index Finger for the Fluoxetine Group

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Lip sensation threshold did not significantly decline for the control

group from baseline to week 1 (β = -.134, SE = 2.705, t = -.050, p = .961)

and medication did not alter the temporal pattern (γ = .418, SE = 3.583, t =

.117, p = .908). Lip sensation threshold significantly declined for the

control group from baseline to week 4 (β = -4.860, SE = 2.137, t = -2.274,

p = .023) and medication tended to alter the temporal pattern (γ = 7.977,

SE = 4.274, t = 1.867, p = .062). Lip sensation threshold did not

significantly decline from baseline to week 8 (β = -17.114, SE = 10.817, t =

-1.582, p = .127) and medication did not alter the temporal pattern (γ =

19.614, SE = 11.875, t = 1.652, p = .112). This indicates that the control

group may have exhibited practice-related improvements between

baseline and week 4, while the fluoxetine group tended to show declines

in lip sensitivity. Analyses of lip threshold that indicate significant findings

at week 4 must nonetheless be interpreted with caution. See Figure 13.

The baseline, week 1, week 4, and week 8 psychometric functions for the

medication group are illustrated in Figure 14 – the control group had

similar psychometric functions to the fluoxetine group, and thus a separate

figure is not provided. The correlation between finger and lip sensation

was significant (r = .320, p = .003).

107

Figure 13: Lip Threshold

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Figure 14: Tactile Sensitivity on the Lips for the Fluoxetine Group

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5.2.4 Tactile Sensation as a Mediator of Antidepressant-Induced

Sexual Dysfunction

5.2.4a Sexual Desire

Manipulation check: The control group exhibited a significant decline in

sexual desire from baseline to week 1 (β = -1.333, SE = .627, t = -2.125, p

= .033), but no significant change from baseline to week 4 (β = -.453, SE =

.750, t = -.604, p = .551) or week 8 (β = 2.593, SE = 1.604, t = 1.617, p =

.119). Medication did not alter the temporal changes in sexual desire from

baseline to week 1 (γ = .853, SE = .808, t = 1.055, p = .292) or week 4 (γ

= -.726, SE = .991, t = -0.733, p = .471), but significantly altered temporal

changes in sexual desire from baseline to week 8 (γ = -4.088, SE = 1.877,

t = -2.178, p = .040). See Figure 15.

Figure 15: Changes in Sexual Desire

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Fluoxetine Group: Sexual desire did not significantly decline from baseline

to week 1 (β = -.519, SE = .558, t = -0.930, p = .359), significantly declined

from baseline to week 4 (β = -1.220, SE = .595, t = -2.050, p = .047), and

did not significantly decline from baseline to week 8 (β = -1.491, SE =

.953, t = -1.564, p = .146). When finger threshold was entered into the

model as a predictor variable, it did not alter the pattern of temporal

change in sexual desire; sexual desire tended to decline from baseline to

week 1 (β = -1.170, SE = .593, t = -1.971, p = .056), significantly declined

from baseline to week 4 (β = 1.803, SE = .621, t = -2.904, p = .007), and

tended to decline from baseline to week 8 (β = -1.938, SE = .893, t = -

2.169, p = .053). That is, finger threshold did not mediate antidepressant-

induced declines in sexual desire. Finger threshold had a significant

independent association with sexual desire (β = -.027, SE = .007, t = -

3.859, p = .003). The independent association between sexual desire

and finger threshold is illustrated below in Figure 16.

A similar analysis was performed to determine whether lip threshold

mediated antidepressant-induced sexual dysfunction. Adding lip threshold

into the model did not significantly alter the time slope, though it modestly

changed the significance of the slope variable; sexual

110

Figure 16: Independent Association:

FSFI Sexual Desire and Finger Threshold


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changed the significance of the slope variable; sexual desire did not

significantly decline from baseline to week 1 (β = -.373, SE = .520, t = -

0.717, p = .478), week 4 (β = -982, SE = .580, t = -1.692, p = .099), or

week 8 (β = -1.375, SE = 1.091, t = -1.261, p = .234). That is, lip threshold

did not mediate antidepressant-induced declines in sexual desire. Lip

threshold did not have a significant independent association with sexual

desire (β = -.070, SE = .044, t = -1.582, p = .142).

111

Control Group: Sexual desire was entered as the outcome variable and

time was entered as the predictor variable. Sexual desire tended to

decline from baseline to week 1 (β = -1.333, SE = .678, t = -1.967, p =

.056), but showed no significant change from baseline to week 4 (β = -

.496, SE = .691, t = -.717, p = .477), or week 8 (β = 2.625, SE = 1.586, t =

1.655, p = .123). When finger threshold was entered into the model as a

predictor variable, it strengthened the temporal change in sexual desire at

week 8; sexual desire did not significantly change from baseline to week 1

(β = -.882, SE = .641, t = -1.577, p = .122), or week 4 (β = .201, SE =

.680, t = .264, p = .793), but significantly increased from baseline to week

8 (β = 3.400, SE = 1.635, t = 2.216, p = .047). Finger threshold tended to

have an independent association with sexual desire (β = .036, SE = .023, t

= 1.973, p = .072).

A similar analysis was performed to determine whether lip

threshold mediated changes in sexual desire over time. When lip

threshold was entered into the model as a predictor variable, it

strengthened the temporal change in sexual desire from baseline to week

1; sexual desire significantly declined from baseline to week 1 (β= -1.369,

SE = .675, t = -2.026, p = .049), but did not significantly change from

baseline to week 4 (β = -.580, SE = .704, t = -0.825, p = .415), or week 8

112

(β = 2.694, SE = 1.536, t = 1.754, p = .104). Lip threshold did not have a

significant independent association with sexual desire among the non-

medicated participants (β = .0004, SE = .035, t = -.010, p = .992). See

Figures 17 and 18.

Figure 17: Changes in Sexual Desire, Finger

Threshold in Model

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Figure 18: Change in Sexual Desire, Lip Threshold in Model

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5.2.4b Sexual Arousal

Manipulation check: The control group did not exhibit a significant change

in lubrication from baseline to week 1 (β = -3.750, SE = 2.255, t = -1.663,

p = .096), week 4 (β = .017, SE = 2.608, t = .007, p = .995), or week 8 (β =

-.974, SE = 2.106, t = -.462, p = .643). Medication did not alter the

temporal changes from baseline to week 1 (γ = .973, SE = 2.613, t = .372,

p = .709), week 4 (γ = .274, SE = 2.773, t = .099, p = .922), or week 8 (γ

= -.3699, SE = 3.053, t = -.121, p = .904). See Figure 19.

Figure 19: Changes in Lubrication

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Fluoxetine Group: Lubrication significantly declined from baseline to week

1 (β = -2.796, SE = 1.372, t = -2.038, p = .049), but did not significantly

change from baseline to week 4 (β = .274, SE = 1.463, t = .187, p = .853),

or week 8 (β = -1.442, SE = 1.658, t = -.869, p = .391). When finger

114

threshold was entered into the model as a predictor variable, it did not

alter the pattern of temporal change in lubrication; lubrication tended to

decline from baseline to week 1 (β = -2.784, SE = 1.322, t = -2.106, p =

.042), but did not significantly change from baseline to week 4 (β = .3997,

SE = 1.385, t = .289, p = .775) or week 8 (β = -.584, SE = 1.537, t = -.380,

p = .706). That is, finger threshold did not mediate antidepressant-

induced declines in lubrication. Finger threshold had a significant

independent association with lubrication (β = -.076, SE = .021, t = -3.676,

p = .004). The independent association between lubrication and finger

threshold is illustrated below, Figure 20.

Figure 20: Independent Association

FSFI Lubrication and Finger Threshold


300250200150100500

FSFI

Lub

ricat

ion

Dom

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22

20

18

16

14

12

10

8

6

4

20



115


changed the significance of the slope variable; lubrication did not

significantly decline from baseline to week 1 (β = -1.990, SE = 1.213, t = -

1.641, p = .106), week 4 (β = 1.223, SE = 1.347, t = .908, p = .371), or

week 8 (β = -.014, SE = 1.543, t = -.009, p = .993). That is, lip threshold

did not mediate antidepressant-induced declines in lubrication. Lip

threshold did not have a significant independent association with

lubrication (β = .025, SE = .088, t = .286, p = .780).

Control Group: Lubrication was entered as the outcome variable and time

was entered as the predictor variable. Lubrication did not significantly

change from baseline to week 1 (β = -3.750, SE = 2.807, t = -1.336, p =

.189), week 4 (β = .1798, SE = 2.813, t = .064, p = .950), or week 8 (β = -

.937, SE = 3.042, t = -.308, p = .760). Adding finger threshold into the

model did not alter the temporal pattern from baseline to week 1 (β = -

3.768, SE = 2.842, t = -1.326, p = .193), week 4 (β = .104, SE = 2.847, t =

.037, p = .971), or week 8 (β = -.826, SE = 3.073, t = -.269, p = .789).

Finger threshold did not have an independent association with lubrication

(β = -.0006, SE = .021, t = .030, p = .977).

A similar analysis was performed to determine whether lip

threshold mediated changes in lubrication over time. Adding lip threshold

116

into the model did not alter the temporal pattern from baseline to week 1

(β= -3.739, SE = 2.803, t = -1.334, p = .190), week 4 (β = -.482, SE =

2.854, t = -.169, p = .867), or week 8 (β = -1.783, SE = 3.099, t = -.575, p

= .568). Lip threshold did not have a significant independent association

with lubrication among the non-medicated participants (β = .050, SE =

.040, t = -1.238, p = .240). See Figures 21 and 22.

Figure 21: Changes in Lubrication, Finger Threshold in Model

02468

101214161820


FSFI

Lub

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ControlFluoxetine

Figure 22: Changes in Lubrication, Lip Threshold in Model

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FSFI

Lub

ricat

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Dom

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ControlFluoxetine

117

5.2.4c Orgasm

Manipulation Check: The control group did not exhibit any significant

changes in orgasm functioning from baseline to week 1 (β = -1.821, SE =

1.323, t = -1.376, p = .182), baseline to week 4 (β = .318, SE = 1.514, t =

.210, p = .836), or baseline to week 8 (β = 1.460, SE = 1.321, t = 1.105, p

= .270). Medication did not alter the temporal changes in orgasm from

baseline to week 1 (γ = .09, SE = 1.895, t = 0.047, p = .963), tended to

alter temporal changes in orgasm from baseline to week 4 (γ = -3.88, SE

= 2.223, t = -1.744, p = .094), and significantly altered temporal changes

in orgasm functioning from baseline to week 8 (γ = -4.18, SE = 1.992, t = -

2.097, p = .036). See Figure 23.

Figure 23: Changes in Orgasm

0.002.004.006.008.00

10.0012.0014.0016.00


FSFI

Org

asm

Dom

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ControlFluoxetine

118

Fluoxetine Group: Orgasm was entered as the outcome variable and time

was entered as the predictor variable. Orgasm tended to decline from

baseline to week 1 (β = -1.732, SE = .997, t = -1.737, p = .090), and

significantly declined from baseline to week 4 (β = -3.407, SE = 1.066, t = -

3.197, p = .003) and week 8 (β = -2.793, SE = 1.211, t = -2.307, p = .027).

Adding finger threshold into the model strengthened the temporal change

in orgasm from baseline to week 1, but did not alter the temporal change

in sexual desire from baseline to week 4 or week 8; orgasm ability

significantly declined from baseline to week 1 (β = -2.588, SE = .965, t = -

2.683, p = .011), week 4 (β = -4.013, SE = 1.027, t = -3.910, p = .001),

and week 8 (β = -2.555, SE = 1.143, t = -2.235, p = .032). That is, finger

threshold did not mediate antidepressant-induced declines in orgasmic

ability. Finger threshold tended to have an independent association with

orgasm (β= -.097, SE = .045, t = -2.168, p = .053).


mediated antidepressant-induced declines in orgasmic ability. When lip

threshold was entered into the model as a predictor variable, it did not

alter the temporal change in orgasm ability; orgasm ability tended to

decline from baseline to week 1 (β = -1.742, SE = 1.014, t = -1.717, p =

.094), and significantly declined from baseline to week 4 (β = -2.787, SE =

119

1.101, t = -3.075, p = .005) and to week 8 (β = -2.787, SE = 1.243, t = -

2.243, p = .031). That is, lip threshold did not mediate antidepressant-

induced declines in orgasmic ability. Lip threshold did not have a

significant independent association with orgasm ability (β = -0.11, SE =

.062, t = -0.176, p = .864).

Control Group: Orgasm was entered as the outcome variable and time

was entered as the predictor variable. Orgasm did not significantly

change at week 1 (β = -1.750, SE = 1.514, t = -1.156, p = .255), week 4 (β

= .492, SE = 2.041, t = .241, p = .813), or week 8 (β = 1.284, SE = 1.669, t

= .769, p = .446). When finger threshold was entered into the model as a

predictor variable, it did not alter the pattern of temporal change in orgasm

ability; orgasm ability did not significantly change at week 1 (β = -1.729,

SE = 1.444, t = -1.198, p = .238), week 4 (β = .161, SE = 2.034, t = .079, p

= .939), or week 8 (β = 1.599, SE = 1.622, t = .986, p = .331). Finger

threshold did not have a significant independent association with orgasm

(β = .017, SE = .014, t = 1.191, p = .257).


mediated changes in orgasmic ability over time. When lip threshold was

entered into the model as a predictor variable, it did not alter the pattern of

temporal change in orgasm ability; orgasm did not significantly change at

120

week 1 (β = -1.598, SE = 1.404, t = -1.138, p = .262), week 4 (β = 1.378,

SE = 1.994, t = .691, p = .502), or week 8 (β = 2.292, SE = 1.603, t =

1.430, p = .160). Lip threshold tended have an independent association

with orgasm (β = .052, SE = .028, t = 1.868, p = .086). See Figures 24

and 25.

Figure 24: Change in Orgasm, Finger Threshold in Model

0.002.004.006.008.00

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FSFI

Org

asm

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Figure 25: Changes in Orgasm, Lip Threshold in Model

0.002.004.006.008.00

10.0012.0014.0016.00


FSFI

Org

asm

Dom

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ControlFluoxetine

121

CHAPTER 6: DISCUSSION



6.1.1 Summary of the Main Findings

To my knowledge, this is the first study to examine tactile sensitivity

in women with FSAD and FOD, compared to normally functioning women.

Finger and lip threshold were significantly associated with FSAD versus

normal functioning women. Severity of arousal dysfunction was

associated with finger threshold but not lip threshold. That is, greater

impairment in sexual arousal functioning was associated with greater

impairment in finger sensation. Finger and lip threshold were not

significantly associated with FOD versus normal functioning women, and

severity of FOD was not associated with either finger or lip threshold.

6.1.2 Female Sexual Arousal Disorder, Normally Functioning

Women, and Tactile Sensitivity

Finger and lip sensation thresholds were significantly associated

with presence or absence of FSAD, and finger sensation threshold was

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significantly associated with severity of FSAD. These findings are

consistent with a pilot study among college-aged women who reported

vaginal dryness as little as twenty-five percent of the time, where the

authors noted significantly decreased tactile sensitivity on the finger as

compared to normally functionally college-aged women (Frohlich &

Meston, 1999).

Tactile sensitivity may be associated with FSAD because of

individual differences in tactile sensation mechanisms. Vaginal lubrication,

like erection, is a reflexive response (Sipski, 1991) and it is possible that

this reflex is impaired in women with sexual arousal problems, with the

impairment occurring at any point along the reflex arc. For example, it is

possible that women with arousal problems simply have fewer tactile

receptors than women without arousal problems. This hypothesis is

supported by evidence that the number and distribution of genital tactile

receptors varies and as women age, the number of genital tactile

receptors decreases (Krantz, 1958). In addition, women with complete

upper motor neuron spinal cord injuries are able to attain vaginal

lubrication with manual stimulation alone (Sipski et al., 1995b), which

suggests that vaginal lubrication requires intact and functional genital

tactile receptors but not conscious perception of tactile stimulation.

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Alternatively, the central nervous system processing of tactile

receptor signals may differ between women with and without FSAD.

Absolute threshold, or the amount of stimulation that produces afferent

unit impulses, does not vary within a specific receptor type across different

skin regions while the psychological threshold, or the amount of

stimulation needed for conscious perception of tactile stimulation, does

vary across skin regions. Absolute threshold and psychological threshold

are rarely similar except for a few regions that may have greater "tactile

significance." In other words, the central nervous system does not equally

weight tactile information received from different regions of the body

(Johansson & Vallbo, 1979a). It is possible that central nervous system

interpretation of tactile information differs between women with and

without sexual arousal problems.

The testing paradigm employed in this dissertation is likely to reflect

tactile sensitivity of only one type of receptor, the rapidly adapting receptor

(Johansson et al., 1980). Rapidly adapting receptors, in genital tissue, are

located in the mons verneris, labia majora, labia minora, and the clitoris

(Krantz, 1958). They vary in number and size depending upon several

factors such as age and development of the individual and the body

location. Genital tissue contains a wide variety of tactile receptors, in

124

addition to rapidly adapting receptors, however (Krantz, 1958), and

stimulation to all these receptors is likely to contribute to sexual arousal.

It is possible that women with FSAD differ in tactile sensation in one

receptor type but not another.

Given that previous studies have consistently found that men with

erectile dysfunction have reduced tactile sensation, it is not surprising that

the female analog of erectile dysfunction, FSAD, would also be associated

with reduced tactile sensation. It is possible that since erectile functioning

and vaginal lubrication are both dependent upon adequate blood flow to

the genital tissue, decreased tactile sensitivity found in these groups may

be related to abnormalities in vascular mechanisms. It is of note that

when genital tissue becomes engorged with blood, such as with erection,

tactile sensation is decreased and this decrease is more substantial in

men with erectile problems (Rowland, 1998). This suggests that

vasocongestion may differentially affect tactile mechanisms in individuals

with and without sexual arousal problems.

It is important to note that severity of arousal functioning was

significantly associated with finger threshold, but only after two outliers

were removed from the model. The two outliers were women with FSAD

who indicated fairly severe problems with vaginal dryness, but who also

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exhibited tactile sensation thresholds similar to women in the normally

functioning group. In addition, discriminant analysis indicated that just

under half (46.7%) of the FSAD women were incorrectly classified as

control participants using finger and lip threshold as predictor variables.

This suggests that tactile sensation is associated with FSAD for some

women but not others. This is consistent with a recently proposed model

of FSAD suggesting that the broad diagnostic category of FSAD may in

fact be comprised of several subtypes of FSAD (Basson, 2002). That is,

women with FSAD may have one of the following forms of FSAD: (1)

generalized FSAD characterized by lack of genital sensations (e.g.,

pulsing and throbbing), vasocongestion, and subjective pleasure; (2)

genital FSAD characterized by lack of genital response with the presence

of subjective excitement and arousal; (3) missed arousal characterized by

an inability to recognized genital responses; (4) dysphoric FSAD

characterized by a unpleasant or negative interpretation of genital arousal;

and (5) anhedonic FSAD characterized by a genital sensations and

vasocongestion without subjective pleasure (Basson, 2002). It is possible

that women with FSAD and impaired tactile sensation tend to have some

forms of FSAD but not others.

126

It is unclear why tactile sensation of the index finger but not the

lower lip was associated with severity of arousal functioning. It is possible

that lip sensation is associated with severity of arousal functioning but was

not detected in this dissertation. Alternative measures of cutaneous

sensation, such as vibrotactile sensation, temperature sensation, pain

sensation, or sensory nerve conduction velocity, may be more sensitive at

detecting individual differences in lip sensation. It is also possible that

problems with tactile sensation are more readily detected on areas of the

body that are more distal to the CNS. That is, declines in skin sensation

may be more readily noted on the more distal portions of the body (i.e.,

the extremities), than on the more proximal portions of the body. This

pattern has been noted in diabetic patients experiencing deterioration of

the peripheral nerves. Diabetic patients typically first exhibit loss of

sensation on the foot, and as the condition worsens, loss of sensation on

parts of the body more proximal to the CNS (Cavanagh, Simoneau,

Ulbrecht, 1993). It is possible that a similar albeit less pathological

process accounts for the significant findings noted for the fingers (more

distal) but not for the lips (more proximal) in this dissertation.

Lip sensation may not have distinguished between sexually

functional and dysfunctional women due to greater variation in lip

127

sensation across the menstrual cycle. The facial tissue contains a higher

density of estrogen receptors than the fingers (Hasselquist, Goldberg, &

Schreter, 1980), and animal and human studies suggest that exogenous

and endogenous estrogen levels affect tactile sensitivity. Female rats

treated with estrogen had larger facial trigeminal nerve receptive fields

(Bereiter & Barker, 1980), and larger pudendal receptive fields

(Komisaruk, Adler, & Hutchison, 1972), and rats and canaries exposed to

estrogen treatment displayed increased tactile sensitivity compared to

non-treated animals (Bereiter & Barker, 1980). Female rats were most

sensitive to pain (tailflick latency) during the proestrus phase of the

estrous cycle, a period when estradiol levels are high, and least sensitive

to pain during metestrus, when estradiol levels are decreased (Frye, Bock,

& Kanarek, 1992). To my knowledge, only one study has examined

hormonal fluctuations and skin sensation in humans and this study used

fairly crude methods for pinpointing hormone levels. Two-point

discrimination was evaluated on the lower forearm and tactile sensitivity

was evaluated on the middle finger in five normally cycling women prior to

the menstrual period (when estradiol levels are likely to be declining), and

after the menstrual period (when estradiol levels are likely to be low). The

women had better two-point discrimination and greater tactile sensitivity in

128

the pre-menstrual period compared to the post-menstrual period (Herren,

1933). To my knowledge, no studies have examined the effect of oral

contraceptive use on tactile sensation. In the present dissertation,

approximately half of the participants in each group reported oral

contraceptive use, suggesting that if oral contraceptive use affects tactile

sensation, it would have affected all three groups equally. Nonetheless,

since the lips have greater density of estrogen receptors than the fingers,

the lips may have been more affected by such menstrual cycle fluctuations

in estrogen than the fingers.

The fact that FSAD was significantly associated with an area of the

body, finger threshold, which is not a primary erogenous zone, is of

interest. This suggests that the underlying mechanism may be systemic

(albeit more markedly expressed on some parts of the body than others) –

perhaps a systemic abnormality in cutaneous sensation or a systemic

abnormality in a system that affects cutaneous sensation (such as

vascular mechanisms). This is consistent with studies in men that have

noted differences in tactile sensation on the penis and the fingers, with a

more marked group difference on the fingers than the penis (Morrissette et

al., 1999). In order to test this hypothesis, cutaneous sensation would

need to be measured on several different erogenous and non-erogenous

129

areas of the body. It is also possible that the abnormality in cutaneous

sensation is specific to the fingers. This possibility is most consistent with

the hypothesis that the group differences noted in this dissertation may

reflect differences in central nervous system processing of sensory

information. In other words, it is possible that when the system is

functioning normally, digital cutaneous stimulation and sexual stimulation

may be given greater tactile significance by the central nervous system

than other types of stimulation. If so, FSAD and reduced digital tactile

sensitivity may reflect a disregulation/abnormalities in this process.

6.1.3 Female Orgasm Disorder, Normally Functioning Women, and

Tactile Sensitivity

Neither finger nor lip thresholds were significantly associated with

FOD versus normally functioning women, or severity of orgasmic

functioning. It is important to note that the FOD women in this dissertation

differed somewhat from many clinically diagnosed FOD women in that

they did not report clinically significant arousal dysfunction. That is,

previous research suggests that approximately half of women diagnosed

with FOD are also diagnosed with FSAD (Meston, 2003). The FOD

women in this dissertation reported decreased subjective sexual arousal

130

(as measured by the FSFI Arousal domain score) compared to the control

women, but not decreased physiological sexual arousal (as measured by

the FSFI Lubrication domain score). It is possible that women with a dual

diagnosis of FOD and FSAD may have impaired tactile sensation, while

women with FOD alone may not. If so, this would suggest that FOD alone

versus a dual diagnosis of FOD and FSAD may be characterized by a

different etiology. In this dissertation, three women were identified who

had a dual diagnosis of FOD and FSAD (they were not included in

statistical analyses, see section 3.1.2b), and two of the three had finger

thresholds similar to FSAD women rather than FOD or control women.

It also is important to note that this dissertation examined only

women experiencing life-long, generalized anorgasmia, also known as

primary anorgasmia. It is possible that finger and lip threshold may be

associated with secondary anorgasmia. Women with secondary

anorgasmia report having difficulty reaching orgasm, and are only able to

reach orgasm in some situations (e.g., masturbation only), or with specific

types of stimulation (e.g., oral sex). It is possible that secondary

anorgasmia is associated with variations in tactile sensation, while primary

anorgasmia is not. In support of this hypothesis, evidence suggests that

secondary anorgasmia is much more difficult to treat with cognitive

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behavioral therapies than primary anorgasmia. Primary anorgasmia can

be successfully treated with education alone (particularly with highly

motivated patients), while this is not typically the case with secondary

anorgasmia (Heiman, 2000). In addition, empirically validated treatments

such as sensate focus and directed masturbation have shown high

success rates and long-term gains with primary anorgasmic patients, but

not secondary anorgasmic patients (Heiman & Meston, 1998). While

highly speculative, secondary anorgasmia may have a physiological

cause, while primary anorgasmia may not.

The findings from Study 1 are consistent with a study noting that

vibrotactile sensation on the glans penis was not associated with

premature ejaculation in men (Rowland et al., 1993). This finding,

however, is inconsistent with another study in men noting an association

between vibrotactile sensation and premature ejaculation (Xin et al.,

1996). The Xin et al. (1996) study was methodologically superior,

however, as Xin et al. (1996) examined vibrotactile sensation on several

areas of the body (index finger, glans penis, penile shaft, and scrotum -

found significant differences on the glans penis and penile shaft), and had

a significantly larger sample size (186 participants for Xin et al. (1996)

versus 63 participants for Rowland et al.(1993)). Taken together, this

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suggests that an association between FOD and cutaneous sensation may

be detected on the genital tissue using measures of vibrotactile sensation.

That is, it is possible that female genital vibrotactile sensation is

associated with FOD, while finger and lip punctate sensation is not.

Nonetheless, physiological and psychological sexual processes may not

be analogous between men and women, and thus such inferences must

be considered with caution.

It is possible that a significant association was found between finger

threshold and FSAD, but not finger threshold and FOD, due to the relative

importance of different parts of the body to arousal and orgasm

functioning. In women, sexual arousal may require stimulation to both

genital and non-genital areas of the body such that impairment in genital

and non-genital tactile mechanisms (such as the fingers), may disrupt

normal sexual arousal functioning. In contrast, most women require direct

clitoral and/or genital stimulation to reach orgasm (Heiman, 2000), and

thus genital tactile mechanisms may be critical to orgasm functioning,

while non-genital tactile mechanisms (such as the fingers) may not be. In

short, it is possible that FSAD is associated with impairment in systemic

sensation mechanisms, while FOD is associated with impairment in local,

genital sensation mechanisms.

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Sexual Functioning

6.2.1 Summary of the Main Findings

To my knowledge, this is the first study to examine tactile sensitivity

and sexual functioning in depressed women receiving fluoxetine

treatment, and a comparison group of depressed women who were

antidepressant-medication free. Consistent with previous studies, the

fluoxetine group, but not the control group, exhibited declines in orgasm

functioning, the groups exhibited significantly different changes in sexual

desire, while both groups did not exhibit significant changes in sexual

arousal functioning. Analyses suggest that tactile sensation does not

mediate antidepressant-induced sexual dysfunction and does not mediate

changes in sexual functioning over time among clinically depressed

women. Specifically, for the fluoxetine and control groups, changes in

sexual desire and changes in orgasmic functioning noted with

antidepressants could not be accounted for by either finger or lip

threshold. Consistent with previous findings, an independent association

between finger sensation threshold and arousal functioning was noted in

the fluoxetine group. In addition, a novel finding was that finger sensation

134

threshold had an independent association with sexual desire in the

fluoxetine group.

6.2.2 The Effect of Fluoxetine on Tactile Sensation

The data from this dissertation did not support the hypothesis that

fluoxetine produces changes in tactile sensation. When changes in finger

and lip sensation were observed, they did not significantly differ from

those seen in the control group, indicating that any changes noted are

likely to be attributed to practice effects. To our knowledge, only one other

study has examined fluoxetine-induced changes in cutaneous sensation,

and this study measured vibrotactile sensation in men, rather than

punctate sensation (Yilmaz et al., 1999). If fluoxetine produces changes

in tactile sensation among women, it is possible that it produces changes

in vibrotactile sensation, but not punctate sensation.

6.2.3 Experimental Manipulation: Fluoxetine-Induced Sexual

Dysfunction

Previous studies indicate that the most common sexual side effects

of SSRI medications in both men and women are decreased sexual

desire, delayed orgasm, and anorgasmia (Feiger et al., 1996; Meston &

135

Gorzalka, 1992; Montejo-Gonzalez et al., 1997; Patterson, 1993;

Pearlstein & Stone, 1994; Preskorn, 1995). In order to test the

hypotheses of this dissertation, that tactile sensation mediates fluoxetine-

induced sexual dysfunction, it was critical that the participants receiving

fluoxetine treatment experience to some extent the expected sexual side

effects noted with fluoxetine treatment. The manipulation was successful

with regard to orgasm functioning; the control group did not exhibit

significant changes in orgasmic functioning, while the fluoxetine group

experienced significant declines in orgasmic functioning following eight

weeks of fluoxetine treatment. The control group exhibited significant

improvements in sexual desire, while the fluoxetine group did not exhibit

significant changes in sexual desire. No changes in arousal functioning

were noted in either the control or fluoxetine groups. This finding was not

surprising, however, as arousal dysfunction is not among the more

commonly reported fluoxetine-induced sexual side effects (Feiger et al.,

1996; Meston & Gorzalka, 1992; Montejo-Gonzalez et al., 1997;

Patterson, 1993; Pearlstein & Stone, 1994; Preskorn, 1995).

136

6.2.4 Tactile Sensation as a Mediator of Fluoxetine-Induced Sexual

Dysfunction

Neither finger nor lip threshold mediated fluoxetine-induced sexual

desire or orgasm changes in this dissertation. Indeed, trends were in the

opposite direction. Significant findings and trends indicated that tactile

sensation strengthened the association between fluoxetine and temporal

changes in sexual functioning; strongly suggesting that tactile sensation

does not mediate fluoxetine-induced sexual side effects.

These findings suggest that if tactile sensation mediates fluoxetine-

induced sexual dysfunction, the changes in tactile sensation are not

systemic (i.e., affecting all regions of the body), and do not involve

punctate sensation. That is, it is possible that genital measures of

vibrotactile sensation, temperature sensation, or pain sensation mediate

antidepressant-induced sexual side effects while finger and lip punctate

sensation does not.

It is possible that tactile sensation may mediate antidepressant-

induced changes in sexual functioning among older populations of women.

The participants in the present sample were college-aged (ranged in age

from 18 to 32), which is younger than the age of the typical patient

presenting with clinically significant depression (Olfson, Zarin, Mittman, &

137

McIntyre, 2001). It is possible that fluoxetine has relatively little effect on

skin sensation among younger populations, but has a more profound

effect on older populations. If so, one would expect younger populations

taking antidepressant treatment to have fewer complaints of sexual side

effects than older populations. To my knowledge, age has not been

shown to be a significant predictive factor in the likelihood of experiencing

sexual side effects from antidepressant medication.

It is also possible that tactile sensation may mediate

antidepressant-induced changes in sexual functioning, but not among

depressed women. To my knowledge, only one other study has been

published examining the role of skin sensation in fluoxetine-induced

changes in sexual functioning. This study was a placebo-controlled trial of

fluoxetine as a treatment for premature ejaculation (Yilmaz et al., 1999).

The fluoxetine group, but not the control group, exhibited a significant

increase in penile sensory threshold and intravaginal latency following one

month of medication treatment. This suggests that fluoxetine may

produce changes in skin sensation and sexual functioning among sexually

dysfunction patients, but not among depressed patients.

138

6.2.5 Independent Association between Tactile Sensation and

Sexual Dysfunction

Consistent with a previous study (Frohlich & Meston, 1999) and

Study 1 of this dissertation, an independent association was found

between finger tactile sensation and arousal functioning. That is, in the

fluoxetine group, as arousal functioning decreased finger thresholds

increased - women reporting greater arousal problems exhibited less

sensitive skin on their fingers. This indicates that the association between

finger tactile sensation and arousal dysfunction is present among women

with FSAD, as well as among clinically depressed women receiving

fluoxetine. No significant independent associations were found between

lip sensation and arousal functioning in the fluoxetine group, and between

finger or lip sensation and arousal functioning in the control group.

A novel finding was that among the fluoxetine participants, finger

threshold had a significant independent association with sexual desire,

such that as sexual desire decreased, finger threshold increased. Among

the control participants, finger threshold tended to have an independent

association with sexual desire. In addition, among the fluoxetine

participants, finger threshold tended to have an independent association

with orgasm functioning, and among the control participants, lip threshold

139

tended to have an independent association with orgasm functioning. It is

possible that some of the noted trends reflect significant associations

between tactile sensation and sexual functioning that were not detected

due to the small sample used in this dissertation.

It is unclear why finger threshold may be associated with sexual

desire among patients receiving fluoxetine treatment. In this dissertation,

finger threshold did not mediate fluoxetine-induced changes in sexual

desire. This suggests that the association between finger threshold and

sexual desire cannot be explained by the same mechanism that produces

fluoxetine-induced changes in sexual desire. It is possible that the

association between tactile sensation and sexual desire is accounted for

by the association between tactile sensation and sexual arousal. That is,

it is possible that the women who experienced declines in sexual desire

are also the same women who experienced declines in sexual arousal and

that it is the sexual arousal changes, not the sexual desire changes, which

are associated with tactile sensation. Reexamination of the present data

indicated that changes in sexual arousal do not account for the

association between sexual desire and finger tactile sensation thresholds

(without FSFI Lubrication domain in the model, the independent

association between sexual desire and finger threshold: β = -.027, t = -

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3.859, p = .003; with FSFI Lubrication domain in the model, the

independent association between sexual desire and finger threshold

remained significant: β = -.020, t = -2.467, p = .031), despite a strong

independent association between FSFI Desire and FSFI Lubrication

domain scores (β = .223, t = 3.928, p = .001).

The independent association between sexual desire and finger

sensation thresholds, and sexual arousal and finger sensation thresholds,

suggests that the underlying mechanism may involve central nervous

system (CNS) processes. That is, the association between tactile

sensation and sexual dysfunction hypothetically could involve peripheral

tactile mechanisms (e.g., differences in the number or distribution of

relevant tactile receptors) or central nervous system processing of tactile

receptor signals (a more detailed explanation is provided in section 6.1.2).

Sexual desire, however, is likely to be controlled by CNS mechanisms,

suggesting that central nervous system processing of tactile information

may account for the association between tactile sensation and sexual

desire, and possibly sexual arousal.

Cognitive factors could explain the association between sexual

desire and arousal, and tactile sensation. It is well-established in the

sexuality literature that cognitive factors such as attentional focus,

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performance demand, and distraction affect sexual functioning (Cranston-

Cuebas & Barlow, 1990). Distraction can interfere with sexual arousal by

leading the attentional focus away from external sexual cues and stimuli

(Barlow, 1986), a process sometimes referred to as ‘spectatoring’

(Masters & Johnson, 1970). Studies indicate that cognitive distraction

interferes with sexual arousal in normally functioning men (Geer & Fuhr,

1976) and women (Elliott & O'Donohue, 1997), and that self-focused

attention that leads to anxiety provoking thoughts disrupts sexual arousal

(Barlow, 1986). Distraction and self-focus may also interfere with

conscious perception of tactile stimulation such that the psychological

threshold for tactile stimuli is increased. That is, it is possible that the

CNS processing of sexually relevant tactile stimuli (e.g., kissing and

caressing) and non-sexually relevant tactile stimuli (e.g., tactile stimuli in

the tactile examination) is altered in women who are distracted and/or self-

focused, such that they require greater tactile stimulation before conscious

perception occurs.

The finding that neither finger nor lip thresholds were significantly

associated with orgasm functioning among the fluoxetine and control

groups is consistent with the findings from Study 1. This suggests that

neither finger nor lip punctate sensation is associated with orgasm

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problems among women with clinically significant orgasm dysfunction, and

among women with antidepressant-induced orgasm dysfunction.

6.3 Limitations

One of the primary limitations of both Study 1 and Study 2 was that

only one type of cutaneous sensation was measured, punctate sensation.

It is possible that some types of cutaneous sensation, such as vibrotactile,

temperature, and pain sensation, are associated with sexual dysfunction,

while others are not. In addition, only finger and lip threshold were

measured in this dissertation. Given that the behavioral outcome being

studied was sexual functioning, it must be considered a limitation of this

dissertation that genital measures of cutaneous sensation were not

obtained. To my knowledge, no studies have reported the correlation

between finger, lip, and genital sensation. Pukall (personal

communication), however, examined the 1, 3, 6, and 9 o’clock regions of

the vaginal vestibule as well as the thigh, labia minor, deltoid, forearm,

and tibia and found that the deltoid and tibia (r = .58, p< 0.01), deltoid and

vaginal vestibule site 1 (r = .45, p< 0.05), forearm and tibia (r = .51, p<

0.05), labia minor and vestibular site 1 (r = .47, p< 0.05), and vestibular

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site 1 and 6 (r = .66, p = .001) were significantly correlated. This suggests

that non-genital and genital regions tend not be significantly correlated.

Study 2 was limited by the lack of significant declines in sexual

desire functioning among fluoxetine participants. In this dissertation, the

control group exhibited significant improvements in sexual desire, while

the fluoxetine group did not exhibit significant changes in sexual desire.

Problems with sexual desire are a common side effect of fluoxetine

treatment (Feiger et al., 1996; Meston & Gorzalka, 1992; Montejo-

Gonzalez et al., 1997; Patterson, 1993; Pearlstein & Stone, 1994;

Preskorn, 1995), and thus for the medication manipulation to be

successful, the fluoxetine group would need to exhibit significant declines

in sexual desire, rather than simply significantly different changes from the

control group.

Study 2 also was limited by the lack of placebo control, random

assignment, and double-blind design. Instead, the participants were

assigned to the medication condition if they sought antidepressant

treatment (at the University of Texas Counseling and Mental Health

Center), and to the control condition if they indicated clinically significant

depression, but no interest in using antidepressant treatment (as part of

an Introduction to Psychology experimental requirement). That is,

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participants from the medication group were seeking treatment for

depression while participants from the control group were experiencing

similar levels of depression (as measured by clinical interview and the

BDI) but were not actively seeking treatment. It is possible that despite

efforts to find an appropriately matched control group, the two groups

were not ultimately equivalent. In particular, the fluoxetine group was

seeking treatment, while the control group explicitly indicated a lack of

interest in medication treatment. The fluoxetine group may have had

different expectations and hopes than the control group. Without a

placebo control, such medication expectancies were not controlled for.

6.4 Directions for Future Research and Clinical Implications

6.4.1 Directions for Future Research and Clinical Implications:

Tactile Sensitivity and Sexual Dysfunction

Future studies will need to examine whether tactile sensitivity

measures are useful in differentiating women with different types of sexual

problems. Study 1 and Study 2 found an association between arousal

functioning and tactile sensation in FSAD women and depressed women

receiving fluoxetine treatment, and Study 2 found an association between

sexual desire and tactile sensation. It is possible that tactile sensitivity

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may also be associated with clinically diagnosed desire disorders, such as

Hypoactive Sexual Desire Disorder or Sexual Aversion Disorder, as well

as other DSM-IV-TR sexual disorders, such as situational type FOD,

Dyspareunia, and Vaginismus. To my knowledge, only one other study

has examined cutaneous sensation in women with other types of sexual

dysfunction. Pukall, Binik, Khalife, Amsel, and Abbott (2002) noted that

women with a specific form of dyspareunia (sexual pain), known as vulvar

vestibulitis, have significantly more sensitive tactile and pain thresholds

than normally functioning women. Taken together, this indicates that

overly sensitive cutaneous sensation may lead to sexual pain, while

inadequate cutaneous sensation may lead to impaired desire and/or

arousal functioning, suggesting an optimal ‘U’ curve of tactile sensitivity.

Future studies should also examine tactile sensitivity

measurements in dual diagnosis cases, particularly given that many

women with sexual dysfunction experience problems in two or more areas

of sexual functioning (Meston, 2003). In dual diagnosis cases, it is

important to evaluate whether one of the disorders is primary, and whether

the other(s) may be secondary (i.e., resulting from the primary disorder,

and often disappearing once the primary disorder is treated). It is possible

that in some dual diagnosis cases FSAD is the primary disorder and in

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others the secondary disorder, and that tactile sensation threshold is

impaired in women where the FSAD is primary, but not where the FSAD is

secondary. Even when women meet DSM-IV-TR criteria for only one

disorder, they may nonetheless experience sub-clinical problems in

another area of sexual functioning. For example, many of the participants

in Study 1 met DSM-IV-TR criteria for FOD and reported sub-clinical

problems with arousal, but an association between FOD and tactile

sensation was not found. By contrast, in Study 2 an independent

association was found between sexual desire and finger threshold, and

this association could not be accounted for by comorbidity of sexual desire

and arousal problems in these participants. This suggests that despite

high comorbidity or sexual problems, tactile measurements may be useful

in differentiating patients with sexual desire, arousal, and orgasm

problems, and may be useful in determining whether a sexual problem

meets DSM-IV-TR criteria or is sub-clinical.

Future studies will need to examine whether tactile sensitivity

measures are useful in differentiating between women with different

subtypes of FSAD, such as psychologically versus physiologically based

FSAD, and/or those subtypes proposed by Basson (2002; e.g.,

generalized, genital, missed, dysphoric, and anhedonic subtypes).

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Psychological factors such as relationship distress, which may interfere

with normal arousal functioning, seem unlikely to explain the association

between tactile sensation and FSAD. Alternatively, psychological factors

such as anxiety-related distraction and/or depression-related distraction,

which are likely to interfere with normal arousal functioning, may explain

the association between tactile sensation and FSAD. Physiological

factors, such as reduced density of tactile receptors, or reduced blood flow

to both tactile receptors and vaginal capillaries, also may explain the

association between tactile sensation and FSAD. Nonetheless, subtypes

of FSAD have yet to be empirically supported, and thus studies will need

to be conducted to determine whether these diagnostic categories are

empirically supported, and whether tactile sensitivity measurements

differentiate between these subtypes.

Future studies will need to examine the degree to which anxiety

and cognitive distraction accounts for the association between sexual

desire and arousal dysfunction and tactile sensation. Previous

researchers examining the association between anxiety, cognitive

distraction, and sexual dysfunction have used techniques such as a

dichotic listening task (Geer & Fuhr, 1976), a sentence completion task

(Beck, Barlow, Sakheim, & Abrahamson, 1987), and/or electric shock

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(Beck et al., 1987). Future studies could employ some of these same

techniques to evaluate the affects of distraction on tactile sensation and

sexual functioning among sexually functional and dysfunctional women.

Tactile sensation measurements may have several clinical

applications. Ideally, the assessment of female sexual dysfunction should

involve all domains of sexual functioning, including cognitive,

physiological, and behavioral components, but physiological assessment

techniques such as vaginal photoplethysmography have proven to have

limited diagnostic utility. That is, previous studies have not been

successful in differentiating between sexually functional and sexually

dysfunctional women (e.g., Morokoff & Heiman, 1980). The findings from

this dissertation suggest that tactile sensation measurements show

promise as a physiological assessment tool, as part of a comprehensive

assessment battery. The tactile sensitivity measures used in the present

studies have several advantages over measures such as vaginal

photoplethysmography. Tactile sensitivity was able to differentiate

between sexually functional and FSAD women; 71.4% of FSAD

participants and 76.5% of control participants were correctly classified

using tactile sensitivity threshold as a predictor. In addition, tactile

sensitivity measurements are inexpensive and noninvasive. Before tactile

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sensitivity measures can be used as a physiological assessment tool, we

will need to know whether tactile sensitivity measurements differentiate

between subtypes of sexual dysfunction, dual diagnosis cases, sub-clinical

cases, and subtypes of FSAD, as well as subtypes of other sexual

disorders (e.g., primary versus secondary anorgasmia). In addition, we

will need normative data that includes expected ranges in tactile sensitivity

threshold for each of these sexual functioning groups, sub-categorized

according to factors known to affect tactile sensitivity, such as the age of

the patient (Winn & Putz-Anderson, 1990) and, possibly, health of the

patient (e.g., hypertension; Rosa et al., 1986). Finally, the examination

protocol used in this dissertation was fairly lengthy, and thus not practical

for an assessment tool, but considerably shorter albeit slightly less

accurate tactile threshold assessment protocols are available (e.g., Pukall

et al., 2002) that would be more practical for clinical assessment.

A better understanding of the relationship between tactile sensation

and sexual dysfunction may help elucidate the etiology of sexual

dysfunction, and therefore help in the development of appropriate

treatments. If some types of sexual dysfunction arise from impaired or

highly acute tactile sensitivity, medications which may increase or

decrease sensation thresholds, such as alprostadil or dinoprostone (Neal,

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2002) and/or fluoxetine (Yilmaz et al., 1999), could be effective

treatments. Alternatively, if the association between sexual desire and

arousal, and tactile sensation results from cognitive factors such as

distraction, patients may benefit from psychotherapy. It would be

expected that treatment effectiveness would increase as diagnostic

accuracy increased. If impairments in cutaneous sensation do not directly

cause some types of sexual dysfunction, understanding the relationship

between impaired cutaneous sensation and impaired sexual functioning

may nonetheless help identify the etiology. It is important to note,

however, that this is highly speculative given that few studies have been

published in this area and of these few published, many have not yet been

replicated.

One of the primary limitations of the present studies was that only

one type of cutaneous sensation was measured. Future studies will need

to include a more comprehensive examination of cutaneous sensation.

Studies examining cutaneous sensation in men with premature ejaculation

(Rowland et al., 1993; Xin et al., 1996), and women with vulvar vestibulitis

(Pukall et al., 2002), have measured vibrotactile and pain sensation,

respectively. To my knowledge, no studies have examined all aspects of

cutaneous sensation in a study sample, making it difficult to determine

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whether some types of cutaneous sensation are associated with some

subtypes of sexual dysfunction but not others.

An additional limitation was that only non-genital regions of the

body were examined and thus future studies will need to examine

cutaneous sensation on both genital and non-genital regions of the body.

Xin et al. (1996) examined both genital and non-genital regions of the

body in men with premature ejaculation and found that some genital

regions were associated with premature ejaculation while other genital

regions, and non-genital regions (e.g., the fingers) were not. Pukall et al.

(2002) examined various genital and non-genital regions in women with

vulvar vestibulitis, and found that all genital regions, but only some non-

genital regions were associated with increased tactile and pain thresholds.

In this dissertation, cutaneous sensation on non-genital regions was

associated with FSAD, but not FOD. Whether cutaneous sensation on

genital regions may be relevant for diagnosing orgasm disorders warrants

investigation.

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6.4.2 Directions for Future Research and Clinical Implications:

Fluoxetine, Tactile Sensitivity, and Sexual Dysfunction

The findings from the Study 2 suggest that tactile sensation does

not mediate fluoxetine-induced sexual dysfunction among depressed

women. Future studies will need to consider one of two explanations for

these findings. First, that tactile sensation mediates fluoxetine-induced

sexual dysfunction but measures of punctate sensation on the fingers and

lips will not detect this association. Thus, it will be important that future

studies conduct a comprehensive examination of tactile sensation (e.g.,

measures of tactile sensation, such as vibrotactile, pain, or temperature

sensation, and nerve conduction velocity on genital and non-genital tissue)

so that its role in fluoxetine-induced sexual dysfunction can be more

clearly identified. Second, that tactile sensation does not mediate

fluoxetine-induced sexual dysfunction. Thus, future studies will need to

consider alternative explanations for fluoxetine-induced sexual

dysfunction.

It is possible that fluoxetine produces sexual side effects as a result

of its vasoactive properties. A fair amount of evidence supports this

hypothesis. Chronic SSRI-use produces a decrease in platelet and

plasma 5-HT (Bourdeaux et al., 1998; Stahl, 1985) and it is possible that

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this could lead to sexual problems. To my knowledge, no studies have

been published reporting that SSRIs alter vascular functioning in

previously healthy individuals, but SSRIs have been reported to

exacerbate vascular disease (Fricchione, Woznicki, Klesmer, & Vlay,

1993; Skop & Brown, 1996). It has been suggested that serotonin may

be involved in the maintenance of the vascular endothelium (D’Amore &

Shepro, 1982), and if circulating 5-HT levels were altered it is possible that

normal maintenance of the vascular endothelium could be disrupted. One

study that examined rats found that chronic serotonin administration

produced a degeneration of the vascular endothelium (Munsat, Hudgson,

& Johnson, 1977). When the vascular endothelium is damaged it is

subject to exacerbated vasoconstriction (Skop & Brown, 1996). Excessive

vasoconstriction could prevent vasocongestion of the genital tissue

thereby disrupting the processes of vaginal lubrication and possibly

orgasm. It is possible that chronic SSRI-use produces mild degradation of

the vascular endothelium that is sufficient enough to reduce

vasocongestion to the genital tissue but that is not severe enough to

produce vascular problems likely to attract medical attention in otherwise

healthy individuals.

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It is also possible that chronic SSRI-use produces a change in

peripheral 5-HT receptor density and/or sensitivity in a manner similar to

changes noted in the CNS (Meston & Gorzalka, 1992). If receptor density

and/or sensitivity were altered, it would be expected that acute changes in

5-HT activity would produce a blunted or exacerbated effect compared to

what is normally produced by increases or decreases in acute 5-HT

activity. Sexual functioning could be affected by such changes.

Adrenergic stimulation has been reported to produce an increased release

of 5-HT from the enterochromaffin cells of the gastrointestinal tract

(Ahlman & Dahlstrom, 1983; Ahlman, Dahlstrom, Kewenter, & Lundberg,

1976; Larsson, Dahlstrom, Pettersson, Larsson, Kewenter, & Ahlman,

1980; Racke, Schworer, & Kilbinger, 1988) and in women adrenergic

activity facilitates sexual arousal (e.g., Meston & Gorzalka, 1996b). It is

possible that increased adrenergic activity during sexual stimulation in

women produces an acute increase in blood 5-HT. If platelet or

endothelial 5-HT receptor density or sensitivity was altered, acute

increases in circulating 5-HT could produce a transitory change in vascular

functioning, which could impair sexual functioning.

If SSRIs produce sexual side affects by impairing vasocongestion

to the genital region, it would be expected that pharmacologic agents that

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increase blood flow to the genital region would improve sexual functioning.

Indeed, several anecdotal reports and studies have found that sildenafil (a

drug designed to treat erectile failure by increasing blood flow into the

penile tissue) was successful in reversing SSRI-induced sexual

dysfunction in both men and women (Ashton, 1999; Ashton & Bennett,

1999; Nurnberg, Hensley, Lauriello, Parker, & Keith, 1999; Nurnberg,

Lauriello, Hensley, Parker, & Keith, 1999;Schaller & Behar, 1999).

Sildenafil acts to increase blood flow into the genital tissue by facilitating c-

GMP activity that is initiated by nitric oxide (Boolell, Gepi-Attee, Gingell, &

Allen, 1996) and preliminary evidence suggests that the SSRIs may cause

sexual difficulties by inhibiting nitric oxide synthase (Finkel, Laghrissi-

Thode, Pollock, & Rong, 1996; Sussman & Ginsberg, 1998). Taken

together, this suggests that antidepressant-induced sexual side effects

may be treated with pharmacologic agents designed to facilitate genital

blood flow.

6.5 Conclusions

The findings from Study 1 and Study 2 suggest that tactile

sensitivity threshold shows promise as a measurement tool for

differentiating sexual functional and dysfunctional women. Most notably,

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measures of finger threshold were associated with sexual arousal

problems in both studies, among women with clinically significant FSAD,

and clinically depressed women receiving fluoxetine treatment. In

addition, finger threshold was associated with sexual desire problems

among clinically depressed women receiving fluoxetine treatment. Taken

together, the findings from the two studies suggest that further research is

warranted, to further characterize the role of tactile sensitivity in female

sexual disorders, and to determine whether it may be used as a

physiological assessment tool for female sexual dysfunction.

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Appendix A

Beck Depression Inventory (BDI)

The following questionnaire consists of 21 groups of statements. After reading each group of statements carefully, choose the statement that best describes how you’ve been feeling over the past two weeks. Be sure to read all the statements in each group before making your choice. 1.

0) I do not feel sad 1) I feel sad. 2) I am sad all the time and I can’t snap out of it. 3) I am so sad or unhappy that I can’t stand it.

2.

0) I am not particularly discouraged about the future. 1) I feel discouraged about the future. 2) I feel I have nothing to look forward to. 3) I feel that the future is hopeless and that things cannot improve.

3. 0) I do not feel like a failure. 1) I feel like I have failed more than the average person. 2) As I look back on my life, all I can see is a lot of failures. 3) I feel I am a complete failure as a person.

4.

0) I get as much satisfaction out of things as I used to. 1) I don’t enjoy things the way I used to. 2) I don’t get real satisfaction out of anything anymore. 3) I am dissatisfied or bored with everything.

5.

0) I don’t feel particularly guilty. 1) I feel guilty a good part of the time. 2) I feel quite guilty most of the time. 3) I feel guilty all of the time.

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6. 0) I don’t feel I am being punished. 1) I feel I may be punished. 2) I expect to be punished. 3) I feel I am being punished.

7.

0) I don’t feel disappointed in myself. 1) I am disappointed in myself. 2) I am disgusted with myself. 3) I hate myself.

8.

0) I don’t feel I am any worse than anybody else. 1) I am critical of myself for my weaknesses or mistakes. 2) I blame myself all the time for my faults. 3) I blame myself for everything bad that happens.

9.

0) I don’t have any thoughts of killing myself. 1) I have thoughts of killing myself but I would not carry them out. 2) I would like to kill myself. 3) I would kill myself if I had the chance.

10.

0) I don’t cry any more than usual. 1) I cry more now than I used to. 2) I cry all the time now. 3) I used to be able to cry, but now I can’t cry even though I want to.

11.

0) I am no more irritated now than I ever am. 1) I get annoyed or irritated more easily than I used to. 2) I feel irritated all the time now. 3) I don’t get irritated at all by the things that used to irritate me.

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12. 0) I have not lost interest in other people. 1) I am less interested in other people than I used to be. 2) I have lost most of my interest in other people. 3) I have lost all my interest in other people.

13.

0) I make decisions about as well as I ever could. 1) I put off making decisions more than I used to. 2) I have greater difficulty in making decisions than before. 3) I can’t make decisions at all anymore.

14.

0) I don’t feel I look any worse than I used to. 1) I am worried that I am looking old or unattractive. 2) I feel that there are permanent changes in my appearance that

make me look unattractive. 3) I believe that I look ugly.

15.

0) I can work about as well as before. 1) It takes extra effort to get started at doing something. 2) I have to push myself very hard to do anything. 3) I can’t do any work at all.

16.

0) I can sleep as well as usual. 1) I don’t sleep as well as I used to. 2) I wake up 1-2 hours earlier than usual and find it hard to get back to

sleep. 3) I wake up several hours earlier than I used to and cannot get back

to sleep. 17.

0) I don’t get more tired than usual. 1) I get tired more easily than I used to. 2) I get tired from doing almost anything. 3) I am too tired to do anything.

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18. 0) My appetite is no worse than usual. 1) My appetite is not as good as it used to be. 2) My appetite is much worse now. 3) I have no appetite at all anymore.

19.

0) I haven’t lost much weight, if any lately 1) I have lost more than 5 pounds. 2) I have lost more than 10 pounds. 3) I have lost more than 15 pounds.

20.

0) I am no more worried about my health than usual. 1) I am worried about physical problems such as aches and pains; or

upset stomach; or constipation. 2) I am very worried about physical problems and it’s hard to think of

much else. 3) I am so worried about my physical problems that I cannot think

about anything else. 21.

0) I have not noticed any recent change in my interest in sex. 1) I am less interest in sex than I used to be. 2) I am much less interested in sex now. 3) I have lost interest in sex completely.

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Appendix B

Beck Anxiety Inventory (BAI)

Below is a list of common symptoms of anxiety. Please read each item in the list carefully. Indicate HOW MUCH you have been bothered by each symptom during the PAST WEEK, INCLUDING TODAY using the scale shown below. Choose the answer closest to true where the question is not fully applicable. 0 = Not at all 1 = Mildly (It did not bother me much) 2 = Moderately (It was very unpleasant but I could stand it) 3 = Severely (I could barely stand it) 1) Numbness or tingling _____ 2) Feeling hot _____ 3) Wobbliness in legs _____ 4) Unable to relax _____ 5) Fear of the worst happening _____ 6) Dizzy or lightheaded _____ 7) Heart pounding or racing _____ 8) Unsteady _____ 9) Terrified _____ 10) Nervous _____ 11) Feelings of choking _____ 12) Hands trembling _____ 13) Shaky _____ 14) Fear of losing control _____ 15) Difficulty breathing _____ 16) Fear of dying _____ 17) Scared _____ 18) Indigestion or discomfort in abdomen _____ 19) Faint _____ 20) Face flushed _____ 21) Sweating (not due to heat) _____

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Appendix C

Derogatis Sexual Functioning Inventory (DSFI)

Body Image Scale

This questionnaire contains several statements about how you typically view your body. Using the scale as shown below, circle a number on the answer sheet that most accurately reflects your real private opinion about yourself. (PLEASE NOTE: Both women and men should answer statements 1 to 10, however, statements 11 -16 apply TO WOMEN ONLY, and statements 17-22 apply TO MEN ONLY).

1 = not at all 2 = slightly 3 = moderately 4 = quite a bit 5 = extremely

BOTH MEN AND WOMEN 1. I am less attractive than I would like to be. 2. I am too fat. 3. I enjoy being seen in a bathing suit. 4. I am too thin. 5. I’d be embarrassed to be seen nude by a lover. 6. I am too short. 7. There are parts of my body I don’t like at all. 8. I am too tall. 9. I have too much body hair. 10. My face is attractive. WOMEN ONLY 11. I have a shapely and well-proportioned body. 12. I have attractive breast. 13. Men would find my body attractive. 14. I have attractive legs. 15. I am pleased with the way my vagina looks. 16. Men tend to think of me as “sexy.”

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MEN ONLY 17. I have a well-proportioned body. 18. I am satisfied with the size of my penis. 19. Women would find my body attractive. 20. I am well-coordinated and athletic. 21. I am pleased with the physical condition of my body. 22. Women tend to think of me as “sexy.”

DSFI Drive

Circle a number on the answer sheet to indicate how often you typically engaged in the following activities during the past year: 0 = not at all 1 = once a month or less 2 = 1-2 times a month 3 = once a week 4 = 2-3 times a week 5 = 406 times a week 6 = once a day 7 = 2-3 times a day 8 = 4 or more times a day 1. Intercourse 2. Kissing and petting 3. Masturbation 4. Sexual fantasies 5. Romantic fantasies 6. What would be your ideal frequency of sexual intercourse?

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DSFI Sexual Experience

Below are different sexual experiences that people have. We would like to know which of these sexual behaviors you have experienced. Please indicate those experiences you have personally had by circling a “Y” (for Yes) on the answer sheet. If you have not had the experience circle “N” (for No) on the answer sheet. Please check the answer sheet to be sure all items in this section have been answered (i.e., please don’t skip any). 1. Male lying prone on female (clothed) 2. Stroking or petting your sexual partner’s genitals 3. Erotic embrace (clothed) 4. Masturbating alone 5. Having genitals caressed by your sexual partner 6. Kissing of sensitive (non-genital) areas of the body 7. Breast petting (clothed) 8. Having your genitals orally stimulated 9. Your anal area caressed by your sexual partner 10. Mutual undressing of each other 11. Mutual petting of genitals to orgasm 12. Caressing your sexual partner’s anal area 13. Kissing on the lips 14. Deep kissing 15. Oral stimulation of your partner’s genitals 16. Mutual oral stimulation of genitals 17. Breast petting (nude) 18. Male kissing female’s nude breasts 19. Vaginal intercourse, male superior (on top) position 20. Vaginal intercourse, female superior (on top) position 21. Vaginal intercourse, entry from behind position 22. Anal intercourse 23. Vaginal intercourse, side by side position 24. Vaginal intercourse, sitting position

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Appendix D

Female Sexual Function Index (FSFI)

INSTRUCTIONS: These questions ask about your sexual feelings and responses during the past 4 weeks. Please answer the following questions as honestly and clearly as possible. In answering these questions the following definitions apply: Sexual activity includes intercourse, caressing, foreplay, and masturbation. Sexual intercourse is defined as penile penetration (entry) of the vagina. Sexual stimulation includes situations like foreplay with a partner, self-stimulation (masturbation), or sexual fantasy. CIRCLE ONLY ONE CHOICE PER QUESTION: Sexual desire or interest is a feeling that included wanting to have a sexual experience, feeling receptive to a partner’s sexual initiation, and thinking or fantasizing about having sex.

1. Over the past 4 weeks, when sexual activity was possible, how often did you feel sexual desire or interest?

a. Almost always or always b. Most times(much more than half the time) c. Sometimes (about half the time) d. A few times (much les than half the time) e. Almost Never

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2. Over the past 4 weeks, how would you rate your level (degree) of sexual desire or interest?

a. Very high b. High c. Moderate d. Low e. Very low or none at all 3. Over the past 4 weeks, how often did you feel sexually aroused

(“turned on”) during sexual activity or intercourse? a. No sexual activity b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never

4. Over the past 4 weeks, how would you rate your level of sexual

arousal (“turn on”) during sexual activity or intercourse? a. No sexual activity b. Very high c. High d. Moderate c. Low d. Very low or none at all 5. Over the past 4 weeks, how confident were you about becoming

sexually aroused during sexual activity or intercourse? a. No sexual activity b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never

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6. Over the past 4 weeks, how often have you been satisfied with your arousal (excitement) during sexual activity or intercourse?

a. No sexual activity b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never 7. Over the past 4 weeks, how often did you become lubricated (“wet”)

during sexual activity or intercourse? a. No sexual activity b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never 8. Over the past 4 weeks, how difficult was it to become lubricated

(“wet”) during sexual activity or intercourse? a. No sexual activity b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never 9. Over the past 4 weeks, how often did maintain your lubrication

(“wetness”) during completion of sexual activity or intercourse? a. No sexual activity b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never

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10. Over the past 4 weeks, how would you rate your amount of lubrication (“wetness”) during completion of sexual activity or intercourse?

a. No sexual activity b. Very high c. High d. Moderate e. Low f. Very low or none at all g. Don’t Know 11. Over the past 4 weeks, when you had sexual stimulation or

intercourse, how often did you reach orgasm (climax)? a. No sexual activity b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never 12. Over the past 4 weeks, when you had sexual stimulation or

intercourse, how difficult was it for you reach orgasm (climax)? a. No sexual activity b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never 13. Over the past 4 weeks, how satisfied were you with your ability to

reach orgasm (climax) during sexual activity or intercourse? a. No sexual activity b. Very satisfied c. Moderately satisfied d. About equally satisfied and dissatisfied e. Moderately dissatisfied f. Very dissatisfied

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14. Over the past 4 weeks, how satisfied have you been with the amount

of emotional closeness during sexual activity between you and your partner?

a. No sexual activity b. Very satisfied c. Moderately satisfied d. About equally satisfied and dissatisfied e. Moderately dissatisfied f. Very dissatisfied 15. Over the past 4 weeks, how satisfied have you been with your sexual

relationship with your partner? a. Very satisfied b. Moderately satisfied c. About equally satisfied and dissatisfied d. Moderately dissatisfied e. Very dissatisfied 16. Over the past 4 weeks, how satisfied have you been with your overall

sexual life? a. Very satisfied b. Moderately satisfied c. About equally satisfied and dissatisfied d. Moderately dissatisfied e. Very dissatisfied 17. Over the past 4 weeks, how often did you experience discomfort or

pain during vaginal penetration? a. Did not attempt intercourse b. Almost always or always c. Most times d. Sometimes (about half the time) e. A few times (much les than half the time) f. Almost Never or never

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18. Over the past 4 weeks, how often did you experience discomfort or pain following vaginal penetration?

g. Did not attempt intercourse h. Almost always or always i. Most times j. Sometimes (about half the time) k. A few times (much les than half the time) f. Almost Never or never 19. Over the past 4 weeks, how would you rate your level (degree) of

discomfort or pain during vaginal penetration? a. Very high b. High c. Moderate d. Low e. Very low or none at all

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Appendix E

Female Sexual Satisfaction Scale (FSSS)

On the answer sheet, please indicate your level of agreement of disagreement with each statement below, according to the scale shown below. 1 = strongly disagree 2 = disagree a little 3 = neither agree or disagree 4 = agree a little 5 = strongly agree 1. I feel content with the way my present sex life is (or with the sexual

aspect of my present relationship). 2. I often feel something is missing from my present sex life (or from the

sexual aspect of my present relationship). 3. I often feel I don’t have enough emotional closeness in my sex life (or

in the sexual aspect of my present relationship). 4. I often feel II don’t’ have enough variety or experimenting in my sex life

(or in the sexual aspect of my present relationship). 5. I feel content with how often I presently have sexual intimacy

(intercourse, etc.) in my life (or in my present relationship). 6. I don’t have any important problems or concerns about sex (arousal,

orgasm, frequency, compatibility, communication, etc.). Please answer the remaining items with reference to your present relationship partner. If you are not currently involved in a close relationship, simply answer them with reference to your most recent close relationship. 7. My partner and I do not discuss sex openly enough with each other, or

do not discuss sex often enough. 8. I usually feel completely comfortable discussing sex whenever my

partner wants to. 9. my partner usually feels completely comfortable discussing sex

whenever I want to. 10. I have no difficulty talking about my deepest feelings and emotions

when my partner wants me to.

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11. My partner has no difficulty talking about their deepest feelings and emotions when I want them to.

12. My partner always gets defensive any time I try discussing sex. 13. I often feel upset about my partner wanting sexual intimacy more often

than I do. 14. I often feel upset about my partner not wanting sexual intimacy more

often than I do. 15. I often feel my partner isn’t sensitive or aware enough about my sexual

likes and desires. 16. I often feel that my partner and I are not sexually compatible enough. 17. I often feel that my partner’s beliefs and attitudes about sex are too

different from mine. 18. I often feel my partner isn’t tolerant or understanding enough about my

sexual anxieties or insecurities. 19. I often feel that my partner isn’t physically attracted to me enough. 20. I sometimes feel I am not physically attracted to my partner enough. 21. I often feel concerned about my lack of desire or interest in sex. 22. I’m concerned that my occasional problems becoming aroused could

occur again or become worse. 23. I’m concerned about my difficulty reaching orgasm with my partner. 24. I’m concerned about my partner’s difficulty reaching orgasm with me. 25. Too often I feel like I’m a poor or inadequate lover for my partner. 26. I often wish my partner would be a lot more adventurous and open-

minded during sex. 27. I often wish my partner would be a lot more loving and tender during

sex. 28. Overall, how satisfactory or unsatisfactory is your present sex life?

1 = not at all satisfactory 2 = not very satisfactory 3 = reasonably satisfactory 4 = very satisfactory 5 = completely satisfactory

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Appendix F

Medical Information Questionnaire

Some of the following questions cover material that is sensitive and personal. Your responses will be kept completely confidential. If you are unable or do not wish to answer any question, you may leave it blank. 1. Are you currently taking antidepressant medication (for example, Prozac, Paxil,

Zoloft, Anafranil, Effexor, or Serzone)? Yes ____ No ____

If yes, for how long: _____ months _____ weeks _____ days

If yes, please fill in the name: ________________________ 2. If no, have you taken antidepressant medication during the past 6 months? Yes ____ No ____ 3. If you are currently taking an antidepressant medication or have taken one in the

past 6 months, please fill in the following information: Drug name: _____________________________ Dosage; _____ mg/per day 4. Are you currently taking any other medication? Yes ____ No ____ 5. If yes, please fill in: ___________________________ Dosage _____ mg/per day ___________________________ Dosage _____ mg/per day ___________________________ Dosage _____ mg/per day ___________________________ Dosage _____ mg/per day 6. Do you have a history of high blood pressure? Yes ____ No ____ 7. If no, do you have a history of low blood pressure? Yes ____ No ____ 8. What is your gender? Male ____ Female ____ 9. How old are you? ______ years old. 10. How tall are you? ______ feet ______ inches 11. Approximately how much do you weigh? ______ pounds 12. Do you smoke? Yes ____ No ____ If yes, how many cigarettes per week? ____

174

13. Do you drink alcohol? Yes ____ No ____

If yes, how many drinks per week? ____ 14. Do you have diabetes? Yes ____ No ____ 15. Do you have a history of Thyroid disease? Yes ____ No ____ 16. For females only: How many days ago did your last menstrual start? ____ finish? ____ Are you menstrual cycles usually regular? Yes ____ No ____ How many days does your typical menstrual cycle last? ____ Are you taking birth control pills? Yes ____ No ____

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Appendix G

Orgasmic Functioning Questionnaire (OFQ)

1. What % of the time does each of the following sexual activities listed below resulting in orgasm (for you)? Example: If 8 out of every 10 times you try masturbating to orgasm, you achieve orgasm, you would write “80%” in the space on the answer sheet. If you have tried but not achieved orgasm that way, you would write “0%.” If you have not tried to achieve orgasm that way, you would simply write “N/A.” _____ a. masturbation _____ b. manual stimulation by partner _____ c. oral stimulation by partner _____ d. intercourse _____ e. intercourse & manual stimulation by self or partner 2. What is the most number of orgasms you’ve had in one day? _____

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Appendix H

Sexual Functioning Index (SFI)

Some of the following questions cover material that is sensitive and personal. Your responses will be kept completely confidential. If you are unable or do not wish to answer any question, you may leave it blank.

Answer the following questions by choosing the most accurate response for the past month (except for question #9). 1. Are you currently involved in a sexual relationship? Yes ____ No ____ If yes, for how long? _____ months. 2. During the past month, how frequently have you had sexual thoughts, fantasies,

or erotic dreams? (Please place an “x” next to the most appropriate response.) ____ (0) not at all ____ (1) once ____ (2) 2 or 3 times ____ (3) Once a day ____ (4) More than once a day 3. Using the scale to the right, indicate how frequently you have felt a desire to

engage in the following activities during the past month? (Please place an answer next to each item, even if it may not apply to you.)

kissing ___________ (0) not at all masturbation alone ___________ (1) once mutual masturbation ___________ (2) 2 or 3 times petting and foreplay ___________ (3) once a day oral sex ___________ (4) more than once a day vaginal penetration or intercourse ___________ anal sex ___________ 4. Using the scale to the right, indicate how frequently you have become aroused

by the following sexual experiences during the past month? (Please place an answer next to each item, even if it may not apply to you.)

kissing ___________ (0) not at all masturbation alone ___________ (1) once mutual masturbation ___________ (2) 2 or 3 times petting and foreplay ___________ (3) once a day oral sex ___________ (4) more than once a day vaginal penetration or intercourse ___________ anal sex ___________

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5. During the past month, who has usually initiated sexual activity. (Please place an “x” next to the most appropriate response.)

____ (0) I have not had sex with a partner during the past week ____ (1) I usually have initiated activity ____ (2) My partner and I have equally initiated activity ____ (3) My partner usually has initiated activity 6. During the past month, have you felt pleasure from any forms of sexual

experience? (Please place an “x” next to the most appropriate response.) ____ (0) Have had no sexual experience during the past week ____ (1) Have not felt any pleasure ____ (2) Seldom, less than 25% of the time ____ (3) Sometimes, about 50% of the time ____ (4) Usually, about 75% of the time ____ (5) Always felt pleasure 7. Using the scale to the right, indicate how often you have reached orgasm during

the past month with the following activities? (Please place an answer next to each item, even if it may not apply to you.)

Kissing ___________ (0) Have not engaged in

this activity Masturbation alone ___________ (1) Not at all Mutual masturbation ___________ (2) Seldom, less than 25% of the time Petting and foreplay ___________ (3) Sometimes, about 50% of the time Oral sex ___________ (4) Usually, about 75% of the time Vaginal penetration or intercourse ___________ (5) Always felt pleasure Anal sex ___________ 8. Using the scale to the right, during the past month, how frequently have you

experienced the following? (Please place an answer next to each item, even if it may not apply to you.)

Lack of vaginal lubrication ___________ (0) Not at all Painful penetration or intercourse ___________ (1) Seldom, less than 25% of the time Difficulty reaching orgasm ___________ (2) Sometimes, about 50% of the time Vaginal tightness ___________ (3) Usually, about 75% of the time Vaginal “numbness” ___________ (4) Always

178

9. Using the scale to the right, during the past 6 months, how frequently have you experienced the following? (Please place an answer next to each item, even if it may not apply to you.)

Lack of vaginal lubrication ___________ (0) Not at all Painful penetration or intercourse ___________ (1) Seldom, less than 25% of the time Difficulty reaching orgasm ___________ (2) Sometimes, about 50% of the time Vaginal tightness ___________ (3) Usually, about 75% of the time Vaginal “numbness” ___________ (4) Always 10. Over the past month, how satisfied have you been with your sexual relationship

with your partner? (Please place an “x” next to the most appropriate response.) ____ (0) Not currently in a sexual relationship ____ (1) Very satisfied ____ (2) Somewhat satisfied ____ (3) Neither satisfied nor dissatisfied ____ (4) Somewhat dissatisfied ____ (5) Very dissatisfied 11. This past month, how intense or pleasurable would you rate your orgasms as

being? (Please place an answer next to each item, even if it may not apply to you.)

____ (0) I have not had an orgasm this month ____ (1) Not very intense or pleasurable ____ (2) Somewhat intense or pleasurable ____ (3) Very intense and pleasurable 12. Please estimate the length of time it typically takes your partner to ejaculate. a) Prior to penetration b) within just a few seconds of penetration c) <1 minute after penetration (but not immediately after penetration) d) 2-5 minutes after penetration e) 5-10 minutes after penetration f) greater than 10 minutes after penetration

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Appendix I

Modified - Medical Information Questionnaire

Some of the following questions cover material that is sensitive and personal.

Your responses will be kept completely confidential. If you are unable or do not

wish to answer any question, you may leave it blank.

1. Do you smoke? Yes ___ No ___ If yes, how many cigarettes did you

smoke in the past week? _____

2. Do you drink alcohol? Yes ___ No ___ If yes, how many drinks did you

consume in the past week? _____

3.

How many days ago did your last menstruation begin? ____

finish? ____

Are your menstrual cycles usually regular? Yes ___ No ___

How many days does your typical menstrual cycle last? _____

Are you taking birth control pills? Yes ___ No ___

4. If you are currently taking Prozac as part of this study, have you

missed any doses since your last visit? Yes ___ No ___ If yes, how

many days did you miss? _____

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Appendix J

Modified - Orgasmic Functioning Questionnaire

1. What % of the time, in the past week, has each of the following sexual activities listed below resulting in orgasm (for you)? Example: If 8 out of every 10 times you try masturbating to orgasm, you achieve orgasm, you would write “80%” in the space on the answer sheet. If you have tried but not achieved orgasm that way, you would write “0%.” If you have not tried to achieve orgasm that way, you would simply write “N/A.” _____ a. masturbation _____ b. manual stimulation by partner _____ c. oral stimulation by partner _____ d. intercourse _____ e. intercourse & manual stimulation by self or partner 2. If you have attained orgasm by one or more of the preceding means, how long does it generally take to achieve orgasm? (specify means) __________________________________________________________

181

Appendix K

Modified - Sexual Functioning Index

Some of the following questions cover material that is sensitive and personal. Your responses will be kept completely confidential. If you are unable or do not wish to answer any question, you may leave it blank.

Answer the following questions by choosing the most accurate response for the past week (except for question #9). 1. Are you currently involved in a sexual relationship? Yes ____ No ____ If yes, for how long? _____ months. 2. During the past week, how frequently have you had sexual thoughts, fantasies,

or erotic dreams? (Please place an “x” next to the most appropriate response.) ____ (0) not at all ____ (1) once ____ (2) 2 or 3 times ____ (3) Once a day ____ (4) More than once a day 3. Using the scale to the right, indicate how frequently you have felt a desire to

engage in the following activities during the past week? (Please place an answer next to each item, even if it may not apply to you.)

kissing ___________ (0) not at all masturbation alone ___________ (1) once mutual masturbation ___________ (2) 2 or 3 times petting and foreplay ___________ (3) once a day oral sex ___________ (4) more than once a day vaginal penetration or intercourse ___________ anal sex ___________ 4. Using the scale to the right, indicate how frequently you have become aroused

by the following sexual experiences during the past week? (Please place an answer next to each item, even if it may not apply to you.)

kissing ___________ (0) not at all masturbation alone ___________ (1) once mutual masturbation ___________ (2) 2 or 3 times petting and foreplay ___________ (3) once a day oral sex ___________ (4) more than once a day vaginal penetration or intercourse ___________ anal sex ___________

182

5. During the past week, who has usually initiated sexual activity. (Please place an “x” next to the most appropriate response.)

____ (0) I have not had sex with a partner during the past week ____ (1) I usually have initiated activity ____ (2) My partner and I have equally initiated activity ____ (3) My partner usually has initiated activity 6. During the past week, have you felt pleasure from any forms of sexual

experience? (Please place an “x” next to the most appropriate response.) ____ (0) Have had no sexual experience during the past week ____ (1) Have not felt any pleasure ____ (2) Seldom, less than 25% of the time ____ (3) Sometimes, about 50% of the time ____ (4) Usually, about 75% of the time ____ (5) Always felt pleasure 7. Using the scale to the right, indicate how often you have reached orgasm during

the past week with the following activities? (Please place an answer next to each item, even if it may not apply to you.)

Kissing ___________ (0) Have not engaged in this activity Masturbation alone ___________ (1) Not at all Mutual masturbation ___________ (2) Seldom, less than 25% of the time Petting and foreplay ___________ (3) Sometimes, about 50% of the time Oral sex ___________ (4) Usually, about 75% of the time Vaginal penetration or intercourse ___________ (5) Always felt pleasure Anal sex ___________ 8. Using the scale to the right, during the past week, how frequently have you

experienced the following? (Please place an answer next to each item, even if it may not apply to you.)

Lack of vaginal lubrication ___________ (0) Not at all Painful penetration or intercourse ___________ (1) Seldom, less than 25% of the time Difficulty reaching orgasm ___________ (2) Sometimes, about 50% of the time Vaginal tightness ___________ (3) Usually, about 75% of the time Vaginal “numbness” ___________ (4) Always

183

9. Over the past week, how satisfied have you been with your sexual relationship with your partner? (Please place an “x” next to the most appropriate response.)

____ (0) Not currently in a sexual relationship ____ (1) Very satisfied ____ (2) Somewhat satisfied ____ (3) Neither satisfied nor dissatisfied ____ (4) Somewhat dissatisfied ____ (5) Very dissatisfied 10. This past week, how intense or pleasurable would you rate your orgasms as

being? (Please place an answer next to each item, even if it may not apply to you.)

____ (0) I have not had an orgasm this month ____ (1) Not very intense or pleasurable ____ (2) Somewhat intense or pleasurable ____ (3) Very intense and pleasurable 11. Please estimate the length of time it typically takes your partner to ejaculate. g) Prior to penetration h) within just a few seconds of penetration i) <1 minute after penetration (but not immediately after penetration) j) 2-5 minutes after penetration k) 5-10 minutes after penetration l) greater than 10 minutes after penetration

184

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VITA

Penelope F. Frohlich was born in Ithaca, New York on June 10,

1970, the daughter of Holly Jane Barnet and Clifford Arnold Frohlich.

After completing her work at Lanier High School, Austin, Texas, in 1988,

she entered The University of Texas in Austin, Texas. During the summer

of 1991, she attended The University of Hawaii. She received the degree

of Bachelor of Arts from The University of Texas in May 1992. During the

following three years she was employed as a high school English teacher

in Samut Sakorn, Thailand, as a farm laborer in rural Israel, and as a

nanny in London, England. In September 1995 she entered the Graduate

School of The University of Texas to pursue a doctoral degree in Clinical

Psychology. In August 1998 she received her Masters of Arts for her work

on rat and primate models of brain injury. She began her study of female

sexuality in September 1998. She has published two first author and five

second author papers examining the role of peripheral physiology,

depression, and antidepressant medication in female sexual dysfunction.

She completed her internship at the Audie L. Murphy Veterans Hospital in

San Antonio, Texas, from August 2001 to August 2002. On April 14th,

2002 she married David Kendrick Jungerman. She is presently employed

as an instructor at Concordia University in Austin, Texas, and is expecting

the birth of her first child in July 2003.

Permanent Address: 3201 Perry Lane, Austin, Texas 78731

This dissertation was typed by the author.

Copyright by Penelope F. Frohlich 2003 - The University of ...

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