Quiz
1. True or False Most women would say periods are
AWESOME!! FALSE
2. True or False ABNORMAL periods are even more
AWESOME!!! FALSE
Definitions
Normal menstrual cycle Interval: 28 +/- 7 days (21-35 days) Can change from cycle to cycle Length </= 7 days Flow: Avg blood loss: 35ml (20-60ml)
Menorrhagia Prolonged – more than 7 days or Heavy – greater than 80ml/day CYCLIC menstruation Aka “hypermenorrhea”
Definitions
Menometrorrhagia Prolonged or heavy with breakthrough
bleeding
Polymenorrhea Bleeding occuring at intervals <21 days
Oligomenorrhea Intervals between bleeding episodes vary
from 35 days to 6 months
It’s Common!
Estimated 10 million women in the US Over 2 million seen each year for
menstrual abnormalities 1/3 of gyn visits Most common cause of emergency gyn
hospital admission Most common reason for hysterectomy Commonly mismanaged!!!
Etiology
Pregnancy Hormonal Imbalance (hypothal/pit/ovary) Hemostatic Disorders (systemic vs local) Reproductive Tract Pathology Iatrogenic
Pregnancy
Ectopic Spontaneous/Incomplete Abortion Gestational Trophoblastic Disease “Normal Pregnancy”
DON’T FORGET THE PREGNANCY TEST (you will look stupid)
Hormonal
Anovulation/Oligo-ovulation PCOS/Obesity
20% PCOS have normal BMI Menarcheal/Perimenarcheal- immature HPA
Fully active in fetal life, suppressed in childhood, and then reactivated
Perimenopausal insensitive ovarian follicles
Hormonal
Anovulation/Oligo-ovulation Thyroid/Prolactin disorder
TRH induced increases in Prolactin- inhibits pulsatile GnRH
Hypothalamic Disorders Anorexia, exercise induced, gonadotropin
deficiency, POF Drugs- hypothalamic depressants, steroids,
herbs Anti-dopaminergic meds- take away inhibitory
dopamine on prolaction- inhibits pulsatile GnRH
Systemic Hemostatic Disorders Inherited disorders
Von Willebrand disease Hemophilias
Acquired disorders ITP/TTP Liver Disease Leukemia
Iatrogenic Anticoagulants ASA/NSAIDS
Iatrogenic Causes
Medications Hormonal Non-hormonal
Procedures D&C
Devices Copper IUD (Paraguard) Levonogestrel IUD (Mirena)
Reproductive Tract Disorders Uterine Lesions
Endometrial polyps Submucosal polyps Endometritis Adenomyosis Hyperplasia or cancer
Anovulation or Oligo-Ovulation Pathophysiology
In a reproductive age patient who is not having regular menses, must determine if 1. Progesterone Deficient 2. Estrogen and Progesterone Deficient
Anovulation or Oligo-Ovulation Patholophysiology
LACK OF PROGESTERONE Estrogen production with lack of
progesterone leads to unopposed estrogen stimulation of the endometrium
Can result in irregular shedding of the endometrium resulting in unscheduled/heavy bleeding
Potential for development of endometrial hyperplasia or cancer.
Anovulation or Oligo-ovulation
Pathophysiology: lack of ESTROGEN and PROGESTERONE
Lack of estrogen AND progestin in reproductive age women can lead to osteoprorosis, increased risk for heart disease, and reduced quality of life
Examples: anorexia nervosa, athletic amenorrhea, premature ovarian failure
Anovulation or Oligo-Ovulation Progestin Challenge
Purpose: Assess endogenous estrogen status of the patient Is there estrogen present
From peripheral conversion (estrone) Or Ovaries
Types: Medroxyprogesterone acetate (Provera, MPA) 10mg
for 10-12 days Progesterone in oil 100-150mg IM Norethindrone acetate (agestin, NETA) 5mg for 10-
12 days
Endometrial Cancer
Most common gynecologic malignancy: est 40,100 cases/ 7,470 deaths in 2008
Most patients between ages of 50-59 25% prior to menopause 5% before age 40 75% stage 1 disease
Endometrial Cancer- Preventable Estrogen Excess!!!!
Perimenopausal with estrogen excess PCOS Obesity Postmenopausal with continued estrogen
production from ovary/peripheral conversion of androstendione to estrone
TREAT WITH PROGESTINS OR PROGESTIN DOMINANT FORMULATIONS (OCs)
Management
Medical management of Profuse Bleeding Very few published randomized trials Estrogen only Progestin only Estrogen + Progestin
Management
Use of IV Premarin in tx of DUB a double blind randomized controlled study
Only randomized trial assessing IV estrogen in tx of acute bleeding
34 randomized to IV placebo solution vs IV conjugated equine estrogen (premarin) 25mg IV q 4 hrs
At 5 hrs, bleeding stopped in 72% in CEE group vs 38% in placebo group (p= 0.021)
DeVore et al: Obstet Gynecol 1982; 59: 286-91
Management
High dose MPA for tx of DUB in 24 Adolescents
Hospitalized for excessive uterine bleeding Given 60-120mg MPA on day one, followed
by 20mg/day x 10 days All stopped bleeding within 4 days
Aust N Z Obstet Gynaecol 1997; 37: 228-31
Management
Oral MPA and Combination OCs for Acute Uterine Bleeding
Presented with acute uterine bleeding requiring emergent medical or surgical intervention
40 subjects randomized to a 7 day treatment of MPA 20mg TID OCPs (1mg NTE/35 mcg EE) TID
Doses reduced to once a day for the next 3 weeks
Management
Patient characteristics: avg age 43, BMI 30, mean hgb 8.0
Only one patient required surgical intervention (D&C for acute bleeding in OCP group)
Median # days to cessation of bleeding: 3 days in both groups
Cessasion of bleeding by 2 week visit in 76% in MPA and 88% in OCP group
Management
Mean satisfaction scores were similar Would use medication again for bleeding
if necessary 81% in MPA group 69% in OCP group
Median scores for bloating/cramping/nausea did not differ
Munro et al Obstet Gynecol 2006; 108: 924-9
Anovulatory bleeding
PROGESTINS!!!!! Progestins alone Combination OCPs Depo Provera (MPA) Clomiphine Citrate (Clomid) or other
ovulation inducing medication if pregnancy desired
Anovulatory Bleeding
Cyclic Progestins MPA 10mg NTE 5mg
Patient instructed to take for 14 days every month. Can decrease interval over time
Anovulatory Bleeding
Cyclic Progestins Warn the patient that bleeding may be
heavy initially but will decrease over time Explain reason for treatment: prevention of
episodic irregular/heavy bleeding and CANCER
Can modify timing of progestin therapy around activities/ events for convenience
Anovulatory Bleeding
OCPs If no bleeding in over a month, consider
progestin withdrawl (NETA 5mg x 12 days) before initiating OCPs to shed thickened endometrium (began OCPs on day 3 of bleeding)
Also effective in treating associated problems (acne, hirsutism)
Anovulatory Bleeding
DMPA (Depo Provera) Menstrual changes occur in almost all users Most experience unpredictable bleeding
patterns in the first few months of use ¼ will discontinue in the 1st yr for irregular
bleeding With continued use, frequency and length
of bleeding episodes decreases with most becoming amenorrheic over time ¼ will not resume regular menses for up to 1 yr
Ovulatory Hypermenorrhea
Uterine bleeding controlled by prostaglandins
Abnormal prostaglandin levels in the endometrium can lead to excessive bleeding Decrease in prostaglandin F2alpha
(vasoconstrictor) and thromboxane (platelet aggregator)
Increase in prostaglandin E2 (vasodilator) and prostacyclin (platelet inhibitor)
Ovulatory Bleeding
NSAIDs OCPs Oral Progestins DMPA Danazol GnRH (Lupron) Anti-fibrinolytic agents Progestin IUD (Mirena)
Ovulatory Bleeding
NSAIDs Several studies show reduction in blood loss Less effective than other medical modalities
Ibuprofen 800mg 3-4 x day Naproxen sodium 550mg 3 x day Mefenamic acid 500mg 3 x day Meclofenamate 100mg 3 x day
Beginning day prior to or first day of menses for 3-5 days
Ovulatory Bleeding
Continuous OCP use (no 7 day break) should be considered as many will have unacceptable withdrawl bleeding if given 21/7
If breakthrough bleeding on continuous OCPs, stop 3 days and then restart (3 day 90% effective in resolving BTB)
Sulak et al Am J Obstet Gynecol 2006; 195: 935-41
Ovulatory Bleeding
Oral Progestins MPA 10-20mg/day or NETA 5-15mg/day Higher doses/longer intervals of cyclic
progestins Required for tx of menorrhagia as compared to
anovulatory bleeding NETA 5mg BID x 21 days starting cyle day #7
Continuous Progestins Without a break NETA 5mg daily starting on day 3 of cycle, don’t take a
break unless breakthrough bleeding, stop 3 days and restart or give in 24/4 fashion for predictable bleeding each month.
Ovulatory Bleeding
DMPA (Depo Provera) Dose 150-250mg IM every 2-3 months Disadvantage- high incidence of irregular
bleeding
Ovulatory Bleeding
GnRH agonists (Lupron) MOA: inhibits ovulation and ovarian steroid
productions, inducing amenorrhea Dose: 3.75mg IM every month or 11.25mg IM
every 3 months Often benefits short term for induction of
amenorrhea and to correct severe anemia Consider simultaneous norethendrone 5mg/d
Disadvantage to long term use Expense Hypoestrogenic state- need for add back for
prevention of side effects
Ovulatory Bleeding
Antifibrinolytics (Tranexamic Acid- Lysteda)
Approved by the FDA in the US in 2009 for tx of heavy menstrual bleeding
Commonly used throughout the world (OTC in some countries)
Effective in reducing menstrual blood loss (50%)
Concern about thromboembolic events has not been substantiated in recent studies
Ovulatory Bleeding
Progestin IUD (mirena) Effective in reducing mean blood loss Approved by FDA for treatment of heavy
menstrual bleeding october 2009 80-90% report reduction in blood loss after
6 months, approx 30% amenorrheic
DUB and Fibroids
NSAIDs Combination OCPs Oral progestins DMPA Dnazol GnRH agonists Antifibrinolytic agents Medicated IUDs Selective Progesterone Receptor Modulators Antiprogestational agents Aromatase inhibitors
Procedures/Surgery
Endometrial Ablation Hysteroscopic resection/ablation Non-hysteroscopic ablation
Uterine Artery Embolization Hysterectomy
Key Points
Many patients are progesterone deficient Most endometrial cancer is preventable Anovulatory bleeding is easy to treat with
low dose cyclic progestins Ovulatory bleeding can be difficult to treat
(high dose progestins) unless patients can take continuous OCPs or use Mirena
If acute, profuse bleeding, consider high dose progestin therapy
Conclusions
Most DUB can be medically managed- today we have more options
Endometrial ablation/resection offers an alternative to hysterectomy
Most endometrial cancer is preventable- must identify those at risk and TREAT!!! (biopsy first)