Dr Manal Behery Prof OB&GYNE ZAGAZIG UNIV 2014
Aug 17, 2014
Dr Manal Behery Prof OB&GYNE ZAGAZIG UNIV
2014
Source of androgens in women•
1-Ovarian theca and stromal cells <LH control
2-Adrenal cortex 3- Peripheral (< pre cursors)
Skin Adipose tissue Liver Placenta
Function of androgen in women ?
Estradiol production (aromatisation in granulosa cells <FSH control)
Sex drive
Muscular mass, etc…
The production rate of testosterone in the normal female is 0.2 to 0.3 mg/day
Normal total testosterone concentration in serum is below 0.8ng/ml
6
Androgen in circulation
7
Normal women Hirsute women
80% SHBG 79% SHBG
19% Albumin 19% Albumin
1% Free 2% Free
Types of hairLanugo
Fetal hair
VellusShort,fine, UnpigmentedBefore puberty
TerminalLong, coarse, pigmented arises from vellus hair
Androgen increase in the transformation of the vellus to terminal hair & increase sebaceous Follicle activity
Hirsutism:
Excessive growth of terminal hair in male sexual sites.
Hypertrichosis
Excessive growth of thin vellus hair at any body site
Drug-induced hypertrichosis
Causes
.
Hirsutism is a consequence of several factors
1.Androgen production
2. The sensitivity of the androgen receptors at the level of the hair follicle.
3.The activity of 5œ-reductase
Role of 5-Reductase
Converts Testosterone to Dihydrotestosterone in hair follicles
Is increased in both idiopathic and other forms of hirsutism
•the commonest cause (90%).• •More in African, Mediterranian population.
•Positive family history.•* No menstrual abnormalities.
* due to increased sensitivity of hair follicle
1) Constitutional (idiopathic):
(2) Ovarian cause:
1. PCO “→ the commonest cause.
2. . Stromal hyperthecosis.
3-Pregnancy luteoma
3. Androgen secreting tumors:
- Sertoli-lyedig tumors.- Gynandroblastoma.
Ovarian causes
Reproductive cycle regulated by HPO axis
LH, FSH androgen
Estrogen
GnRH
Anovulation
H-P-O axis Dysfunction in PCOS
(3) Adrenal cause:1.Congenital adrenal hyperplasia.
2. Cushing syndrome.
3. Androgen secreting tumors.
Congenital adrenal hyperplasia
4) Pituitary cause:
* Pituitary adenoma "Prolactinoma".
* Growth H. secreting tumor.acromegaly
Anabolic steroidsDanazolMetoclopramideMethyldopaPhenothiazinesProgestinsReserpineTestosterone
5) Iatrogenic:
(6) Obesity
hirsute alone
hirsute with pilosebaceous unit overactivity (acne)
hirsutism and ovulatory disorders
hirsutism and signs of virilization
Presentation of hirsutism
The clinical evaluation of hirsutism
When and where is the hair? Weight and menstrual history Family history Drugs Acne Symptoms or signs of virilisation
• Temporal hair loss• Voice change• Clitoral enlargement
Ferriman-Gallwey hirsutism scoring system
CLASSIFICATION
Hirsutism:Ferriman-Gallwey Scoring System
Acne: 50%Mild moderate severe
General examination.Thyroid disease,
Cushing syndrome,
Signs of virilization,
Signs of insulin resistance e.g. acanthosis nigricans.
Acanthosis Nigricans
• Velvety plaques on nape of neck and intertriginous areas
• Associated with insulin resistance
.Breast:
Galactorrhea
{Hyperprolactinaemia can be accompanied by increase in adrenal androgen}
Breast atropy
Pelvic exam for ovarian mass
Investigations
Investigations are needed if:
Hirsutism occurs in childhood
There are features of virilization Hirsutism is of sudden or recent onset
There is menstrual irregularity or cessation
Testosterone ng dl)
>200 <200
U/S of the ovary Anovulation
(PRL, TSH)
Adenxal mass Nothing
Laparotomy CT of the adrenala & ovaries
Laparotomy
Total Testosterone (T)DHEA-S (DS)17-hyroxyprogesterone (17-OHP)
T > 200 ng/dlDS > 700 μg/dl
Suspect Tumor
17-OHP > 2 ng/ml
Suspect CAH
T Elevated ±DS Elevated
DS Elevated
T & DS Normal PCOS
Adrenal
Idiopathic
Laboratory Evaluation
PCOS TLH/FSH
usually inc2/1
Late-onset CAH 17-OH-P >200 ng/dL
Androgen-secreting ov tumor Total T >200 ng/dL
Androgen-secreting ad tumor DHEAS >700 g/dL
Cushing syndrome Cortisol Increased
Exogenous androgen use Toxicology screen
Increased
TREATMENT
OCPs: first option when fertility is not desired
Decrease in LH secretion and decrease in androgen production
Increase in hepatic production of (SHBG) Decreased adrenal androgen secretion
Cyproterone acetate:
A progestin with strong antiandrogenic action.
Inhibits gonadotrophin secretion and compet efor androgen receptors on target organs
Dosage-
100mg from D5-D14 with ethinyloestradiol 30µg, from D 5 to D25
Androgen receptors blockade
Suppression of Androgen biosynthesis
Increased metabolic clearance of teststerone ( Testosterone Estrogen )
50-200 mg/day pd
Spironolactone + OC is well established regimen
Spironolactone, 50-200 mg per day
Insulin-Sensitizing Agents
Induction of ovulation
Some reduced hair growth
Improved glucose utilization
Lowered serum insulin
Lipid lowering properties
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FLUTAMIDE : Blocks the androgen receptors Decreases androgen production Usually used with OcsKETOCONAZOLE: Equally effective but danger of liver
toxicity Last resort of treatment.
Electrolysis:
.
Needle is inserted into the hair follicle
•a current is used to destroy the dermal papilla.
•All areas, usually the face
•May give permanent removal
•Pain, scarring, painful, repeat treatments needed, time consuming, expensive, pigmentation
b. Laser & intense pulsed light
• A light source sufficient to penetrate to the follicular bulge & the papillae is directed at the hair by probe.
•All areas
•May give permanent hair reduction, efficient, painless
•Dark hair required, expensive, scarring, skin pigmentation, repeated treatments usually necessary
Treatment options for hirsutism
Counselling Cosmesis Combined Oral Contraceptive Cyproterone acetate
• With or without COC e.g. Diane Spironolactone
• Causes irregular periods Topical Eflornithine
Questions?