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:

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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?