HIRSUTISM AND VIRILISM

Dr.Amina Zakaria Al-tutunji

M.B.Ch.B, MD.
Obstetrics and Gynecology
College of medicine/University of Mosul

HIRSUTISM AND VIRILISM

Definition
* Hirsutism is excessive growth of terminal (coarse) hair on the face, chest, back or inner thighs in women following a male like pattern.See fig.1
* Virilization refers to concurrent presentation of hirsutism with a broad range of signs suggestive of androgen excess, such as
-Acne
-Frontotemporal baldind
-Deepening of the voice
-A decrease in breast size
-Clitoral hypertrophy
-Increase muscle mass
-Amenorrhoea/ oligomenorrhoea

Epidemiology

Hirsutism affect between 5% & 15% of women.
Fig.1 hirsutism
Pathophysiology
The main source of androgen in women are the adrenal, ovary & peripheral transformation in the liver & skin.Androgen is synthesized from cholesterol .The stimulus for ovarian androgen production is pitutary LH & for the adrenal is pitutary ACTH.
All preandrogen (androstendione, DHEA , DHEAS )are converted in the liver to testosterone; which is the main androgen.
In the peripheral tissue and by the action of 5a-reductase (5a-RA) found in hair follicles and sebaceous glands, converts testosterone to dihydrotestosterone (DHT), the most biologically active androgen. See fig.2
Most circulating androgens are bound to SHBG (inactive). Only 1% of androgen circulate freely (active).

Both hirsutism and virilism are a clinical manifestation of androgen excess, the defect is either in;
* Increase androgen production
*Increase androgen transport.
*Increase target organ response.


Causes of hirsutism
1-Disorder of adrenal origin
-congenital or adult onset adrenal hyperplasia.
-adrenal-producing tumors
2-Disorder of ovarian origin
-PCOS (90%)
-androgen producing tumor
arrenoblastoma
Granulosa-theca cell tumor
-Chronic anovulation associated with
Hypothalamic amenorrhoea
Emotional disorders
Thyroid disorder
3-Disorder of pitutary origin
Cushing's syndrom
Acromegaly
4-Drug-induced Fig.2 androgen production
Phenytoin, diazoxide, danazole, corticosteroids, androgen therapy and others
5-Intrinsic factors
Genetic; racial, familial
Idiopathic
6-Intersex problem
Gonadal dysgenesis (turner's sgndrom) with androgen manifestation.


The Ferriman-Gallwey score
*Is a method of evaluation and quantifying hirsutism in women
*Hair growth is rated from 0 (no growth) to 4 (complete and heavy cover), in 9 locations (upper lip, chin, chest, upper back, lower back, upper abdomen, lower abdomen, the upper arm and thigh), giving a maximum score of 36.
In white races, a score of 8 and above is considered indicative of androgen excess. Fig.3

Fig.3

Ferriman-Gallwey score

Clinical evaluation

History
*Onset & duration: sudden (neoplastic), gradual (PCOS)
*Symptoms of hirsutism and virilism
*Menstrual history
*Family history
*Drug history

Examination

---General
Distribution of hair using Ferriman-Gallwey score
Features of PCOS
Thyroid disease
Cushing syndrom
Sign of virilization
Sign of insulin resistance eg. acanthosis nigricans.
---Breast
Galactorrhea (hyperprolactinaemia can be accompanied by increase in adrenal androgen)
---Pelvic
Mass.


Investigations
1-Free testosterone level >200ng/dl suggest an adrenal neoplasm..
2-17 hydroxyprogesterone ......CAH.
3-LH:FSH ratio > 3....indicate PCOS.
4-(5a RA), if testosterone level is normal.
5-Pelvic U/S......ovarian tumor or PCOS.
6-CT scan or MRI
7-Dexamethasone suppression test........if Cushing's syndrom suspscted.
8-Thyroid function test

Treatment

1-General
2-Specific
3-Local
4-Surgery

1-GENERAL

*Reassurance, explain the condition, treatment regimen & the time required.
*Stop smoking
*Weight reduction


2-SPECIFIC
*Ovarian suppression
OCP
Progestagen
GnRha
*Adrenal suppression
Corticosteroids
*Anti-androgens
Spironolactone
Cyproterone acetate
Flutamide
Ketoconazole
*5aRA inhibitors
Finasteride
*Insuline sensitizer
Metformine.

Oral contraceptive pills

COCP, and in particular one containing the anti-androgen Cyproterone acetate are the most popular treatment for hirsutism. The new pill Yasmin is also helpful.
The mechanism of action : the estrogen in the COCP;
---increase the estrogen level in the blood_______ reduce hirsutism
---increase the SHBG _______decrease the amount of free androgen
---suppress gonadotrophin (FSH & LH)______ lower the level of ovarian androgen production.
---inhibiting 5aRA____decrease conversion of testosterone to DHT in the skin.


Cyproterone acetate
Is synthetic progesterone act by inhibiting androgen binding to the receptors.
Dose.....50-100 mg from D5-D15
Side effect; menstrual irrigularities, mastalgia, feminization of male fetus, loss of libido, fatigue, oedema, wt.gain & glucose intolerence.
Treatment required for 24-36 months
Dianette is 30 microgram ethinyl estradiol with 2 mg Cyproterone acetate

Spironolactone

Is a diuretic, it inhibit androgen synthesis and has antiandrogen action in target cell.
Dose....25-100 mg daily.
Both Cyproterone acetate and Spironolactone require contraception because the risk of feminization in male fetus if pregnancy occur.

Ketoconazole

It can reduce androgen when given in a low dose of 200 mg/ day.

Finasteride

Dose .....7.5 mg/ day, also feminise male fetuse so its used with COCP.

3-LOCAL

Suppress hair growth: Eflornithine Hydrochloride (Vaniqa)
Remove hair pigment: Bleaching
Temporary depilation: shaving.
Temporary epilation: waxing.
Perminant removal: Electrolysis, laser


4-SURGERY
Guide lines for management
1-The most desirable & effective treatment is combination of OCP & antiandrogen.
2-Response is relatively slow & at least 6 months are required to demonstrate an improvement.
3-Treatment should continued for at least 1-2 yr.
4-There is no evidence that one agent is better than another & choice should be governed by cost & side effect.
5-The addition of GnRHa should be reserved for patient resistant to initial treatment.

GOOD LUCK

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