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Fifth stage
Gynecology
Lec-
Dr.Asmaa
/ /2016
HIRSUTISM AND VIRILISM
The student at the end of this lecture should be able to :
Differentiate the hirsutism from virilisim.
Determine the severity by using ferriman gallway score.
Understand the sources of androgen in the body.
Classify the causes of hirsutism.
Analyze history and edxamination to predict the cause of hirsutism.
Outline the investigations required for diagnosis.
Describe the treatment of hirsutism case.
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Hirsutism : increase in terminal hair on the face ,chest ,back and inner thighs in a women
and the development of male escutcheon on the pubic hair(diamond , female is triangular).
It may be accompanied by anovulatory amenorrhoea,
dysfunctional uterine bleeding ,or infertility.
- Virilism : is development of hirsutism in addition to male features such as: Deepining of
the voice , frontal balding ,increased muscule mass , clitoromegaly , increased libido and
many features of defeminisation, such as decreased breast size and loss of vaginal
lubrication.
-Hisutism and virilism are both a clinical manifestation of androgen excess.
The defect is either:
Increase androgen production.
increase androgen transport
increase target organ response.
-The most common abnormality is increased androgen production which may arise from a
functional or neoplastic process.
Pathophysiology:
- the main source of androgen in women are the adrenal , ovary and peripheral
transformation in the liver and skin
-Androgen is synthesized from clolesterol together with estrogen ,progesterone.
-The stimulus for ovarian androgen production is pituitary LH ,for the adrenal is pituitary
ACTH.
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-The most commonly studied androgen which have biological significance are :
-Half of testosterone and androsteindione is produced by the ovary and other half from the
adrenal . DHEA ,DHEAS are mainly produced by the adrenal.
-99% of androgen are protein bound (inactive)1% is free (active).
-All preandrogen are converted in the liver to testosterone ,which is the main androgen.
In the peripheral tissue testosterone is converted to dihydrotestosterone (greater potency)
The pilosebaceous unit in the skin is sensitive to androgen stimulation ,so they are the
principalclinical sign of excess androgen production.
Causes of hirsutism:
Disorder of adrenal origin:
-cogenital or adult onset adrenal hyperplasia.
-androgen-producing tumors
Disorder of ovarian origin:
1-polycystic ovary syndrome
2-androgen producing tumor
*arrenoblastoma
*granulosa-theca cell tumor
* lutoma of pregnancy
3-hyperthecosis
4-chronic anovulation associated with:
*hypothalamic amenorrhea
*emotional disorders
*thyroid disorder
Disorder of pituitary origin:
-cushing’s syndrome
-acromegaly
Intersex problem:
-male pseudohermaphroditism
-Gonadal dysgenesis(turner’s syndrome)with androgen manifestation.
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Drug induced:
-Without virilization:phenytoin,diazoxide ,ACTH ,coticosteroids.
-With potential virilization:progesterone,anabolic agent,androgen therapy.
-Corticosteroid and androgen reduce SHBG so increase the free testosterone.
Intrinsic factors:
-genetic :racial, familial .
-Physiologic :premature pubarche ,precocious puberty,puberty,pregnancy and menopause.
-Idiopathic.
*Congenital adrenal hyperplasia:
21 hydroxylase deficiency :
-first most common.
- result in accumulation of 17-hydroxyprogesterone (normally not more than 200ng/dl ) .
-autosomal recessive
-newborn present with ambiguous genitalia life threatening salt-wasting.
-adolescent onset of severe hirsutism and virilism with menstrual irregularities.
11 B-hydroxylase deficiency result in accumulation of DHEA
*Cushing’s syndrome:
is the second major adrenal disease leading to excess cortisol and there is excess
production of androgen as intermediate product.
It’s due to pituitary adenoma , ectopic ACTH production or adrenal tumor.
It’s characterised by :
*Ovarian neoplasm:
-androgen secreting ovarian tumors are extremely
uncommon (functional tumor) or other like cystadenoma or krukenberg’s tumor (non
functional) will stimulate proiferation in adjecent ovarian stroma result in increase
androgen production.
-Arrenoblastoma or sertoli-leydig cell tumor usually give rise to a palpable mass.
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Evaluation of patient with hirsutism:
History :
onset: functional disorder as PCOS or late onset CAH often fiest appear at during
puberty and tends to progress slowely over several years .in contrast neoplastic
disorder can occurs at any time with sudden onset with rapid progression with
recent onset of virilization with some overlap in that 15% of patients with Hair in
syndrome can also exhibit asigns of virilization .
symptoms of hirsutism and virilism
menstrual history:regular(ideopathic)
drug history
family history
Examination:
Distribution of hair: ( modified Ferriman and Gallway score )severity and follow up
Body habitus and female contour
Breast examination for atrophic changes
Features of PCOS or cushing syndrome
Pelvic examination to exclude ovarian tumor
Diagnostic evaluation:
Laboratory evaluation:
1. free testosterone(androgen excess) level >200ng/dl suggest an adrenal neoplasm
2. 17 hydroxyprogesterone (CAH)and DHEAS(adrenal cause)
3. LH:FSH ratio >3 indicate PCOS
4. If normal testosterone 5 alpha reductase for peripheral conversion
5. pelvic ultrasound (ovarian tumor,PCOS)
6. CT scan or MRI (adrenal and ovarian tumor)
7. Dexamethasone suppression test if cushing syndrome is suspected(1mg ,8:00am
cortiol level should be less than 5 microg/dl) if positive high dose test should be
performed.
Treatment :
-treatment of the serious underlying cause as ovarian and adrenal tumors,hypophysectomy
for cushing syndrome, corticosteroid for virilizing adrenal hyperplasia.
-The largest group are of PCOS or idiopathic .
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-In idiopathic hirsutism medical treatment is used only after failure of cosmotic treatment.
-In PCOS or when there is associated problem of infertility or menstrual cycle irregularities
treat by induction of ovulation if the pregnancy is desired.
- Treatment require long time 6-9 month to notice the benefit Treatment require long time
6-9 month to notice the benefit so COCP is used together with other cosmotic treatment
till the response is established.
-Once the terminal hair is established treatment of the disease state will not remove the
total excess hair growth but will slow the rate of growth.
-Cosmotic treament are:
Temporary: Bleaching ,shaving, chemical and wax depilators .
Permanent: electrolysis, laser.
-Medical treatment :
A-Hormonal suppression:
1-combined oral contraceptive pills:
-decrease ovarian and adrenal production of steroids(androgen).
-progesterone suppress LH reduce ovarian androgen synthesis.
-Estrogen increase hepatic production of SHBG reduce free testosterone.
-estrogen decrease the conversion of testosterone to DHT in the skin by inhibiting the 5
alpha reductase.
2-Medroxyprogesterone.
3- GnRH analgs
4-Glucocorticoids: It’s used in a small dose of 0.25 mg to reduce the adrenal and ovarian
androgen it’s side effect are adrenal suppression and osteoporosis when used on long
term.
:
B-antiandrogen:
1-cyproterone acetate: is synthetic progesterone acts by inhibiting androgen binding to the
cytoplasmic receptors. It cause irregular bleeding so it should be combined with ethinyl
estradiol.
High Dose treatment( 100mg) for first 10 days of each cycle combined with ethinylestradiol
for 21 days , treatment required for 24- 36 months.
dianette is 30microgram ethinyl estradiol with 2mg cyproterone acetate
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2-spironolactone is adiuretic ,it’s an androgen blocker,it’s the most commonly used in
united state ,it competes with for testosterone binding sites,there by exerting a direct
antiandrogenic effects at the target organ,and it interfers with steroid enzymes and
decrease testosterone production. it’s also oppose the action of aldosterone so serum K
level should be monitered.
*Dose is 25-100 mg daily.
*both CPA and spironolactoe require contraception because the risk of feminization in
male fetuses if pregnancy occur
*Other antiandrogen like flutamide ,not used because their side effect(liver toxicity) with
action similar to spironolactone .
C-Steroidogenic enzyme inhibitor :
Ketoconazole :it can reduce androgen when given in a low dose of 200 mg/day.
D-5 alpha reductase inhibitor:
Finasteride:7.5 mg /day also femenise male fetuses so it’s used with COCP(contraception ).