HIRSUTISMJeetendra Bhandari

Patan Academy of Health Science-School of Medicine5th year Medical Student

Introduction• Hirsutism is excessive growth of androgen dependent sexual

hair(terminal hair) in central part of body

Some common term• Virilism

Presence of any one or more of the following feature• Deepening of voice• Temporal balding• Amenorrhea• Enlargement of clitoris(clitoromegaly)• Breast atrophy

• HyperandrandrogenismState of increased serum androgen level with or without any biological effect of hyperandrogenemia

• Hypertrichosisexcessive hair growth limited to a normal pattern of distribution

Androgen in female • Dehydroepiandrosterone sulphate(DHEA-S)• Dehydroepiandrosterone (DHEA)• Androstenedione• Testosterone(T)• Dihydrotestosterone(DHT)

Source of androgen in female

• Most if Testosterone(80%) in circulation is bound to SHBG and is biologically inactive• About 19% is bound loosely with albumin• 1% of testosterone remains free which is biologically active• Biological effect of testosterone is metabolically converted in tissue to

dihydrotestosterone(DHT) by enzyme 5ἀ-reductase• 3 ἀ-androstanediol glucuronide (3 ἀ-AG) is tissue metabolite of DHT• 3 ἀ-AG reflects activity od enzyme 5 ἀ reductase at tissue level

• Biochemical marker for androgen compartment • Testestorone for overies• DHEA-S for adrenal gland• 3 ἀ-AG for periphery

Biology of Hair growth• Hair grows (at 8-10 weeks of gestation) from a individual hair follicle

that are part of a pilosebaceous gland apparatus• Main difference between sexes is the degree of differentiation of the

hair• Human hair growth is continuous• Hair grows in a mosaic pattern (in a given area ,hair are in different

stages of development)

Growth cycle of the Hair: ACT• Anagen : Growth phase,85- 90 % of the life cycle• Catagen : rapid involution Phase• Telogen : Quiescent phase

The growth phase or the anagen phase is primarily influenced by disorders that stimulate hair growth as well as therapeutic modalities

Types of hair• Lanugo : Body hair seen in the fetus and newborn• Vellus : Fine (downy unpigmented) hair covering the body• Terminal hair : Thick pigmented hair of scalp and pubic area

Thickness of the terminal hair varies form one individual to other depending upon genetic, and possibly nutritional

Androgen and Pilosebaceous unit• Pilosebaceous unit consists sebaceous gland and hair follicle• Both are sensitive to androgen• Sebaceous glands are more sensitive to androgen than hair follicle• Hyperstimulation of sebaceous gland lead first to oily skin and

subsequent infection result in acne• Skin and hair follicle also play role in serving as target organs of

androgen and also in producing androgen from circulatory prophormones

Mechanism of excessive hair growth• Stimulus for excessive hair growth is testestrone• Testestrone binds to androgen receptor in hair follicle activation of

5ἀ-reductase convert testosterone to dihydrotestestrone and androstenediol• This lead to stimulation of proliferation and growth of terminal

hair(anagen Phase)• Once blace terminal hair is produced, changes persists in absence of

continuing androgen excess

• Increased hair follicle stimulation and increased 5ἀ-reductase activity enable prohormone DHEA and androstenedione to be metabolized directly to DHT

Pathophysiology• Increased concentration of serum androgens especially of testosterone.• Decreased level of SHBG resulting in increased free testosterone

(testosterone itself reduces SHBG level)• Increased responsiveness of the target organ (skin) to the normal

circulating androgens• Increased activity of 5α-reductase which converts testosterone to DHT in

the skin and hair follicles

TtestestoroneSHBG Sex Hormone Binding GlobulinDHT Dihydrotestestrone

Causes • Ovaries• Polycystic ovarian syndrome(PCOS)• Sertoli-Leydig cell tumor• Hilus cell tumor• Hyperthecosis- Luteoma of pregnancy

• Adrenal• Adrenal hyperplasia• Cushing’s syndrome• Adrenal tumors

• Obesity• Obesity increase insulin abnormal glucose tolerance/diabetes mellitus increase

androgen production decreased SHBG increased free testestrone and E2

• Exogenous(drug therapy)• Androgens• Anabolics• OCP• Synthetic progestogens

• Postmenopausal• Pituitory tumor• Idiopathic

Investigations

Management principle• To remove source of excess androgen• To supress or neutralize action of androgen• Remove excess hair

Reduce source of excess androgen• Weight reduction• Surgically treatment of adrenal or ovarian tumor• Cushing’s disease can be treated by adrenalectomy• In iatrogenic cases, offending drugs should be stopped

Supress action of androgen• Combined steroidal contraceptive pill• Dexamethasone• Antiandrogens

Contraceptive pill• Mode of action• Suppression of LH secretion from the pituitary• Anti-androgen at level of hair follicle• Elevation of SHBG(estrogen effect)• Progestins in OC pills inhibits 5ἀ-reductase activity in skin• Inhibits adrenal androgen secretion

• Case selection• Suitable in case of PCOS or idiopathic group in young and unmarried where

only T is elevated

• Dexamethasone• Acts by suppressing pituitary-adrenal axis• Used in adrenal or mixed adrenal and overian hyperandrogenism• Dose0.25-1 mg daily at bed time

• GnRH agonists• Used to supress selectively ovarian steroid production by inhibiting LH

secretion from pituitary• Used only when other anti-androgen have failed to give response

Anti-Androgen• Cyproterone acetate(derivative of 17-OHP)• Inhibit gonadotropin secretion; interfere with androgen action on target

organ by competing for androgen receptor• Blocks action od DHT and T at both nucleus and cytosol receptor level• Should be administerd along with ethinylestradiol to prevent menstrual

irregularities and ovulation• Available as combined estrogen-progestin OCP• Improvement of hirsutism seen after 3 months of therapy• Side effect: nausea, fatigue, weight gain, loss of libido and mastalgia

• Spironolactone• Is an aldosterone antagonist and acts as a potassium sparing diuretics• Inhibits ovarian and adrenal androgen biosynthesis• Competes with DHT for androgen receptors in hair follicle • Inhibits 5ἀ-reductase activity directly• 100-200 mg ; orally ; daily; maintainance dose-25-50 mg daily• Side effects

• Menstrual irregularity• Fatigue• Hyperkalamia

• Flutamide• Nonsteroidal anti-androgen• Blocks androgen receptor as well as it inhibit testestrone biosynthesis• Results observed after 3 months of therapy• Given dose 100-200 mg daily• Side effect:

• Nausea• Dry skin• Headache• Hepatotoxicity

• Finasteride• Inhibit 5ἀ-reductase activity• Improves hirsutism significantly without any side effect• Daily dose 5 mg

• Ketoconazole• androgen receptor antagonist• inhibits androgen biosynthesis from ovary and adrenal• Inhibits 5α-reductase activity• competes with androgen at the receptor sites• dose varies from 25–150 mg per day• Side effects: Menstrual irregularity, fatigue, diuresis and electrolyte

imbalance(hyperkalemia).

• Insulin sensitizing drugs• Treated in PCOS• Treated with metformin and thiazolidineases• Decrease circulating insulin and androgen levels

• Glucocorticoides• Used to supress endogenous ACTH secretion • Less effective

Duration of therapy• Response of all drug are slow• Drug should be continued for at least 6 months• Anti androgen inhibit the growth of new hair follicle but fails to

remove hair that is already present

Removal of hair• Excess hair removed by bleaching, twitching, epilation, waxing, lasers,

shaving or electrolysis• Laser and pulse light therapy destroy hair follicle• Skin pigmentation may occur• In electrolysis, individual hair follicle is destroyed• Side effects: Pain, scarring and pigmentation

References• DC Datta. Hirsutism. 6th ed. 2014. P:571-6.• Polycystic overian syndrome and hyperandrogenism. Willim’s

Gynaecology. 2nd ed.P:460-5.• http://www.skincarencure.info/wp-content/uploads/2014/11/hirs1.gif• http://skincarebylouisa.com/wp-content/gallery/hirsutism/graphic-4-

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