HIRSUTISM - Excessive Growth Of Androgen Dependent Sexual Hair

Hirsutism is the excessive growth of androgen dependent sexual hair (terminal hair) in facial and

central part of the body that worries the patient.

Hypertrichosis: Hypertrichosis connotes excessive growth of non-sexual (fetal lanugo type) hair.

Hyperandrogenism: Hyperandrogenism is a state of increased serum androgen level with or without any biological effect of hyperandrogenemia.

Virilism: Virilism is defined as the presence of any one or more of the following features—deepening of the voice, temporal balding, amenorrhea, enlargement of clitoris (clitoromegaly) and breast atrophy. It is a more severe form of androgen excess. Virilism may be due to adrenal hyperplasia or tumors of adrenal or ovary.

In female major androgens are: dehydroepiandrosterone sulphate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, testosterone (T) and dihydrotestosterone (DHT). All androgenic activities are due to T and DHT.

Testosterone is the second most potent androgen in circulation, the first one being dihydrotestosterone normal female is 0.2–0.3 mg. Approximately, 50 percent of testosterone arises from peripheral conversion of prohormones, predominantly androstenedione. The principal sites of peripheral conversion are skin, muscle, fat, liver and lungs. The adrenal glands (z. reticularis and z. fasciculata) and ovaries (theca, stroma and granulosa) contribute approximately equal amounts (25%) to the circulatory levels of testosterone. Dehydroepiandrosterone sulphate (DHEA-S) arises exclusively from the adrenal glands while about 50 percent of DHEA is secreted from the adrenals.

Androstenedione arises from the adrenals and ovaries in equal amount. The sources of androgens in normal female are schematically depicted below. Most of testosterone (80%) in the circulation is bound to SHBG and is biologically inactive. About 19 percent is bound loosely with albumin and only 1 percent of the testosterone remains free which is biologically active. Normally total circulating testosterone level is 20–80 ng/dl. To exert a biological effect, testosterone (T) is metabolically converted in target tissues to dihydrotestosterone (DHT) by the enzyme 5α-reductase. DHT is the most potent androgen to stimulate the hair follicles and sebaceous glands (pilosebaceous unit). 3α-androstanediol glucuronide (3α-AG) is an important tissue metabolite of DHT. 3α-AG is thought to reflect the activity of the enzyme 5α-reductase at tissue level. T → (5α-reductase) → DHT → 3α-androstanediol (3α-A) → 3α-androstanediol glucuronide (3α-AG). Therefore, the biochemical marker for each androgen compartment is different. For the ovary it is testosterone; for the adrenal gland it is DHEA–S and for the periphery it is 3α–AG.

The pilosebaceous unit consists of sebaceous glands and hair follicles. Both are sensitive to androgens. The sebaceous glands are more sensitive to androgens than the hair follicles. Hyperstimulation of the sebaceous glands leads first to oily skin and subsequent infection results in acne. The skin and hair follicle play an active role in serving as target organs for the androgens and also in producing androgens from circulatory prohormones.

The stimulus for the excessive hair growth is testosterone. Testosterone binds to the androgen receptors in the hair follicle. This is followed by activation of the enzyme 5α-reductase. This will convert testosterone to most potent androgen—dihydrotestosterone (DHT) and androstenediol which stimulate proliferation and growth of terminal hair (anagen phase). Once the black terminal hair is produced,