Hirsutism is often a benign condition primarily of cosmetic concern. When hirsutism is accompanied by masculinizing signs or symptoms, particularly after puberty, it may be a manifestation of a more serious underlying disorder, such as an ovarian or adrenal neoplasm. Fortunately, such disorders are rare.

Hirsutism exceeding culturally normal levels can be as distressing an emotional problem as the loss of scalp hair.

The physiologic mechanism for androgenic activity consists of three stages: (1) production of androgens by the adrenals and ovaries, (2) androgen transport in the blood on carrier proteins (principally sex hormone-binding globulin [SHBG]), and (3) intracellular modification and binding to the androgen receptor.

Hirsutism can be caused by overproduction of androgens (from the ovaries or adrenal glands), increased peripheral conversion of androgen, decreased metabolism, and enhanced receptor binding (hair follicles that are more sensitive to normal androgen levels).

The amount of free testosterone and its byproduct dihydrotestosterone, is regulated by SHBG. Lower levels of SHBG increase the availability of free testosterone.

SHBG decreases in response to the following: exogenous androgens, certain disorders that affect androgen levels, such as polycystic ovary syndrome, congenital or delayed-onset adrenal hyperplasia, Cushing syndrome, obesity, hyperinsulinemia, hyperprolactinemia, excess growth hormone, hypothyroidism.

Conversely, SHBG increases with higher estrogen levels, such as those that occur during oral contraceptive therapy. The resulting increased SHBG levels lower the activity of circulating testosterone.

Increased circulating androgens result in an increased hair follicle size, hair fiber diameter, and duration of time hair follicles spend in the anagen (growth) phase. In addition to a change in hair quality and volume, oilier skin and hair may result from excess androgen.

For circulating testosterone to exert its stimulatory effects on the hair follicle, first it must be converted into its more potent follicle-active metabolite, dihydrotestosterone, by 5--reductase, an enzyme found in the hair follicle.

The severity of hirsutism does not correlate with the level of increased circulating androgens because of individual differences in conversion to 5--reductase and androgen sensitivity of hair follicles.

Increased androgens will result in hirsutism in androgen-sensitive regions of the body but leads to thinning of scalp hair.

Hirsutism presents with excess terminal hair in a masculine pattern. Sites include the face (particularly the moustache, beard, and temple areas), the chest, areolae, linea alba, upper back, lower back, buttocks, inner thighs, and external genitalia.

After familial and drug-induced causes for hirsutism have been excluded, hirsutism resulting from androgen excess should be considered.

Initial screening for total and free testosterone and DHEA-S often determines whether further testing is necessary.

Moderate elevations in DHEA-S suggest an adrenal origin of the hirsutism.

Normal levels of DHEA-S accompanied by high levels of testosterone indicate that the ovaries, and not the adrenals, are producing the excess androgen.

A tumor workup is indicated for total testosterone levels greater than 200 ng/dL (>100 ng/dL in postmenopausal women) or DHEA-S levels greater than 700 mcg/dL (400 mcg/dL in postmenopausal women).

In PCOS, the luteinizing hormone (LH) levels are elevated and follicle-stimulating hormone (FSH) levels are depressed, which results in elevated LH/FSH ratios (>2 is common).

If Cushing syndrome is suspected, a 24-hour urinary cortisol or an overnight dexamethasone suppression test should be performed.

Often appears during puberty as excess facial hair and prolongation of the preauricular hair line and is not associated with androgen excess.

Familial hirsutism is both typical and natural in certain populations, such as in some women of Mediterranean or Middle Eastern ancestry (Fig. 20.1).

Ovarian hirsutism leads to excess hair growth on the lateral face and around the areolae and is often accompanied by obesity, severe acne, and seborrheic dermatitis.

Polycystic ovary syndrome (PCOS) is the most common cause of androgen excess-related hirsutism.

• In PCOS, virilization is minimal and hirsutism is often prominent.

• Characteristic features include menstrual irregularities, dysmenorrhea, occasional glucose intolerance and hyperinsulinemia, and, often, obesity.

• The hyperinsulinemia is believed to hyperstimulate the ovaries into producing excess androgens.

• Women with PCOS may show other cutaneous manifestations of androgen excess in addition to hirsutism, such as recalcitrant acne (Fig. 20.2), acanthosis nigricans, and alopecia on the crown area of the scalp (a pattern that contrasts with the bitemporal and vertex androgenic alopecia seen in men).

Other ovarian causes are usually associated with virilization and include luteoma of pregnancy, arrhenoblastomas, Leydig cell tumors, hilar cell tumors, theca cell tumors.

Excess growth of facial hair is seen in elderly postmenopausal women and may be caused by unopposed androgen that occurs after menopause.

Adrenal hirsutism results in excess hair in a “central” distribution on the anterior neck, abdomen, and suprapubic area.

Children with congenital adrenal hyperplasia (CAH), the classic form of adrenal hyperplasia, may exhibit hirsutism. Such children may be born with ambiguous genitalia and symptoms of salt wasting, failure to thrive, and develop masculine features.

Late-onset congenital adrenal hyperplasia affects about 1% to 5% of hyperandrogenic women. Although these patients have clinical features that resemble PCOS, they manifest no salt-wasting symptoms and may not develop signs of virilization or menstrual irregularities until puberty or adulthood (Fig. 20.3).

Cushing syndrome is a noncongenital form of adrenal hyperplasia. It is characterized by an excess of adrenal cortisol production. The excessive growth is predominantly vellus (nonandrogen-dependent) hair.

Androgen-producing adrenal tumors are extremely rare. Hirsutism appears rather abruptly when an androgen-secreting tumor arises.

Hyperprolactinemic hirsutism results in excess growth both centrally and laterally and is sometimes accompanied by seborrhea, acne, oligomenorrhea, and galactorrhea.

Drugs that can induce hirsutism by their inherent androgenic effects include dehydroepiandrosterone sulfate (DHEA-S), testosterone, danazol, and anabolic steroids.

The current low-dose oral contraceptives are less likely to cause hirsutism than were previous formulations.

The few hirsute women who do not have a familial form of hirsutism or any detectable hormonal abnormality are usually given a diagnosis of idiopathic, or end-organ, hirsutism.

Such patients have normal menses, normal-sized ovaries, no evidence of adrenal or ovarian tumors or dysfunction, and no significant elevations of plasma testosterone or androstenedione.

Antiandrogen therapy may improve hirsutism in some idiopathic cases which suggests that this form of hirsutism may be androgen induced.

It is believed that many of these women may have mild or early PCOS and androgen levels in the upper normal ranges.

Other less common but potentially serious disorders associated with hirsutism include anorexia nervosa, acromegaly, hypothyroidism, porphyria, and certain cancers.