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Hirsutism and Virilization

Hirsutism is defined as the presence of excessive growth of hair in locations where hair growth in women is normally minimal or absent. Although it may be the initial sign of a serious underlying disorder, hirsutism by itself is usually benign and is frequently associated with PCOS. In contrast, virilization is the combination of hirsutism plus other signs of masculinization, such as clitorimegaly, deepening of the voice, temporal balding, decreased breast size, and loss of female body habitus. Virilization is less common than hirsutism and is more often associated with a potentially serious disorder such as an ovarian or adrenal tumor. Hirsutism is usually associated with normal or slightly elevated levels of serum androgens, whereas virilization is associated with markedly increased androgen production by the ovary or adrenal (or both) and hirsutism.

The number of hairs per unit area of skin is determined by genetic factors and is the same for both sexes of a similar ethnic background. For example, women and men of Mediterranean descent tend to have more body hairs per unit area than do Asians. In both women and men, hair follicles cover the body except for the lips, palms of the hands, and soles of the feet. Hair follicles are of two types: vellus and terminal.  In women, excess androgen production stimulates vellus hairs to develop into long, coarse, pigmented terminal hairs in most areas of the body except the scalp, where terminal hairs are converted to vellus hairs, eventually resulting in temporal balding. Androgens stimulate, whereas estrogens inhibit hair growth.

The primary mechanism leading to the development of hirsutism and virilization is increased secretion of androgens by the ovary or adrenal. Under normal circumstances the circulating testosterone level is derived from direct secretion by the ovary and by extraglandular conversion of androstenedione secreted by the ovary and the adrenal. Little, if any, testosterone is released by the adrenal.

In women with isolated hirsutism, 75% of circulating testosterone is from ovarian secretion. In the presence of increased levels of testosterone, TeBG levels are reduced, leading to increased free testosterone and an increased metabolic clearance rate for testosterone. In women with mild hirsutism who have ovulatory menstrual cycles and normal levels of testosterone, androstenedione.

A frequent cause is ovarian dysfunction, and in this category the most common cause is PCOS. As discussed earlier, PCOS is diagnosed on clinical grounds, and the onset of hirsutism and other symptoms associated with the syndrome usually occurs at about the time of menarche. In most cases, the rate of progression of hirsutism is constant but slow. On rare occasion signs of virilization (e.g., clitorimegaly) may develop in women with PCOS; this usually occurs as a result of particularly high rates of testosterone secretion in women with stromal hyperthecosis, a condition in which islands of luteinized thecal cells are present in the ovarian stroma distant from ovarian follicles. Hyperthecosis is probably not a distinct entity but rather an exaggerated manifestation of PCOS. Women with 

The association of hyperandrogenism, insulin resistance, and acanthosis nigricans (so-called HAIR-AN syndrome) constitutes a specific subset of PCOS or hyperthecosis.   In women with type A insulin resistance resulting from intrinsic defects in the insulin receptor.

Ovarian tumors may secrete a variety of hormones in addition to androgens, including estrogens, hCG, serotonin, and thyroxine. All choriocarcinomas, some dysgerminomas, and a few malignant ovarian teratomas secrete hCG. Primary ovarian carcinoids may produce

Adrenal virilization is most commonly caused by congenital adrenal hyperplasia (21-hydroxylase deficiency). In women the diagnosis is usually made at birth because of sexual ambiguity.  Less severe forms are caused by mutations that impair the function of the gene less

Iatrogenic hirsutism may result from drug therapy. One cause of hirsutism, amenorrhea, and signs of virilization is the use of androgens for the purpose of body-building or in treatment of diminished libido or menopause. Other drugs that cause hirsutism include danazol, metyrapone, phenothiazines, phenytoin, diazoxide, and minoxidil.