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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 hirsutism, virilization, hersutism, hirsute, excessive hair 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, virilization, hersutism, hirsute, excessive hair

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 in

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, but the adrenal is the

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, and 

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, the

TABLE 15-13 -- Classification of Hirsutism and Virilization
    Sex cord tumors
    Germ cell tumors
    Hilar cell tumors
    Adrenal rest tumors
    Mixed germ cell and gonadal tumors
    Tumors with functioning stroma
  Pregnancy associated
    Hyperreactio luteinalis
  Congenital adrenal hyperplasia/adult-onset adrenal hyperplasia
    21-Hydroxylase deficiency
    11beta-Hydroxylase deficiency
    3beta-Hydroxysteroid dehydrogenase deficiency
  Cushing's syndrome
  Anabolic steroids
  Progestagens (19-norsteroid derivatives)
  Acromegaly Menopause

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. Menopausal

TABLE 15-15 -- Clinical Features of Hormone-Producing Ovarian Tumors

Age in Years Incidence of

Tumor Hormones Produced Peak Range Malignancy
(% )
(% )
Size in cm Miscellaneous
Sex cord-stromal tumors

  Granulosa-theca cell tumors Estrogen, androgens, progestagens 30-70 <1-92   10-20 10-15 <1->30 Most common functioning ovarian neoplasms
  Androblastomas (Sertoli-Leydig cell tumors) Androgens, estrogens 20-40 4-84   20 Rare <5->25 Most common virilizing tumors
Lipid cell tumors

  Hilar cell type Androgens 45-75 4-86   Rare Rare 0.5-15 --
  Adrenal cell type Estrogens 20-25 6-78   20 Rare 0.5-30 Often associated with diabetes
Germ cell tumors

  Dysgerminomas Chorionic gonadotropin 10-30 4-76   100 5-10 3-50 --

    Carcinoids Serotonin 50-70 36-79   Rare Rare <1-15 Carcinoid syndrome may occur
    Stuma ovarii Thyroxine 30-60 21-69   Rare   Rare <5-20
    Mixed carcinoid and struma Serotonin, thyroxine 40-60 21-77   Rare   None <1-26 May be clinically hyperthyroid (rare)

  Choriocarcinomas Chorionic gonadotropin 6-15 6-42   100 Rare >5 --
Gonadoblastomas Androgens, chorionic gonadotropin 10-30 6-36   50   40 <1->30 Usually occur in male pseudohermaphrodites

women also often complain of increased facial hirsutism, but this is physiological because of the change in the ratio of estrogens and androgens.

The diagnosis and evaluation of hirsutism require a careful history and physical examination as well as laboratory testing. Familial occurrence, age at onset, severity, and rate of progression are important. Hirsutism that begins at the expected time of puberty may be

The treatment of hirsutism is not ideal, in that cures are rarely possible. The therapeutic approach is directed first at decreasing the rate of androgen secretion or inhibiting androgen action in the pilosebaceous unit itself. Oral contraceptives are commonly used to treat ovarian causes of hirsutism. Other drugs that may be useful include LHRH analogues, antiandrogens (e.g., spironolactone), and

After androgen secretion or androgen action is reduced, additional physical methods to remove hair may be instituted. These include

Surgical removal of the ovaries may be indicated in women with hyperthecosis in whom childbearing is no longer desired and in whom

Drugs to Treat Hirsutism

Because abnormal hair growth can be caused either by excess androgen secretion or by increased sensitivity to androgens, treatment is

Oral Contraceptives

The most commonly used therapy for hirsutism is the oral contraceptive pill. Oral contraceptives lower androgen levels primarily by


The most widely used antiandrogens for the treatment of hirsutism are spironolactone (100 to 200 mg/d by mouth) and cyproterone acetate (50 to 100 mg/d by mouth). Both act primarily to block androgen effects at the pilosebaceous unit by competing with testosterone for the androgen receptor. Cyproterone acetate also inhibits LH levels, whereas spironolactone inhibits CYP enzymes


Two glucocorticoids, dexamethasone (0.25 to 0.5 mg) and prednisone (2.5 mg), have been used for treatment of hirsutism of adrenal

Other Treatments

LHRH analogues are potentially useful for treatment of hirsutism. Nasal, subcutaneous, and depot forms are available (see later discussion). Ketoconazole, an imidazole derivative, inhibits production of CYP-linked steroidogenic enzymes (principally

LHRH Analogues

Inhibition of gonadotropin release to the point of hypogonadism may be produced by LHRH agonists or antagonists. The agonist gonadorelin requires continuous infusion, whereas long-acting agonists such as leuprolide acetate or antagonists can be given once daily.