DEFINITION

Hirsutism is defined as a male pattern of hair distribution in a female, with the hair being transformed from fine villous hair to visible, coarse, terminally medullated hair under the influence of androgens.¹ Hirsutism must be distinguished from hypertrichosis and lanugo. Hypertrichosis is the growth of villous hair that is not androgen dependent and that is prominent in sexual and nonsexual areas. Lanugo is very soft, villous, nonpigmented hair that covers the body.

EPIDEMIOLOGY

Overall, the prevalence of hirsutism is unknown but may be as high as 50%. It is said that “even a single hair casts a shadow,” so that in cultures in which a lack of hair is a feature of female beauty, minimal hirsutism is considered a disorder, whereas in other cultures, in which some excess hair growth is acceptable, a significant change in the pattern and texture of the hair needs to be present before it is deemed a problem. In a classic British study of 430 normal women, there was no hair seen on the upper back or abdomen, indicating that the presence of hair in these areas is abnormal. In this study, 10% had hair on the chest, 22% had chin hair, and 49% had hair on the upper lip. The distribution of hair was very scanty in all these areas. Hence, the ethnic background, as well as distribution and density of hair growth, determine the degree of hirsutism. The practicing physician must place the patient in the spectrum of individuals in the locality in which he or she practices to be able to assess the severity of hirsutism objectively. In addition, the age at onset, rate of growth and progression, and associated symptoms and signs can determine the severity of the problem.

ETIOLOGY AND PATHOGENESIS

Androgens are a prerequisite for sexual hair development. Hirsutism can arise from increased androgen production or from increased sensitivity of the hair follicles to circulating androgens.

Testosterone is the most important circulating androgen because of its relatively high plasma concentration and greater potency at the target organ level. Circulating testosterone is the sum of the secretion from the ovaries (35%-40%) and adrenals (40%) in response to the tropic hormones—luteinizing hormone (LH) and adrenocorticotropic hormone (ACTH)—respectively. The remaining circulating testosterone is derived from the conversion of androgenic precursors, mainly androstenedione (derived from the ovaries and adrenals) and dehydroepiandrosterone (DHEA; derived almost exclusively from the adrenals).^1–3 Peripheral conversion of androgenic prohormones to testosterone occurs in the liver, skin, and adipose tissue.^1–3 Testosterone is present in the circulation as the free or conjugated form. Almost 98% to 99% of plasma testosterone is bound to steroid hormone-binding globulin (SHBG), to cortisol-binding globulin, or nonspecifically to albumin and other proteins and is biologically inactive. The free portion of testosterone is biologically active. In the hair follicles, testosterone is converted to its biologically active form, dihydrotestosterone, by the enzyme 5α-reductase.^1–3

Sex hormones work independently in the liver to control SHBG production. Estrogens increase and androgens decrease the production of SHBG. Thus, in hyperandrogenic states, the SHBG level is decreased, thereby allowing even higher free androgen levels. The other major modulator of SHBG is insulin. Insulin decreases the production of SHBG so that in conditions of insulin resistance and compensatory hyperinsulinemia, the SHBG level is decreased.

SIGNS AND SYMPTOMS

History should include age at onset, rate of progression, virilization, family history, and current medications. Idiopathic hirsutism typically begins at the peripubertal age. Rate of progression is important because hirsutism caused by malignant lesions progresses rapidly. The presence of virilizing signs such as change in voice, male-pattern baldness, clitoromegaly, change in muscle distribution, and increase in libido make the presence of a serious underlying disorder likely. Family history, race, and ethnicity are important determinants of hirsutism; patients of Mediterranean, Middle Eastern, or South Asian descent are more likely to be hirsute without necessarily having significantly elevated androgen levels. Finally, current medications should be evaluated to screen for the use of androgenic steroids.

The amount and distribution of hair are an index of androgen effect. As noted, before puberty, most of the body is covered by fine, nonpigmented, nonmedullated hair called villous hair. In the presence of androgens, these hairs are converted to coarse, pigmented, medullated terminal hairs. Terminal hair on the face, around the areola, and on the abdomen below the level of the umbilicus is present in 10% of “normal” women. Terminal hairs of the upper back, shoulders, sternum, and upper abdomen suggest a more marked androgen effect.

Grading of hirsutism is done using the Ferriman-Gallway scale, which semiquantitatively measures the amount of hair growth; however, it is subject to large observer variability. Examination should include a search for signs of virilization such as male-pattern baldness, decreased voice pitch, increases muscle bulk, and clitoromegaly (length >10 mm or clitoral index [length × width] >35 mm²). Signs of insulin resistance (e.g., acanthosis nigricans, abdominal obesity), Cushing’s syndrome, and ovarian enlargement should be sought during the examination.

DIAGNOSIS

The goals of biochemical assessment are to evaluate the source of hyperandrogenism and to rule out the presence of a malignancy. Some physicians recommend no further evaluation in patients with mild hirsutism and regular ovulatory menses because these women do not have a serious underlying disorder.¹ The major biochemical parameters tested are discussed next.

Testosterone, total and free, should be measured. In most patients with hirsutism, especially that associated with abnormal periods, the testosterone levels are high-normal or just above the upper limit of normal. The free testosterone level is also similarly affected. Values of total testosterone higher than 200 ng/mL suggest an androgen-producing tumor. Because testosterone has a diurnal rhythm and varies with the menstrual cycle, most norms are standardized to early morning blood samples drawn between days 4 and 10 of the cycle. In the absence of cycles, a random early-morning sample usually suffices.

DHEAS should be measured, but marginal elevations of the DHEAS level are common. Elevated values suggest an adrenal source of androgens. Levels higher than 700 µg/dL suggest an androgen-producing adrenal tumor. These patients should undergo further evaluation with computed tomography or magnetic resonance imaging to check for a tumor.

17-Hydroxyprogesterone, a precursor of cortisol, should be measured. To screen for adult-onset CAH, it should be measured between 7 AM and 9 AM in the early follicular phase of the menstrual cycle. Levels lower than 200 ng/dL exclude the disease. Mildly increased levels, from 300 to 1000 ng/dL, require an ACTH stimulation test. Cosyntropin (synthetic ACTH), 250 µg, is administered intravenously, and levels of 17-hydroxyprogesterone are measured before and 1 hour after the injection. Poststimulation values that exceed 1000 ng/dL indicate a positive test result.

Free cortisol in a 24-hour urine sample should be measured in women with signs and symptoms of Cushing’s syndrome.

Prolactin levels should be measured because an occasional woman with hirsutism and irregular menses could have hyperprolactinemia caused by hypothalamic disease or a pituitary tumor. Levels are also mildly elevated in up to 20% of patients with PCOS.

Serum follicle-stimulating hormone (FSH) level should be measured if ovarian failure is a consideration, but otherwise it is of minimal help.

Serum LH level should be measured because women with PCOS tend to have higher serum LH levels and a ratio of LH to FSH levels higher than 3. This is believed to be significant by some, but most authorities do not consider this a requirement for the diagnosis of PCOS. Ratios less than 3 do not exclude the diagnosis. Routine measurements of FSH and LH are therefore not needed.

Fasting plasma glucose and lipid profiles are not necessary for the diagnosis of PCOS. However, in patients suspected to have PCOS, insulin resistance, or both, these profiles are helpful to define the presence of metabolic risk, which over the long term can significantly affect a patient’s morbidity and mortality.

Ultrasound evaluation of the ovaries, adrenals, or both, may be useful for screening if the symptoms or biochemical levels suggest the presence of a neoplasm. Pelvic sonography findings have been included in the criteria for the diagnosis of PCOS.