EVIDENCE-BASED ANSWER
The evaluation of hirsutism should begin with a history and physical examination to identify signs and symptoms suggestive of diseases such as polycystic ovarian syndrome (PCOS), hypothyroidism, hyperprolactinemia, hyperandrogenic insulin-resistant acanthosis nigricans (HAIR-AN) syndrome, androgenic tumors, Cushing’s syndrome, or congenital adrenal hyperplasia (CAH). Findings suggestive of these diseases include rapid or early-onset hirsutism, menstrual irregularities, hypertension, severe hirsutism, virilization, or pelvic masses (strength of recommendation [SOR]: B, based on a cohort study in a referral population) (TABLE). Hirsutism with unremarkable history and physical exam findings should be evaluated with a serum total testosterone and dehydroepiandrosterone sulfate (DHEAS) level (SOR: B, based on a cohort study in a referral population).
TABLE
Differential diagnosis of clinically apparent androgen excess
| DIAGNOSIS | INCIDENCE | KEY HISTORY/EXAM FINDINGS | ADDITIONAL TESTING |
|---|---|---|---|
| Polycystic ovarian syndrome | 82.0% | ± irregular menses, slow-onset hirsutism, obesity, infertility, diabetes, hypertension, family history of PCOS, diabetes | Fasting glucose, insulin and lipid profile, blood pressure, ultrasound positive for multiple ovarian cysts |
| Hyperandrogenism with hirsutism, normal ovulation | 6.8% | Regular menses, acne, hirsutism without detectable endocrine cause | Elevated androgen levels and normal serum progesterone in luteal phase |
| Idiopathic hirsutism | 4.7% | Regular menses, hirsutism, possible overactive 5 alpha-reductase activity in skin and hair follicle | Normal androgen levels, normal serum progesterone in luteal phase |
| Hyperandrogenic insulin-resistant acanthosis nigricans (HAIR-AN) | 3.1% | Brown velvety patches of skin (acanthosis nigricans), obesity, hypertension, hyperlipidemia, strong family history of diabetes | Fasting glucose and lipid profile, BP, fasting insulin level >80 μIU/mL or insulin level >300 on 3-hour glucose tolerance test |
| 21-hydroxylase non-classic adrenal hyperplasia (late-onset CAH) | 1.6% | Severe hirsutism or virilization, strong family history of CAH, short stature, signs of defeminization, more common in Ashkenazi Jews and Eastern European decent | 17-HP level before and after ACTH stimulation test >10 ng/dL, CYP21 genotyping. |
| 21-hydroxylase-deficient congenital adrenal hyperplasia | 0.7% | See Late-onset CAH. Congenital virilization | 17-HP levels >30 ng/dL |
| Hypothyroidism | 0.7%* | Fatigue, weight gain, history of thyroid ablation and untreated hypothyroidism, amenorrhea | TSH |
| Hyperprolactinemia | 0.3%† | Amenorrhea, galactorrhea, infertility | Prolactin |
| Androgenic secreting neoplasm | 0.2% | Pelvic masses, rapid-onset hirsutism or virilization, over age 30 with onset of symptoms | Pelvic ultrasound or abdomen/pelvic CT scan |
| Cushing’s syndrome | 0%‡ | Hypertension, buffalo hump, purple striae, truncal obesity | Elevated blood pressure, positive dexamethasone suppression test |
| *Five patients were previously diagnosed with hypothyroidism and 1 patient was diagnosed as part of the work-up for a total prevalence of 6 in 873 or 0.7% although the de novo incidence was only 0.1%. | |||
| †Two patients were previously diagnosed with hyperprolactinemia and 1 was detected during the work-up for a total prevalence of 3 in 873 or 0.3% although the de novo incidence was 0.1%. | |||
| ‡No patients were identified with Cushing’s syndrome in this study. Other published reports vary from 0-1% (3). | |||
| Source: Azziz et al, J Clin Endocrinol Metab 20042; Azziz, Obstet Gynecol 2003.8 | |||
Evidence summary
Hirsutism is the presence of excess terminal hairs in androgen-dependent areas on a female, and can be measured objectively using a scoring system such as the modified Ferriman-Gallway (mF-G) score. This test is done by adding hair scores (0=none, 4=frankly virile) in 9 different body locations. A total score >8 is considered hirsute. The incidence of hirsutism in the US is about 8%, based on a prospective study of 369 consecutive women of reproductive age seeking pre-employment physicals in the southeastern US using the mF-G criteria.1
The causes of clinically apparent androgen excess, including acne and hirsutism, were evaluated in 1281 consecutive patients presenting to a university endocrinology clinic.2 Researchers excluded 408 subjects due to the inability to assess hormone status or ovulatory function. The remaining 873 women were assessed by clinical exam, mF-G score, serum total and free testosterone, DHEAS, and 17-hydroxyprogesterone (17-HP). Hyperandrogenism was defined as an androgen value above the 95th percentile of 98 healthy control women (total testosterone ≥88 ng/dL, free testosterone ≥0.75 ng/dL, or DHEAS ≥2750 ng/dL). Those with a 17-HP level >2 ng/mL had either a repeat 17-HP or adrenocorticotropic hormone (ACTH) stimulation test. Those with at least 2 total testosterone levels above 250 ng/dL or those with signs of an androgen-secreting neoplasm (eg, virilization) underwent a transvaginal sonogram and a CT scan of the adrenals. Patients with ovulatory dysfunction had a thyroid-stimulating hormone (TSH) and prolactin level drawn. If Cushing’s syndrome was suspected clinically, the subjects underwent an overnight 1-mg dexamethasone suppression test (TABLE). Of 873 patients, 75.5% had hirsutism and 77.8% had hyperandrogenemia. An identifiable disorder of androgen excess was found in 7%; functional androgen excess (principally PCOS) was identified in the remainder.
The incidence of endocrine disorders among patients presenting with hirsutism or androgenic alopecia was evaluated during a prospective study of 350 consecutive patients referred to an endocrine clinic in the UK.3 Testing included serum total testosterone, androstenedione, 17-HP, and DHEAS on 2 occasions. Patients also underwent high-resolution pelvic ultrasound. Further investigations were done only for those with abnormal hormone levels or clinical findings suggestive of a tumor. Of 350 women tested, 13 had a markedly elevated serum total testosterone level >5 nmol/L (150 ng/dL). A single total testosterone test identified 6 of 8 patients with an underlying endocrine disorder. The other 2 had either acromegaly or prolactinoma. The researchers concluded that clinical assessment and a single serum total testosterone level were sufficient to exclude enzyme deficiencies and virilizing tumors.