Unreliable tests, conflicting guidelines create difficulty in management of hirsutism

American Association of Clinical Endocrinologists 20th Annual Meeting

SAN DIEGO — The diagnosis and management of hirsutism in women can be complicated for endocrinologists due to variable screening and discrepancies in guidelines. A speaker here outlined the major issues and provided suggestions when managing hirsute women.

“The challenges we face are whom to evaluate, what type of screening to use, who needs metabolic screening, and what are the best treatment modalities,” Andrea Dunaif, MD, Charles F. Kettering professor of endocrinology and metabolism at Northwestern University Feinberg School of Medicine, Chicago, said during a presentation.

Women with hirsutism most commonly present with the classic chronic anovulatory form of polycystic ovary syndrome. This condition is easy to diagnose in the office by obtaining menstrual history and hormonal testing, Dunaif said. Ovarian ultrasound is not necessary for the management of hirsutism since PCO morphology is a common finding in women with normal menstrual cycles and is not a marker for metabolic abnormalities, she said. Dunaif explained that the NIH criteria for the diagnosis of PCOS, hyperandrogenism and chronic anovulation with exclusion of disorders of the ovary, adrenal and pituitary identify the subset of hirsute women at risk for glucose intolerance and dyslipidemia.

Evaluation issues

Guidelines from The Endocrine Society recommend that physicians base the type of evaluation used on the severity of hirsutism. For example, women with mild hirsutism who have regular menstrual cycles do not require hormonal evaluation and can be administered trial therapy.

“My concern here is that the hirsutism really depends on the target tissue sensitivity to androgens rather than on circulating levels, and you can have fairly substantial androgen excess and modest hirsutism,” Dunaif said. “I think that we have to use hirsutism as an indicator of androgen excess and that it is appropriate to do at least some biochemical assessment of androgen levels in affected women, particularly since women with a history of regular menses can still have anovulation.”

In contrast, AACE and the Androgen Excess and PCOS Society recommend measuring levels of total and bioavailable testosterone and proceeding to tests for other conditions such as glucose intolerance or congenital adrenal hyperplasia depending on the presence of certain risk factors.

However, Dunaif said testosterone assays are problematic, and physicians should be aware of specific issues that could affect the accuracy of such tests. For instance, assays used by many commercial and hospital laboratories lack the sensitivity to accurately measure testosterone levels in the normal and hyperandrogenic female range and, therefore, have large coefficients. Liquid chromatography mass spectroscopy assays are theoretically superior for the measurement of circulating testosterone levels in women, but even these assays can have poor precision for measuring testosterone levels in the female range, she said. AACE, The Endocrine Society and the CDC are also collaborating to help create more standard and reliable methods for testosterone assays.

Screening for glucose intolerance and dyslipidemia is also recommended in women who fulfill NIH criteria for PCOS, particularly if they are obese, according to Dunaif. Many physicians also question whether screening for insulin resistance is appropriate. However, there is no accurate office-based test to diagnose insulin resistance; fasting and glucose-stimulated insulin levels can be misleading. The presence of features of the metabolic syndrome suggests that the patient is insulin-resistant. Further screening for ovarian or adrenal androgen-secreting neoplasms is indicated if total testosterone or dehydroepiandrosterone levels are markedly elevated; however, stimulation and suppression tests to localize the source of androgen excess can be misleading, Dunaif said.

Appropriate treatments

For a woman with hirsutism but no metabolic issues, Dunaif recommended suppressing androgen production and bioavailability with a low estrogen dose oral contraceptive preparation containing a second-generation progestin, since newer progestins may increase the risk for venous thromboembolism. Spironolactone, an aldosterone antagonist, which is also antiandrogenic in higher doses, can be added in women with moderate to severe hirsutism. Spironolactone is not FDA approved for the treatment of hirsutism, but has a good safety profile and similar efficacy to cyproterone acetate, which is not available in the US, and flutamide, which has substantial risk for hepatotoxicity.

The only recommended insulin-sensitizing drug for the treatment of PCOS is metformin because of concerns about cardiovascular safety of the thiazolidinediones. Metformin is less effective for the treatment of hirsutism than antiandrogens.

“Extreme caution should be exercised if metformin is combined with antiandrogens to ensure adequate contraception since antiandrogens can cross the placenta and feminize a male fetus,” Dunaif said.

Furthermore, for obese women, Dunaif recommended weight loss, explaining that as little as a 7% reduction in body weight can be beneficial. – by Melissa Foster

For more information:

• Dunaif A. Meet the experts. The hirsute woman: Challenges in the evaluation and management. Presented at: American Association of Clinical Endocrinologists 20th Annual Meeting; April 13-17, 2011; San Diego.

Disclosure: Dr. Dunaif reports no relevant financial disclosures.

This is a problem that we seem in many patients who come into our office. Many women are faced with excessive hair growth, and the important thing to do is differentiate: Is this within normal limits or do we have an endocrine abnormality here that needs to be addressed? It is actually a very common issue.

– Richard Dolinar, MD
Endocrine Today Editorial Board member

Disclosure: Dr. Dolinar reports no relevant financial disclosures.

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