Practice Guideline Nixes Testosterone Therapy for Women

Marlene Busko

October 07, 2014

There is no evidence to support the use of testosterone or dehydroepiandrosterone (DHEA) by women with low levels of these hormones, with the possible exception of postmenopausal women distressed by and diagnosed with hypoactive sexual desire disorder, according to a new clinical practice guideline issued by the Endocrine Society.

The guideline, which updates a 2006 version, is published in the October issue of the Journal of Clinical Endocrinology and Metabolism.

"We don't have any [new] data to support the use of testosterone or DHEA in [healthy] women, and there's no evidence for an androgen-deficiency syndrome," writing chair and Endocrine Society vice president, clinical science, Margaret E. Wierman, MD, from the University of Colorado in Aurora, Colorado, told Medscape Medical News.

Specifically, testosterone is not recommended to treat women with infertility or cognitive, cardiovascular, metabolic, or sexual dysfunction (other than hypoactive sexual desire) or to promote bone health or well-being, she added.

Limited evidence suggests that postmenopausal women who are upset by and diagnosed with hypoactive sexual desire disorder might benefit from a 3- to 6-month trial dose of testosterone, according to the guideline. But these patients would have to be closely monitored for signs of androgen excess, such as acne or hirsutism, and the long-term safety, especially the risk for cardiovascular disease, is unknown.

Moreover, "the next bump in the road…is that currently, there are no [Food and Drug Administration] FDA-approved preparations [of testosterone for women] in the US," and the testosterone patch for women is no longer approved in Europe, Dr. Wierman told Medscape Medical News.

However, some physicians still opt to prescribe testosterone therapy to otherwise-healthy women on an off-label basis, she noted. "If you're going to use it off label by obtaining it through a compounding pharmacy (or through using a small amount of the male testosterone — which we didn't recommend), you really have to carefully monitor [testosterone levels]…so that you're not overshooting the normal range," she stressed.

Long-term Safety Concerns

The Endocrine Society, together with a number of other clinical agencies — the American Congress of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), European Society of Endocrinology (ESE), and International Menopause Society (IMS) — appointed a task force to reappraise the published data on testosterone and DHEA and update the previous guideline on androgen therapy in women.

A phase 3 study of the one product that was available for women with hypoactive sexual desire disorder — a testosterone patch called Intrinsa (Warner Chilcott) — showed that "it produced a modest effect on sexual function — an increase in 1 episode of satisfying sexual relations per month with no severe side effects over 1 year of therapy," Dr. Wierman said.

Approved in 2006 by the European Medicines Agency, Intrinsa was indicated for women with hypoactive sexual desire disorder and surgically removed ovaries.

But the FDA never approved this patch (Procter and Gamble) despite approval in Europe, because of concerns about breast cancer and potential long-term cardiovascular risk, Dr. Wierman noted.

And in 2012, the company requested withdrawal of the EU marketing authorization for this drug.

Testosterone Levels Do Not Correlate With Symptoms

"When we reviewed past studies, we found many women who had low testosterone levels measured by older or new techniques did not exhibit any signs or symptoms of concern," Dr. Wierman said. "As a result, physicians cannot make a diagnosis of androgen deficiency in women."

The normal range for the circulating level of testosterone in the blood is 250 to 800 ng/dL in men and more than 10-fold lower in women — 15 to 40 ng/dL — and only 0 to 20 ng/dL in postmenopausal women, which only very ultrasensitive new mass-spectroscopy assays can measure, she said.

"As endocrinologists, we feel that if something [such as testosterone level] is low, we should be able to bring it back to normal…and see…levels that correlate with signs or symptoms or response to therapy.…Now that we have very sensitive mass-spectroscopy assays, we might expect that we would see a clear response to testosterone in women with low levels. But that has not happened.

"Although limited research suggests testosterone therapy in menopausal women may be linked to improved sexual function, there are too many unanswered questions to justify prescribing testosterone therapy to otherwise-healthy women," Dr. Wierman observed.

And the few studies that have looked at giving DHEA, a precursor of testosterone, to women with low levels of testosterone have not shown any benefit either, she noted.

Meanwhile, the definition of hypoactive sexual desire disorder has changed, in going from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-4) to DSM-5, Dr. Wierman observed. "The new definition says it has to be distressing to the person, which makes sense."

Further research and ongoing improvements in androgen assays are needed to clarify the role of testosterone in women, the authors conclude.

Dr. Wierman has reported no relevant financial relationships. Disclosures for the coauthors are listed in the article.

J Clin Endocrinol Metab. 2014;99:3489–3510. Abstract

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