The testosterone patch improves sexual function and decreases emotional distress in postmenopausal women who have hypoactive sexual desire disorder, but the patch's long-term safety needs to be assessed, according to an international study of more than 800 women.

“The increase in the frequency of satisfying sexual episodes was modest but appeared to be clinically meaningful,” said Dr. Susan R. Davis of Monash University, Prahran, Victoria, Australia, and her associates.

This is the first large-scale, phase III clinical trial of testosterone therapy that involved postmenopausal women who were not taking concomitant estrogen. The results “indicate that exogenous estrogen or combined estrogen plus progestin are not required for testosterone to be effective in the treatment of hypoactive sexual disorder,” the authors wrote.

However, “additional data are needed to assess the long-term safety of testosterone use in women with estrogen depletion,” they added.

Of particular concern is the possibility that testosterone without concomitant estrogen may have adverse effects on the breast and endometrium. In this study, four cases of breast cancer occurred in women on active treatment, compared with no cases in women taking placebo, and vaginal bleeding also was significantly more common with active treatment.

The study involved women aged 20–70 years who had surgically induced menopause of at least 1 year's duration, and women aged 40–70 years who had natural menopause of at least 2 years' duration. These subjects all had hypoactive sexual desire and were treated at 65 medical centers throughout the United States, Canada, Australia, the United Kingdom, and Sweden between 2004 and 2006.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., which also was involved in study design and data collection, and conducted the data analysis. Procter & Gamble makes Intrinsa, a testosterone patch that has been approved by the European Medicines Agency for treatment of hypoactive sexual desire. A Food and Drug Administration advisory committee recommended against approval of the drug for the U.S. market in 2004.

In the study, 814 women were randomly assigned to use a 150-mcg testosterone patch, a 300-mcg testosterone patch, or a placebo patch every day for 1 year. The efficacy analysis was performed at 24 weeks, after which the effect of testosterone tends to plateau; the safety analysis was performed at 1 year. A total of 71% of the study subjects completed 24 weeks, and only 57% completed the full year.

Compared with the placebo group, both groups on active treatment reported significant increases in sexual desire and frequency of satisfying sexual episodes, as well as decreases in personal distress related to sexual function.

The improvement in frequency of satisfying sexual episodes was “numerically modest,” at only 1.4 more such episodes per month. However, this amount has been shown to be clinically meaningful in previous studies, Dr. Davis and her associates said (N. Engl. J. Med. 2008;359:2005–17).

Treatment effects did not differ between women who had undergone surgical menopause and those who had undergone natural menopause.

The overall incidence of adverse effects was similar among the three groups. The most common reasons for withdrawal from the study were patch-site reactions and androgenic events, principally the growth of facial hair.

Four women receiving active treatment developed breast cancer, compared with none receiving placebo. The size of the study groups was too small to allow for analysis, and this excess could be the result of chance. But “the possibility of a causal relationship must be considered,” the researchers noted.

Nearly 11% of women with an intact uterus who used the higher dose patch reported vaginal bleeding, compared with fewer than 3% of the other two groups. All women with vaginal bleeding had ultrasonography and/or endometrial biopsy. There were no cases of endometrial hyperplasia or carcinoma.

In an accompanying editorial comment, Julia R. Heiman, Ph.D., of the Kinsey Institute for Sex, Gender, and Reproduction at Indiana University, Bloomington, said that it is reasonable to wonder whether an absolute increase in satisfying sexual episodes of only 1.4 per month is worthwhile.

“Although the report does not indicate whether the women were asked whether this change was meaningful for them, a review of the baseline data suggests it probably was, since the mean number of such episodes almost doubled for the high-dose group,” she said (N. Engl. J. Med. 2008;359:2047–9).

The “potentially worrisome” excess of breast cancer cases “cannot be ignored,” Dr. Heiman added.

They “suggest the need for caution in using testosterone until we understand more about its possible link with breast cancer and are better able to predict which patients are more likely to be subject to negative effects.”

Dr. Davis reports receiving consulting or lecture fees from Acrux Ltd., AstraZeneca Oncology Australia, Organon, and Procter & Gamble Pharmaceuticals, as well as grant support from AstraZeneca Pharmaceuticals, Novartis Oncology Australia, and Procter & Gamble Pharmaceuticals. Dr. Heiman reports receiving grant support from Pfizer, Bayer HealthCare, and Zestra Laboratories Inc.

Testosterone Patch Improves Sexual Function in Postmenopausal Women