What About a Testosterone Patch for Women?

Abstract & Commentary

By Eileen C. West, MD, Director, Primary Care Women's Health, Clinical Assistant Professor, Internal Medicine/Obstetrics and Gynecology; University of Oklahoma Health Sciences Center, Oklahoma City. Dr. West reports no financial relationship to this field of study.

Synopsis: In this Phase III drug trial, use of a testosterone patch increased desire and the frequency of satisfying sexual activity in naturally menopausal women with hypoactive sexual desire disorder.

Source: Shifren JL, et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study. Menopause. 2006;13:770-779.

Hypoactive Sexual Desire Disorder (HSDD) refers to a persistent decrease of interest in or aversion to sexual contact which causes distress. The affected person has a low level of sexual desire that is manifested by a failure to initiate or be responsive to a partner's initiation of sexual activity. HSDD becomes a diagnosable disorder when it causes marked distress or interpersonal instability.1 It occurs in both genders. It is the most common of female sexual disorders, affecting more than 20% of all women. Primary HSDD can be the result of early sexual trauma, repressive family attitudes about sex, or a history of painful intercourse. Acquired HSDD is associated with boredom in the relationship with a sexual partner. Depression must be ruled out before making the diagnosis. Younger, surgically postmenopausal women are at high risk. Priapism, vaginismus, hypogonadism, antidepressant use, substance abuse, prolactinoma, genital infections, diabetes mellitus, and chronic renal disease may all be associated with HSDD.

Treatment thus far has focused on the source of the disorder, using medical therapy or behavioral psychotherapy. Women exhibit falling androgen levels as they age and total testosterone concentrations of women older than age 50 are half that of women in their 20s.2 What's more, menopausal hormone therapy with oral estrogen increases sex hormone binding globulin (SHBG) levels, decreases luteinizing hormone secretion, and lowers testosterone production and availability.3 In cases where insufficient testosterone is suspected as a possible cause, serum androgen levels are tested. However, low libido and serum testosterone levels do not correlate well.

Dr. Shifren, assistant professor of obstetrics and gynecology at Harvard Medical School, and colleagues have now published a randomized, double-blind, placebo controlled study to evaluate the efficacy and safety of a testosterone patch for the treatment of women with HSDD after natural menopause. Although no androgen product is approved in the United States for the treatment of female sexual dysfunction, many women use compounded products and products intended for men. There is keen interest in testosterone testing and treatment. Androgen therapy seems to have most benefit in patients who have undergone early surgical menopause, and this study attempts to extend that use to naturally menopausal women.

This Phase III trial is the first large study of testosterone therapy among naturally menopausal women with HSDD on estrogen or combined hormone therapy.

In 549 menopausal patients taking estrogen (+ progesterone where indicated) application of a twice-weekly 300 microgram testosterone patch for 24 weeks increased the total number of satisfying sexual encounters and orgasms by one to two per month and lowered personal distress by 20%. It also improved circulating bioavailable testosterone. Estrogen levels and SHBG did not change. Most adverse events were mild or moderate and did not result in discontinuation of the study drug. Women grew slightly more facial hair, suffered site reactions, and were slightly more prone to acne, but did not experience deepening of the voice or alopecia. There were no significant changes in clinical laboratory values, including lipid profiles, carbohydrate metabolism, hematology, and liver and renal function, in either group.

Commentary

Think you have heard this somewhere before? Well, you have. In fact, these data were released in national conferences and widely promoted by the pharmaceutical company nearly two years ago when the testosterone patch being studied was up for FDA approval. Finally, we all hoped—a quick fix for low sex drive! Despite the study showing that sort-term use is safe and effective, the US Food and Drug Administration rejected approval of transdermal testosterone use for HSDD, citing the lack of long-term safety data. Thus far, in all of the transdermal testosterone trials, clinical improvement is seen only with higher than normal blood levels of testosterone. The risks of these higher testosterone levels are unknown. These medicines can decrease HDL (good cholesterol) levels significantly. Thus, testosterone use in women remains experimental. As most are well aware, there has been much controversy about treatment with other exogenous hormones, particularly since the publication of the Women's Health Initiative. Dr. Shifren responded to the criticism that modest gains may not outweigh unknown risks, "To focus on the one or two satisfying sexual events in 4 weeks is to miss the picture. We measured other aspects of sexual function, all of which were statistically significantly improved compared to placebo, such as sexual self-image, arousal, and orgasmic response." She feels that women and their physicians are capable of evaluating the risks and benefits of such therapies. The hormone controversy continues.

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR Fourth Edition (Text Revision). American Psychiatric Publishing; 4th edition, 2000.

2. Zumoff B et al. Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women. J Clin Endocrinol Metab. 1995:80:1429-1430.

3. Casson PR, et al. Effect of postmenopausal estrogen replacement on circulating androgens. Obstet Gynecol. 1997;90:995-998.