Review Nixes 'Female Viagra' Patch After Surgical Menopause

LONDON, March 6 -- Testosterone skin patches for women may have little impact on waning libido after hysterectomy, researchers said

Relatively low effectiveness, large placebo responses, and lack of long-term safety data led to a recommendation against transdermal testosterone for female sexual dysfunction in a review edited by Ike Iheanacho, M.B.B.S., in the March issue of Drug and Therapeutics Bulletin.

The testosterone patch, marketed as Intrinsa in Europe for women with hypoactive sexual desire disorder after surgically-induced menopause, was rejected by the FDA in 2004. The agency cited concerns about unknown cardiovascular and breast cancer risks with chronic use, particularly since concomitant estrogen therapy would be required.

Although some studies have linked postmenopausal sexual dysfunction to low circulating concentrations of testosterone, Dr. Iheanacho's group (the authors were not named) highlighted flaws in the clinical trial evidence that the patch could reverse this effect.

Randomized controlled trials comparing the patch to placebo have included only a "highly selected" group of women without any physical or psychological conditions that could cause low sexual desire and who were in stable, monogamous sexual relationships, they said.

Furthermore, some of the studies diagnosed hypoactive sexual desire disorder strictly though self-reporting or short, nonvalidated questionnaires.

The reviewers said large placebo responses suggested that the very act of participating in the trial or the visible presence of a patch -- whether active or placebo -- might have stimulated dialogue and sexual activity between trial participants and their partners. That "undermines the idea that these women had a chemical deficiency that needed rectifying," they noted.

The FDA and European drug-licensing agency have questioned whether women enrolled were truly sexually dysfunctional, given the baseline of two to three sexual events per month seen in some of the trials.

The agencies also expressed doubt about whether the small increases in sexual activity reported in the trials were clinically meaningful.

One of the two pivotal trials revealed an increase in the frequency of total satisfying sexual activity with the testosterone patch among women with hypoactive sexual desire disorder after surgically-induced menopause (increase of 2.10 episodes per four weeks from baseline of 2.82 versus increase of 0.98 from 2.94 baseline with placebo, P=0.0003).

The second key trial also showed a significant increase in total satisfying sexual episodes during weeks 21 to 24 with the patch compared with placebo (mean increase 1.56 versus 0.73 episodes per four weeks, P=0.001), but without reporting baseline levels.

Another area of concern has been adverse effects. Unwanted androgenic effects -- including acne, hirsutism, alopecia, breast pain, weight gain, insomnia, voice deepening, and migraine -- occurred in between one in 10 and one in 100 women on the transdermal testosterone patch.

Although typically mild, the androgenic effects reported in the two pivotal trials did not fully resolve for 27% of patients with acne, 57.5% with hirsutism, 39% with alopecia and 40% with voice deepening.

Because the treatment in the trials lasted no longer than 24 weeks, "long-term safety cannot be assured," the reviewers cautioned.

"For all these reasons, we cannot recommend Intrinsa for the use in women with sexual dysfunction," they concluded.

Paying attention to women's personal, relationship, partner function, medical, and contextual issues may be more fruitful than pursuit of hormonal status, they suggested.