Female libido patch in limbo
In 1998, an eagerly anticipated pill to restore men’s sexual performance -- Viagra -- took six months to win marketing approval from the U.S. Food and Drug Administration. But more than a year after its maker applied for the FDA’s blessing, a medication shown to recharge the stalled sex drive of some women is riding a rockier road to approval.
Known as the Intrinsa patch, the product is designed to deliver small doses of testosterone through a woman’s skin, boosting the level of the male sex hormone in her bloodstream. All women produce testosterone. But most women’s testosterone levels decline with age, and surgical removal of the ovaries will cause a precipitous drop-off.
The frequent result is a condition known in medical circles as hypoactive sexual desire disorder, or HSDD. The dysfunction was not formally recognized in medicine until 1999, although by some estimates the condition affects about 11 million American women.
Women’s sexuality is complex, affected more deeply than men’s sex drive by mood, self-esteem and relationship issues. It has never been an easy thing to capture -- or to fix when it goes awry. It took years for the FDA and experts to devise ways to measure improvements in a woman’s libido, and many still argue that counting “satisfying sexual events” is a gauge better suited to men than women.
Now, with concern mounting over the long-term safety of new drugs, the safety of women’s testosterone use has become a new obstacle. Proponents of the patch, which include hysterectomy support groups and many gynecologists, say the timing of the product’s FDA review could not have been worse.
Last December, just weeks after the arthritis drug Vioxx was pulled from the market for safety concerns, an FDA panel gave the testosterone patch -- made by Procter & Gamble -- the equivalent of a blinking red light.
The panel recommended against approval until the safety of long-term use was better tested and understood, and members suggested that nothing short of a five-year study involving thousands of women could allay their concerns. Acknowledging the “huge demand” that would probably come with approval, panel members worried aloud that long-term use by millions of women might increase the rates of breast cancer, heart disease and stroke. In the years after hormone replacement therapy came into wide use, those illnesses saw a significant uptick -- a trend that was not recognized until 2004. Then, a study that had followed thousands of women for five years revealed the risks of boosting estrogen and progestin levels as a treatment for menopausal symptoms. The scientific about-face that followed was difficult for many physicians and their patients, who are wary of reliving the experience with testosterone.
The recommendation by the FDA’s panel of advisors was a major blow to the makers of Intrinsa. But with several clinical trials still underway, Procter & Gamble Pharma and Personal Health hopes that FDA will consider approval anyway. “We’re in talks with the FDA, working out a practical approach to address their concerns about safety,” says company spokeswoman Elaine Plummer, who adds that no studies to date have suggested serious negative effects.
Two new studies in recent months have reignited debate about Intrinsa, a product once hailed as “the female Viagra.” A study published last week in the Archives of Internal Medicine, and conducted by Cedars-Sinai Medical Center’s Dr. Glenn D. Braunstein and colleagues, found that women who used the patch for 24 weeks reported, on average, a 67% increase in their sexual desire, compared with a 48% increase in desire reported by women taking a placebo, or dummy pill. It also boosted the number of “satisfying sexual encounters” from an average of three per month to five -- slightly higher than the increase reported by women taking the placebo. A similar finding was reported in May by researchers at Baylor Medical College.
Accompanying the studies, however, were commentaries that reflected the crosscurrents that have buffeted Intrinsa on its path to market: a desire, on the one hand, to address the needs of women who suffer distress because of low sex drive, and, on the other, a rekindled caution about the risks of potential “lifestyle” drugs and the safety of medications that are rushed to market.
Writing in the Archives of Internal Medicine, Dr. Robert A. Vigersky of the Walter Reed Army Medical Center termed the benefits “modest” and cautioned that long-term use of the patch might put patients at greater risk of developing metabolic disease and cholesterol imbalance, as well as acne and unwanted hair growth. “These concerns demand long-term studies to avoid surprises” like the about-face that made millions of women abandon hormone replacement therapy in 2004, Vigersky wrote.
In an editorial in May’s issue of Obstetrics & Gynecology, Dr. David Guzick of the University of Rochester Medical Center chided the FDA for appearing to embrace a new safety standard for the testosterone patch. Guzick acknowledged that its effects on women’s sexual desire may not be overwhelming. But he wrote that women and their physicians should be given the chance to decide whether potential, but still unseen, risks might outweigh the possible benefits of a testosterone patch.
“The FDA advisory committee set the bar for a long-term trial so high that it is unlikely ever to be done,” wrote Guzick. Meanwhile, he noted, women already are taking testosterone to boost their sex drives, but in forms that have not been studied and are potentially far less safe.
Several additional studies of the testosterone patch are underway, though none as long or as large as some in and outside the FDA would wish. But many physicians who treat menopausal women question the FDA’s actions.
“Those standards are certainly not the standards for other products, to get that kind of extensive safety data,” says Dr. Margery Gass, a professor of obstetrics and gynecology at the University of Cincinnati College of Medicine who has consulted in the development of the patch.
