FDA Raises Questions About Safety, Benefits of Female Testosterone Patch

FDA "appears to be striking a skeptical tone" about the safety and benefits of Procter & Gamble's Intrinsa testosterone patch, which would be the first of the so-called "female Viagra" therapies that are intended to "boost women's sex drives" with male hormones, the Wall Street Journal reports (Ellison, Wall Street Journal, 12/2).

An FDA advisory committee on Thursday will meet to evaluate Intrinsa, which has been granted "fast-track" consideration by FDA. P&G is seeking approval for the drug as a treatment for sexual dysfunction in women who have had their ovaries removed and experienced "surgical menopause." The patch gradually releases a small amount of testosterone, which replaces the hormones lost from ovary removal. According to P&G, about 10 million U.S. women have had their ovaries removed, about 20% of whom may have what the company has labeled "hypoactive sexual desire disorder." P&G is one of about 10 companies developing female sexual dysfunction treatments; none of the other products is expected to reach the market before 2006. Some analysts predict that the female sexual dysfunction market could grow to $1 billion in the next decade.

P&G conducted two clinical trials of Intrinsa involving a total of 1,095 surgically menopausal women. One study found that women wearing the patch reported a 74% increase in satisfying sexual encounters, at an average of 4.92 over a four-week period, compared with a 35% increase to 3.8 encounters among the placebo group. While the trial subjects noted only mild side effects, past studies have shown testosterone supplements for women can result in deepened voices, facial hair and balding. P&G currently is testing the drug on naturally menopausal women (California Healthline, 12/1).

If FDA approves the drug, it could reach the market as early as January (Peale, Cincinnati Enquirer, 12/2).

Review documents posted on FDA's Web site Wednesday noted that the P&G trials of Intrinsa may have found a statistically significantly benefit for Intrinsa, but it was unclear whether the results were "clinically meaningful." FDA also noted that the panel should review the potential long-term risk of using estrogen and testosterone together. Previous studies have found that hormone replacement therapies with estrogen can lead to increased risks of breast cancer and cardiovascular disease.

"It is unknown whether the addition of a different hormone, testosterone, might have similar and unanticipated adverse effects that have not been demonstrated" in P&G's studies, the review documents state. FDA also noted that the studies included a "very small number of subjects who have been treated beyond a year" (Wall Street Journal, 12/2). FDA said that such short-term studies "may not provide adequate estimates of the risks of hormonal therapy" (Rubin, USA Today, 12/2).

P&G spokesperson Elaine Plummer said that the company had anticipated FDA's questions and would address them at Thursday's hearing (Wall Street Journal, 12/2).

Irwin Goldstein, editor in chief of the Journal of Sexual Medicine, noted that P&G's trials, as suggested and monitored by FDA, relied on women to define "satisfying sexual events," which could be influenced by the women's sexual partners. "For whatever reason, in the knowledge and experience of the FDA, they wanted a countable, diary-based, as-it's-happening outcome measure to be the primary outcome measure. And those kind of measures aren't very sophisticated" (Henderson, AP/South Florida Sun-Sentinel, 12/2).

According to the Journal, "[m]any analysts" believe that in light of the observed risks of hormone replacement therapies and the "aftermath" of Merck's September withdrawal of its painkiller Vioxx, FDA would "tread carefully before giving Intrinsa a green light." While the company has proposed a program that would monitor the patch's safety after it has reached the market, FDA's Office of Drug Safety said that the program "was unlikely to provide adequate information about potential risks of the product." ODS recommended FDA delay approving Intrinsa until P&G performs a long-term, randomized, controlled study of the drug's safety (Wall Street Journal, 12/2).

According to the New York Times, FDA staff "often ten[d] to be more critical of drugs than the advisory panels, which are made up mostly of practicing physicians" (Pollack, New York Times, 12/2). The Washington Times reports that some experts have said the advisory panel could call for as much as a year of further evaluation before recommending Intrinsa for approval (Howard Price, Washington Times, 12/2).

Plummer said that despite FDA's concerns, the Intrinsa trials found a "very meaningful" benefit for "a lot of women" (Wall Street Journal, 12/2). Plummer also noted that women in the trials found Intrinsa had benefits beyond the increased number of satisfying sexual episodes, including "significant improvements" in arousal, orgasms, self-image and distress levels (USA Today, 12/2).

P&G spokesperson Mary Johnson said the company plans a marketing campaign to inform doctors and women about the proper use of Intrinsa (California Healthline, 12/1). P&G also plans to conduct a three-year safety study of Intrinsa involving 321 women and a five-year post-marketing study to track Intrinsa users' rates of heart disease and breast cancer (AP/South Florida Sun-Sentinel, 12/2).

According to the New York Times, some experts are concerned that Intrinsa will be used "as a means of enhancing sex by women who do not have hypoactive sexual desire disorder."

Lenore Tiefer, a New York University psychologist and sex therapist who will speak at the advisory panel hearing, said, "The off-label uses of this is obviously where [P&G is] heading." Tiefer said that she was not sure "hypoactive sexual desire disorder" was even a condition that could be treated through drugs. "There's an endless number of reasons that people can lose their sexual desire," she said, adding that Intrinsa is a "not-well-understood drug for a not-well-understood condition" (New York Times, 12/2).

Tiefer also has noted that while the drug may increase desire by one more sexual episode a month, women would have to wear the patch for several months before it starts to take effect (American Health Line, 12/1).

Sheryl Kingsberg, a psychologist at Case Western Reserve Medical School who worked on the Intrinsa trials, said, "This is not a manmade disorder to create a market. Women come into my office every day complaining they've lost their sexual desire and they want it back" (New York Times, 12/2). Goldstein added that Intrinsa is the "nuclear bomb of women's sexual health" that could transform female sexual dysfunction into a curable disease (Johnson, Boston Globe, 12/2).

However, Amy Allina, program and policy director of the National Women's Health Network, said, "We're going to have to look beyond medical solutions if we really want to deal with these problems" (USA Today, 12/2).