Advocates crusade for gender equality in treating sexual dysfunction

Drug companies have been hotly pursuing a fix for female sexual dysfunction ever since Viagra was approved 16 years ago.

They keep falling short.

The letdowns have been seen as evidence that the fairer sex's sexual problems are tougher to define, diagnose, and safely treat than men's.

But now there's a new theory about why women and drug developers can't get any satisfaction:

The U.S. Food and Drug Administration is sexist.

"There are 26 drugs for [sexually dysfunctional] men, zero for women," said Irwin Goldstein, president of the Institute for Sexual Medicine in San Diego. "The FDA has gender issues."

"Women's sexual health is held to a different standard of risk-benefit by the FDA than male sexual health," said Sheryl A. Kingsberg, a clinical psychologist at University Hospitals Case Medical Center in Cleveland.

That contention has been made for years by experts who are also paid pharmaceutical consultants. But over the last six months, the complaint has grown into a testy advocacy crusade. Even the Score: A Campaign for Women's Sexual Health Equity was launched last month by women's groups, complete with a website (eventhescore.org), petition, and congressional supporters.

Although the website doesn't explicitly say so, the impetus for the campaign was the FDA's rejection late last year of flibanserin, a drug first tested as an antidepressant.

The FDA found flibanserin modestly effective at boosting libido, but worried about the once-a-day pill's side effects, including dizziness, nausea, and sleepiness.

The maker, Sprout Pharmaceuticals, appealed the rejection in December. Soon afterward, representatives of eight women's groups - including the National Organization for Women - had a tête-à-tête with FDA Commissioner Janet Woodcock.

"We were pleased, Dr. Woodcock, with your recognition that [the disparity in approvals] may signal gender bias, conscious or unconscious," the groups wrote the FDA chief after the meeting.

Publicly, the FDA has denied any prejudice. But in February, the agency agreed to reconsider flibanserin. In exchange, Sprout agreed to do three more small safety studies.

"We know sex is a bio-psycho-social process," said Sprout CEO Cindy Whitehead. "But we all bring biology into the bedroom. We need to address the biology. We can't keep up this idea that 'it's all in her head.' "

The equity campaign's mantra that men have 26 approved therapies while women have none is controversial.

Critics point out that the FDA has approved two treatments for female sexual problems - the EROS device that aids arousal by drawing blood into the clitoris, and Osphena, a daily pill that acts on estrogen receptors to relieve painful intercourse.

Critics also question the math. Josh Bloom, director of pharmaceutical sciences at the American Council on Science and Health, argued in his blog that the real number of male sex dysfunction drugs is five or six because "calling a pill by a different name doesn't make it a different drug."

By his count, there are four approved bloodflow-boosting drugs like Viagra (three are sold under nine additional trade names), many products containing the blood vessel-widening compound alprostadil, and a slew of testosterone replacement therapies.

Including testosterone is dubious, critics say, since it treats testosterone deficiency, which has varying symptoms including fatigue, osteoporosis, and low libido. If "Low T" products count, then menopausal hormone therapies should be toted up on the female side.

"This whole pseudo-quantitative approach is deceptive and deceitful. They're not counting fair," said Leonore Tiefer, a New York University psychiatry professor and sexuality researcher.

Most drugs in development for female sexual dysfunction - and there are at least seven - are permutations of the ones that help men, as well as mood-altering chemicals.

In clinical studies, all of them work. Sort of. The problem is, placebo also works, proving the role of that vital female sex organ - the mind.

Intrinsa, the Procter & Gamble testosterone patch, was barely better than placebo at raising the number of "satisfying episodes" of sex per month. It is the only product besides flibanserin to complete late-stage testing and seek FDA approval.

The FDA spurned the patch in 2004, concerned that testosterone could raise breast cancer and heart disease risks.

In 2011, BioSante Pharmaceuticals completed costly studies that demonstrated LibiGel, a testosterone gel, was safe. Alas, the final pivotal tests showed the gel was no better than placebo in the bedroom.

"LibiGel was a surprise and a disappointment and a shame," said Kingsberg, at Case Medical Center. "It had great safety data on more than 4,000 women."

The quintessential male hormone remains in the running. Trimel Pharmaceuticals is testing Tefina, a nasal spray for use as needed by women with orgasm difficulties. The Canadian company recently got FDA approval of a version for men, Natesto, to treat Low T.

Flibanserin, meanwhile, increased satisfying sex episodes by one more than placebo over 28 days in a key 24-week study.

"We don't make women hypersexual," said Whitehead, the Sprout CEO. "But it raises them back into the normal range. It was a meaningful effect to these patients."

While the equity campaign offers "facts" about the high prevalence of women suffering sexual problems, scientific understanding remains fuzzy.

In 2000, the FDA issued preliminary guidelines to help companies design trials. It said the definition of female sexual dysfunction was evolving, but had four components: decreased desire, decreased arousal, sexual pain, and orgasm difficulties.

The FDA withdrew that view about a decade later.

Why?

"Because it is outdated and no longer in line with the FDA's current thinking," spokeswoman Andrea Fischer wrote in an e-mail.

What is that current thinking?

"The FDA will notify the public . . . if the agency publishes a new draft guidance," Fischer e-mailed.

Meanwhile, the American Psychiatric Association's recently revised manual eliminated "hypoactive sexual desire disorder" - or low libido, the problem flibanserin treats - in favor of the combined "female sexual interest/arousal disorder."

If flibanserin prevails, "it would be approved for a nonexistent condition," critics of the equity campaign wrote the FDA.

Those critics - including Tiefer and the National Women's Health Network - lauded the FDA for setting a high safety bar, given flibanserin's "worrisome side effect profile and unknown longterm effects."

Sprout is now doing tests to see if its drug impairs driving, if it interacts with other drugs, and how the liver metabolizes it. The Raleigh, N.C., firm expects to resubmit to the FDA late this year.

215-854-2720 @repopter