Flibanserin, a drug that revs up women’s sex drives, has been battling for five years to get the FDA’s stamp of approval.
Alice Mongkongllite / BuzzFeed News
At 45, Amanda Parrish had been divorced for nine years, and spent most of her free time in her hometown of Nashville, running after her four kids. She was, in her words, “your typical Southern Baptist soccer mom who didn’t really talk about sex.” Then she met Ben.
Ben was a lawyer, also divorced, with two kids from his previous marriage. Their shared experiences in failed marriages made it easy to connect, and they soon were married. Parrish describes the sex during their first few years together as “consistent, active, and awesome.”
Then, out of nowhere, came an increasing sexual malaise. “I was one of those ladies who would try to figure out how to go to sleep early,” Parrish told BuzzFeed News. “I started to do anything to avoid having sex — and when we did, it felt obligatory.”
The issue wasn’t physical attraction: Ben was as good looking as ever, and in great shape. And the problem didn’t extend to Parrish’s enjoyment of sex, since she could still climax. “The issue was getting me started,” she said. She felt off, like she’d lost an integral piece of her femininity.
Despite having an otherwise communicative relationship, she avoided talking to Ben about her plummeting sex drive. She didn’t even know how to think about it — was there something wrong with her body, or was it all in her head? And was there even a difference?
Afraid of what their waning intimacy might do to an otherwise healthy marriage, Parrish began desperately searching for solutions. She ordered bottles of libido enhancers online, but threw them away after getting “too freaked out” about where they came from. She asked her doctor to write an off-label prescription for testosterone, which has been shown to rev up female sex drives. The hormone shots made her feel physically energized in a way she hadn’t felt in years. But her libido remained flat. “It ended up working out better for me in the weight room than the bedroom,” Parrish laughed.
Her doctor asked about the obvious culprits: her full-time job, her six kids, the predictable dimming of the post-honeymoon period. But Parrish swore it was something deeper.
Less than a year later, she found herself enrolled in a clinical trial for a new drug called flibanserin, the so-called “female Viagra.” That was 2009. In the years since, flibanserin has sparked a national debate over the nature of female sexuality.
Last week, the drug was given its final shot at being approved by the Food and Drug Administration (FDA), after being rejected twice before. If approved, it will be the first drug authorized by the agency to treat sexual dysfunction in women, compared with nine prescription drugs available for men. Its manufacturers have been battling with regulators over whether female sexual desire should be treated with drugs. Can something as elusive as desire boil down to biology?
Low libido is the most common sexual complaint among women — and it’s not just Parrish’s middle-aged cohort feeling the squeeze.
About 10% of pre-menopausal women in the U.S. are diagnosed with “hypoactive sexual desire disorder” (HSDD), first defined in medical literature roughly 30 years ago.
People with HSDD are uninterested in sex regardless of mood or occasion, capped off with a heavy dose of distress and anxiety over doing the deed. Most importantly, their problem exists in the absence of any other notable culprits — psychiatric problems, for example, or drug side effects, or an inattentive partner.
The biological contributions to female desire are no better understood than the social ones, but they have the advantage of potentially being tweaked with drugs. While a testosterone patch for women was tested in 2004, it never made it to the U.S. market. A handful of other hormonal and non-hormonal drugs owned by small companies are now at various stages of clinical testing.
The drug farthest along in this category, by far, is flibanserin. The drug was originally tested, in 2006, as an antidepressant. It didn’t work well as a mood-lifter, but researchers noticed it had an intriguing side effect: Unlike most antidepressants, which squash libido, flibanserin seemed to do the opposite.
So in 2007, the drug’s manufacturer, a large German company named Boehringer Ingelheim, remarketed it as a sex-enhancing drug. The company ran two clinical trials in the U.S. and Europe testing the drug on 5,000 premenopausal women, and in 2010, submitted flibanserin’s application to the FDA.
If approved, the company knew, this drug could be big. Viagra, after all, had been a blockbuster drug for a decade, prescribed to more than 30 million men across 120 countries and raking in roughly $1.6 billion a year. Viagra works by increasing blood flow to the penis so men can have and maintain hard-ons during sex. Viagra’s manufacturer, Pfizer, also tested the drug in women with HSDD to see if — like in men — the female sex impulse could boil down to sheer hydraulics. And though Viagra did increase blood flow and circulation down south, it didn’t do anything to actually turn women on.
Although flibanserin is often referred to as the “female Viagra,” the drug doesn’t work at all like Viagra does. Instead, it has a much more elusive target: the brain. Specifically, flibanserin alters serotonin and dopamine levels to affect the brain circuitry that somehow drives pleasure and desire.
Advocates of flibanserin say that for too long, women’s sexual desires have been reduced to social and psychological factors. It’s time to stop ignoring female biology, they argue.
“Sex is complex,” Cindy Whitehead, CEO of Sprout Pharmaceuticals, the North Carolina company that now owns the drug, told BuzzFeed News. “We bring our religion, how we were raised, and what’s going in our lives into the bedroom. But men and women alike bring biology into the bedroom.”
But that leads to a sticky scientific question: How do you measure a drug’s effects on something so elusive as sexual desire?
Parrish came across the flibanserin clinical trial by accident, after seeing a pamphlet advertising it in her doctor’s waiting room.
She picked it up and began mentally answering its questions about low libido. “One by one I started thinking, This is me,” she said. She flagged the issue to her doctor, who eventually diagnosed her with HSDD. She signed up for the clinical trial right away.
One day about two weeks after starting on the once-daily drug, Parrish was driving and suddenly felt “the flutter,” she said. “For lack of a better word, I felt horny.” She pulled over and sent Ben a text while he was still at work: “Would you like to have me for lunch?”
From that point on, Parrish said, sex was totally invigorating. Rather than avoid it, she initiated it — often. Rather than go to sleep after a long day, she gladly stayed up for sex. She felt more spontaneous. She even sent Ben a pantygram.
“Within a month we were back to the point we were at when we first started dating,” Parrish said. She was relieved, she said, to find that the problem hadn’t all been in her head. “I’m not sure if, without the drug, Ben would have understood that it was my body doing this, not me.”
Every morning, she recorded and quantified her sex life in graphic detail in an e-diary — whether she initiated, used lube, or orgasmed, along with a numerical rating of the experience. This constant logging, along with sporadic headaches, were the only downsides of being in the trial, she said.
Parrish was one of 1,600 women in the trial. The results looked good: The women taking a full dose of the drug every day for six months seemed to show an increased sex drive and less distress over sex. But there was a strong placebo effect as well: The e-diary scores of sexual desire were no different in women taking flibanserin and those taking sugar pills. Interestingly, similar placebo effects had cropped up in some Viagra trials. When it comes to sexual desire, regardless of gender, it’s hard to draw the line between changes in the body and those in the mind.
Parrish didn’t know (and still doesn’t know) whether the pills she popped every night were the real thing or a placebo, even though she was invited to check once the trial was over. Given her total turnaround, she decided she didn’t need to check: She was convinced they were flibanserin. Had the trial doctors let her, she would have taken them forever.
But in 2010, after being on the drug for eight months, Parrish had to send the drugs back. The FDA had rejected Boehringer Ingelheim’s application to market flibanserin.
Part of the problem, the FDA said, was how to measure an increase in libido in the first place.
While Viagra has a shining beacon of an indicator in men — the undeniable presence of a hard-on — female sexual desire is more difficult to quantify. Parrish had felt totally changed by her experience, but when the results from all of the participants were tallied, it wasn’t enough to prove the drug worked.
Although it rejected the flibanserin application, the FDA wasn’t dismissing the importance of HSDD: In 2012 the agency highlighted female sexual dysfunction as one of 20 disease areas it was prioritizing.
“The FDA has acknowledged it’s a problem — that’s not up for debate,” Anita Clayton, a psychiatrist at the University of Virginia who conducted some of the flibanserin trials, told BuzzFeed News. “But how do we measure that, and how do we say what’s meaningful?”
After the failed trial, Sprout Pharmaceuticals bought the rights to the drug and launched a clinical trial with more rigorous surveys to quantify sexual desire. This final trial tested over 1,000 women looking at three factors in particular — increased desire, lowered distress, and a higher number of “satisfying sexual events.”
Although Sprout’s new trial showed promising results, flibanserin was by no means a cure-all. About 10% of women dropped out of the six-month trial because of side effects. Women on the drug showed a 37% boost in sexual desire, a 37% increase in satisfying sexual events, and a 21% decrease in sexual distress, and all of these were significantly different than the results of the placebo group.
Despite these encouraging results, in 2013 the FDA again rejected flibanserin, this time due to side effects such as sedation, dizziness, nausea, and rare respiratory infections. Long-term safety concerns are crucial for a drug that is a once-a-day pill (as opposed to an on-demand libido booster, like Viagra). But the safety question has made many women infuriated at a government agency they view as making sexist decisions about the nature of sexuality.
Sprout, Clayton, and an advocacy group called Even the Score (partially funded by Sprout) say there is a troubling disparity between FDA-approved treatments for sexual dysfunction in men versus women. Men have nine medications on the market to treat erectile dysfunction issues — and more than a dozen others if you include generics and various combinations of treatments. Besides two drugs that treat post-menopausal women who have pain during sex, women have no drugs for boosting sexual pleasure.
As far as safety, these advocates point to the long list of side effects attached to Viagra: blindness, perma-erections that can last over four hours, and hearing loss. In comparison, the side effects of flibanserin seem tame.
“Flibanserin’s top risks are the same as taking over-the-counter Claritin, something considered by 99% of people to be completely safe,” Susan Scanlan, Even the Score’s campaign chair, told BuzzFeed News. “Men are willing to take risks that the FDA, in their paternalistic way, won’t allow women to take.”
Scanlan also points to Europe, where a testosterone treatment called Intrinsa is widely available for women with low libido. Intrinsa hit a wall with the FDA when the agency asked for further safety tests over a period of five years. These extra tests would have cost too much, so the company abandoned the U.S. market altogether.
“We have deeply entrenched sexism in the U.S., and it goes into our institutions like the FDA as well,” Clayton said. “This idea that women somehow need to be protected from a decision that they might make with their doctors doesn’t make sense to me.”
Sprout appealed the FDA’s rejection, and last Tuesday submitted two additional clinical safety trials testing next-day driving abilities — part of concerns about sleepiness — and the drug’s ability to be metabolized in women with rare genetic disorders.
The FDA is expected to deliver its final verdict on flibanserin by August. Because the drug is currently under review, the agency declined to comment on any of the specific allegations about its effectiveness. However, in a statement about its actions toward female sexual dysfunction drugs in general, the FDA strongly defended itself.
“The agency evaluates drugs based on science and strongly rejects claims of gender bias,” a spokesperson said.
Some women vehemently disagree that the success of flibanserin is a women’s rights issue.
They argue that HSDD is a matter of personal responsibility — that it’s up to women themselves to fix the likely many-layered issues leading to problems in the bedroom. In an age of overmedicalization, detractors add, pharmaceutical companies have a vested interest in profiting from low libido, which shouldn’t be labeled as a disorder in the first place.
“There’s a major problem with the blurring of the boundaries between the range of what it means to be a normal human being, and whether this is actually a medical treatment that requires pharmaceutical treatment,” Barbara Mintzes, an assistant professor at the University of British Columbia, told BuzzFeed News. “You get a sort of selling of the condition in order to sell the drug.”
These sentiments were echoed last October at a two-day HSDD workshop hosted by the FDA. Along with scientists and doctors, hundreds of patients were invited to share their personal experiences of living with the condition. But some also spoke out against what they saw as a shaming approach to low libido that encouraged women to stay quiet and pop a pill, sometimes just to keep their rocky marriages afloat.
One woman stood up to the podium and listed the various ways she had overcome her low sex drive — without any help from a pharmaceutical drug:
“Switching boyfriends, chocolate, coffee, certain episodes of Grey’s Anatomy, pornography, upgrading my vibrator, the phrase ‘A little to the left,’ the phrase ‘Not so hard,’ the phrase ‘I love you,’ reading Fifty Shades of Grey, a removable shower head, having tips from my girlfriends, having backrubs, back scratches, a good night sleep and absence of judgment from my boyfriend and an absence of judgment from my friends, a defiance of judgment from society, and an acceptance of myself and the libido I came with.”
On that last point, of libido “acceptance,” some contend that drugs like flibanserin do more to stigmatize female sexuality than support it.
“This approach assumes that there’s a certain sexual drive that’s normal and that if a woman is interested in sex less than that, then that’s abnormal,” said Mintzes. “It seems to me that that’s wrong. That certainly isn’t the way that you work towards sexual equality.”
That’s not how Parrish sees it. She and her husband were also at the FDA meeting. “I was offended, frustrated, and angry at a lot of stuff said at that meeting by women who were not diagnosed with this dysfunction,” Parrish said.
What they said reminded her of arguments used by opponents to antidepressants, who claim that Big Pharma is exploiting people who should be pulling themselves up by their bootstraps. HSDD, she said, doesn’t deserve that stigma, either.
“People are out there who have conditions who don’t seek treatment because they are afraid to,” she said. “Why deny people that?”
