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Sex, Drugs, and Women's Desire

There may be other ways to boost sexual desire than the new pill, Addyi.

ByAmy NowogrodzkiNOVA NextNOVA Next
Sex, Drugs, and Women's Desire

It happened gradually when Barbara Gattuso was in her mid- to late-thirties. She was married and had three kids, the youngest of whom was a toddler. Her husband Greg was wonderful, and their marriage was going great. But she slowly lost her desire to have sex with him.

It wasn’t that she didn’t enjoy sex once it was happening. “When you’re in the act, you have desire. You like it when it’s being done,” she says. But beforehand, she felt no desire to have sex. This caused her “terrible stress.” She’d get up earlier in the morning than her husband, go to bed later, or pretend to be asleep just to avoid the possibility. “It was awful,” she says. “A horrible, horrible deception in a marriage.”

She talked to gynecologists, and none of them knew what to do. “If you find something, please let us know,” she says they told her. She called a “couple PhDs” who “claimed to be in sexual medicine.” When she explained her problem, she says they hung up on her. So she didn’t try sex therapy. She tried some over-the-counter remedies—nothing helped.

Barbara’s situation lasted for over 20 years. She never told Greg about it. One day in 2011, she saw a notice somewhere—on TV or in something she read, she doesn’t remember—of a clinical trial for a drug called flibanserin. “I was really excited,” she says.

Flibanserin was not yet approved, and it worked by altering levels of the neurotransmitters dopamine, norepinephrine, and serotonin. It was originally proposed as an antidepressant, first described in a 1997 paper, but it wasn’t found to be effective at treating depression in any of its nine Phase II trials. Many antidepressants carry a side effect of lower libido, and the later Phase II trials for flibanserin measured sexual dysfunction with an assessment that included the question, “How strong is your sex drive?” Women on flibanserin had higher sex drives than women on a comparable antidepressant, and, to the researchers’ surprise, higher sex drives than those on the placebo. So the Germany-based pharmaceutical company that owned flibanserin, Boehringer Ingelheim, began developing it as a drug to treat low desire.

Barbara hoped flibanserin would work to increase her desire or maybe as an antidepressant—either way, she could use it. “My dad was really ill at that time, and we lost our home in a fire. All this happened in six months.” She thought, “I have nothing to lose.”

Soon, Barbara was talking about her sex life in front of a couple hundred strangers. In a gray blazer with her blonde hair swept up, she looked determined and controlled sitting at the front of the FDA conference room in White Oak, Maryland. Other patients and their representatives clustered at circular tables in front. They were all there for the FDA’s patient-focused drug development public meeting on female sexual dysfunction.

Low desire has historically been considered a psychiatric condition, which means its diagnosis is defined in the Diagnostic and Statistical Manual, or DSM. When a group of experts met in 2000 to discuss updating the definition of female sexual dysfunction, “95 percent of them had financial relationships with the drug companies hoping to develop drugs for the very same condition,” wrote Ray Moynihan in his book Sex, Lies and Pharmaceuticals .

Moynihan began writing about the marketing of medical conditions as a journalist around 1999. “As I drilled into this story, I realized that the companies weren’t just sponsoring the science, they were actively helping to construct it,” he says. Pharmaceutical company employees and doctors with financial ties to the industry are directly involved in designing the questionnaires used to diagnose FSAID, the diagnostic criteria, and the outcome measures used to determine whether drugs are successful. “I was shocked to see how much the marketing and the science were merging,” Moynihan says.

“Companies weren’t just sponsoring the science, they were actively helping to construct it.”

At the FDA meeting, Barbara was required to disclose that her travel expenses were paid for by an event planning company called Veritas, which received funding from Sprout Pharmaceuticals, the company that bought the rights to flibanserin from Boehringer Ingelheim in 2011.

In the current edition, DSM-V, what Barbara experienced is called Female Sexual Interest/Arousal Disorder, also known as FSIAD. A woman has FSIAD when she has low or no desire for sex and that distresses her. Plenty of people, including those who identify as asexual, experience low desire but are not upset by this. It’s not a disorder unless it causes distress.

Why are some women bothered by low sexual desire? Lots of women probably have “desire discrepancy”—their desire level is different than their partner’s, which causes personal and interpersonal distress. Distress about sex is also linked with poor partner communication. There is some debate about whether low sexual desire in women is a medical, physiological problem in the brain or a sociocultural, interpersonal issue. Yet almost all the experts I talked to, on both sides of the debate, think that in at least some small percentage of women with severe sexual dysfunction, a drug could someday help.

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But there is disagreement about how large this segment is. Some experts without financial ties to pharmaceutical companies think that the majority of women with what has been called a disorder of low sexual desire actually have no abnormal physiological problem. Instead, these experts say these women are living in a sociocultural and medical system that encourages them to think of themselves as broken and that they would be best treated with non-pharmaceutical methods.

There’s also disagreement about whether the current drugs in development are safe and effective. The research on non-pharmaceutical treatments shows that cognitive-behavioral therapy and mindfulness may be more effective than flibanserin and have no side effects, but because they’re not backed by pharmaceutical industry funding, the sample sizes are miniscule compared to drug clinical trials. This lopsidedness does nothing to help answer the real question: what’s the best way to help women who are dealing with this problem?

The Viagra Effect

The most well-known drug for a sexual problem is of course Viagra, approved by the FDA in 1998. Viagra treats problems with physical arousal by allowing the penis to fill with blood and become erect. It’s a household name and has made billions of dollars for Pfizer, the company that owns it. Since Viagra’s approval, pharmaceutical companies have tried to develop a drug for sexual dysfunction in women. As psychologist and author Frederick Toates put it, there is “enormous commercial pressure to develop something treating it.”

In men, the most common sexual dysfunction is premature ejaculation followed by erectile dysfunction. In women, it’s low desire disorder, but it’s hard to pin down how prevalent this is. Different studies have found different percentages because they vary in how they defined low desire and how they asked women about it. One of the largest studies in the U.S., of 31,000 women in 2008, found roughly 10% with low sexual desire that they found distressing, which would translate to about 10 million American women.

Men also experience low desire that is considered distressing, but fewer of them. In a study of 570 Australian men ages 18–65, only 3% had low desire on its own without other sexual dysfunctions, and in a study of over 5,000 men ages 18–75 from Portugal, Croatia, and Norway, only 7% had low desire on its own. (There’s a reason for the gender-binary language: there has been virtually no research on sexual dysfunction in people who identify as non-binary or trans.)

Drugs for low sexual desire in women are often described as “female Viagra,” partly because it’s an easy way to place them in a category people are familiar with. But these drugs don’t act on the genitals like Viagra and they don’t treat the same problem. Currently, there is no drug for men to increase their desire.

One of the largest studies in the U.S. found roughly 10% of women surveyed had low sexual desire that they found distressing.

A drug that worked on the genitals wouldn’t help much for low sexual desire disorder, because in women, physical arousal only overlaps about 10% of the time with feeling interested in sex. No one knows why, but women’s genitals become aroused when women watch a wide variety of things, even when their subjective feeling about what they’re seeing is blasé or even negative. In an experiment, women reported feeling less aroused by an erotic film shot from a male point of view and more aroused by one shot from a female point of view, but they had the same physical genital response to both. Even in men, physical genital arousal overlaps with feeling aroused only about half of the time.

Drugs to treat low desire need to focus on the brain, and that’s not easy. Both women and men can be thought of as having a sexual gas pedal and a sexual brake pedal in the brain, according to researchers at the Kinsey Institute. The gas turns on in response to sexually exciting stimuli. The brake turns on in response to threats and stress. Women’s brakes are more sensitive than men’s to factors like stress, anxiety, lack of trust, relationship issues, body image, and trauma history. Some of these may not even be possible to control with drugs. Women’s sexual desire dysfunction is “almost always about too much activation to the brake,” says Emily Nagoski, who wrote the recent book Come As You Are: The Surprising New Science That Will Transform Your Sex Life .

One thing that can press on the brakes is feeling like there’s something wrong with you sexually—say, feeling like the way you experience desire is deficient. This is more common than it needs to be, because most people don’t know that there are two kinds of sexual desire and that both are normal.

Spontaneous desire feels like it comes out of nowhere. If you are sitting on the couch and suddenly, for no immediate reason you’re conscious of, you want sex, you’re experiencing spontaneous desire. Responsive desire feels like it happens in response to some external stimulus. If you’re sitting on the couch, your partner kisses you, and then you start to want sex, you’re experiencing responsive desire. What Barbara experienced when she didn’t desire sex until it was happening? That’s responsive desire, too. A person can have spontaneous desire some of the time and responsive desire some of the time, or spontaneous desire when they’re younger and responsive desire later in life.

Many more women than men have primarily responsive desire—about a third of women compared to only 3% of men, according to studies in 2003 and 2007. Based on the prevalence of responsive desire in women, many sex researchers and sex educators argue that most cases of “low sexual desire dysfunction” are only dysfunctional if we assume that women are supposed to have spontaneous desire.

The Trials

Back in 2011, Barbara told me, she picked up the phone and enrolled in the clinical trial for flibanserin that she’d seen advertised. It was a blind trial. She felt anxious driving to her intake visit, where the doctors did a physical exam and an EKG test, but she had no anxiety about the trial after that. “I really, really, really wanted this to work,” she says. But she didn’t feel any increase in desire.

Eventually, her husband Greg noticed Barbara was keeping records every day—she had to keep track of her responses to the treatment, like how many “satisfying sexual encounters” she’d had. Halfway through the trial, he asked what the records were about. That was the first time she talked to him about her low sexual desire.

A few weeks or months after Barbara told Greg about the flibanserin trial and her low desire, Boehringer Ingelheim decided they had enough information and stopped the trial. Barbara, it turned out, had been on the placebo. As is common in clinical trials once the company decides they have enough information to believe the drug is working, they offered everyone on the placebo a chance at the real thing.

She jumped at the chance to try flibanserin—this time, not in a blind study, because she knew she was getting the drug. “My sexual desire came back in full swing,” she says. “It changed everything about me.” She started to initiate sex more often. “It made my husband very happy.” She experienced no side effects. But her response was, in fact, unusual.

As the background report for the FDA advisory committee states, about 8,000 women with low sexual desire have taken flibanserin in clinical trials. In Phase III clinical trials, flibanserin did not show a statistically significant difference compared to the placebo in sexual desire as self-reported in a daily diary. On top of that, 15% of patients on flibanserin stopped treatment during the trial because of a side effect—most often dizziness, nausea, fatigue, and sleepiness—compared to 7% of patients on the placebo. Patients tolerated flibanserin less well if they were on common prescription drugs, including SSRIs and hormonal contraception, or if they drank alcohol. In the trial combining flibanserin with alcohol consumption, three out of 47 women developed a serious side effect of fainting or low blood pressure requiring medical attention.

However, flibanserin did perform significantly better than the placebo when women reported sexual desire on a monthly basis: on a 100-point scale, women on flibanserin gained an extra 6.25 points of desire. The trials also measured frequency of sexually satisfying events, or SSEs. Women on flibanserin had, on average, 0.8 more SSEs per month than women on the placebo: 4.5 satisfying events for flibanserin versus 3.7 for the placebo. In addition, a small percentage of women appeared to respond more positively, the way Barbara did. Controlling based on the placebo group’s response, about 10% of women got a boost of four or more SSEs per month due to flibanserin.

Barbara was only on flibanserin for about two weeks. Boehringer Ingelheim dropped the drug in 2010 because the FDA advisory committee had voted against approving it.

When Barbara heard she’d be taken off of flibanserin, she was very upset. The doctor who had presided over Barbara’s flibanserin clinical trial was Dr. Irwin Goldstein, the director of the Institute for Sexual Medicine in San Diego. “Dr. Goldstein was there when I found out that they pulled it,” she recalls. “He said, ‘Can I interview you right now?’ ” He recorded her reaction to the news right there in his office. “He took that to Cindy Whitehead at Sprout,” Barbara says. “Sprout picked it up and bought the rights to flibanserin and kept clinical trials going.”

Sprout Pharmaceuticals is a Raleigh, North Carolina-based company started by husband-and-wife team Cindy and Bob Whitehead. The Whiteheads bought the rights to flibanserin for an undisclosed sum in 2011. A July 2012 article in the Triangle Business Journal reported that Sprout had raised $25 million from April to July 2012 to invest in the drug.

Dr. Goldstein and his wife Sue Goldstein were at the FDA meeting along with Barbara. During the panel, Dr. Goldstein argued over and over again that FSIAD is an “unmet need” for drug development. The FDA has a special fast-tracked development process for drugs that they deem treat an unmet need, meaning that existing treatment options are not adequate.

One of Dr. Goldstein’s points was that we need drugs to treat FSIAD because only then will the medical system take it seriously as a condition and begin educating medical students about it. “The way this works is it all comes from the top down,” he said. If flibanserin were to be approved, he said, “there will be much more interest in everybody learning and understanding this drug. We will then have education in medical schools for women’s sexual health.” Doctors in the U.S. currently get only three to ten hours of education about sex during their four years of medical school.

Without a Pill

A plush, anatomically accurate vulva the size of a dinner plate sits across from Emily Nagoski’s desk in her office at Smith College. Nagoski, a sex educator and community wellness director at Smith College, says the idea of helping women with low desire is “ultimately nice and good. We have exactly the same goal in mind.” But, she adds, “for 15 years they’ve been looking for a drug. I’m pretty sure they’ll never find one.”

Nagoski was invited to a webinar hosted by Sprout on October 15, 2014. She talked to their publicist and also to Cara (not her real name) who, like Barbara, suffered from low desire and participated in one of the flibanserin trials. “She was so into the drug,” Nagoski says.

“She told me that she had experienced really severe fatigue” when she took flibanserin in the morning. “She couldn’t drive herself home. She had to take a sick day at work one day because it was so serious.” It’s why, in the next round of clinical trials, the FDA had clinicians test to see if the drug impaired people’s driving. “That’s not an OK risk, to increase your sexual desire or satisfaction by this little amount and risk people dying in traffic accidents. Not a good balance of risk and benefit.”

Nagoski asked Cara if she experienced pleasure, to which Cara replied, “Yes, I have orgasm.” Nagoski thinks that Cara’s responsive desire is intact and that she does not have a medical dysfunction, but is simply unaware that responsive desire is normal. On the phone, she explained responsive desire to Cara and, at Cara’s request, promised to send her a copy of her book, Come As You Are . She says she wrote it basically to tell women that there’s nothing wrong with them—that the science of sex research says they’re normal. Cognitive behavioral therapy and mindfulness work to treat low desire, she says. “But there’s no profit motive in promoting those.”

As Lori Brotto, a psychologist and women’s sexual health researcher at University of British Columbia, says of women’s sexual dysfunction, it’s “a lot of science mixed with a lot of politics mixed with, some might even argue, hidden agendas, and it’s hard to sift through it all.”

Flibanserin works on neurotrasmitters in the brain “by increasing dopamine and norepinephrine (both responsible for sexual excitement) and decreasing serotonin (responsible for sexual inhibition),” according to the Sprout website. It’s designed to be taken every day, unlike Viagra which is designed for men to take on an as-needed basis before they have sex.

“There’s no profit motive in promoting therapy or mindfulness.”

Dr. Goldmeier, the British sexual health clinician, says flibanserin “probably showed some efficacy. Probably it’s actually safe.” The problem, he says, was “the placebo response rate is so high…You have problems showing it was better than the placebo.”

Flibanserin was only better than the placebo on some metrics. On the one hand, the difference of 0.8 sexually satisfying events per month was statistically significant, and patients—at least those who spoke at the FDA meeting—said they found it meaningful. On the other hand, women in the clinical trials also kept a daily electronic diary—the diary Greg saw Barbara recording—in which they recorded their most intense level of sexual desire that day, on a scale from zero to three, and the diary sexual desire scores were not significantly different between women on flibanserin and women on the placebo. Given those two apparently contradictory findings, is the drug worth the associated risks? Is it better than any other available treatment for FSIAD?

Some experts don’t see the side effects as deal breakers. “Quite honestly, I think way too much is being made about this whole issue,” says Dr. Cindy Meston, a sexual psychophysiologist at the University of Texas at Austin and a member of the advisory board of S1 Biopharma Inc. “Get real. The FDA approves so many drugs that are not all that safe.”

Pharmaceutical companies have certainly been doing all they can to sway the FDA towards approval. One obvious example of this is Even the Score, a website that supports drug approval and frames the FDA as sexist for denying approval. Even the Score is partially supported by Sprout and by the pharmaceutical companies Trimel and Palatin.

“On certain outcome measures they keep failing, and on other outcome measures, which they’ve helped design, they can win,” says Moynihan, the author. “That, I think, is one of the major pushes of Even the Score: to get the FDA to change the way it measures success in trials.”

For low desire, studies show that non-drug treatments are effective, including sex therapy, cognitive-behavioral therapy (CBT), and mindfulness therapy. There are several reasons these studies have much smaller sample sizes than the average pharmaceutical study: the challenge of finding people willing and able to commit to a regular therapy session for the duration of the study, the need for trained sex educators or therapists to run each group, and just the lack of pharmaceutical industry funding.

One of the earliest controlled studies, in 2001, found CBT to be effective at decreasing the symptoms of low desire disorder in women. Before treatment, about 60% of the women in the study reported believing each of the following sexual myths: men are always ready to have sex, and sex shouldn’t be planned. Roughly a third of the women believed each of these three sexual myths: sex should always end in orgasm, couples shouldn’t have too much or too little sex, and you can’t have sex if a man doesn’t have an erection.

“The FDA approves so many drugs that are not all that safe.”

The treatment was three months long and consisted of a weekly two-hour sex therapy group for couples with homework assignments. After treatment, the percentage of women in the treatment group with all six criteria for low desire disorder decreased from 100% to 26%. The percentage of women who said they had no symptoms increased from zero to 28%. Participants, both men and women, judged all the techniques they were taught to be useful, especially the sensate focus and communication skills.

More recently, a few studies have found mindfulness, cognitive therapy, and education effective. One in particular, run by Lori Brotto and Rosemary Basson, studied the effects of these three in group therapy with 95 women: half received treatment consisting of a 90-minute group session once every two weeks for a total of four sessions. The other half, the control group, had their treatment delayed.

The four sessions included mindfulness meditation, the practice of nonjudgmentally paying attention to one’s feelings and sensations. The treatment sessions also included education about responsive desire and how mindfulness affects brain function, exercises in which participants noticed sensations from their bodies and genitals, looking at their own genitals with a mirror, and group discussions. Women were assigned homework of daily mindfulness practice and noticing their sexual beliefs and body image. When researchers followed up six months later, desire increased more in the treatment group while distress decreased in both groups about the same amount.

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But one issue with therapy and mindfulness treatments is that going to treatment regularly—even online—is more of a time commitment than taking a pill. People drop out, to the point where a 2013 study on the attrition from an internet-based treatment for FSD found that 23 of 40 people in the study dropped out. People who stopped had significantly lower relationship satisfaction and intimacy than those who stayed, so the study authors’ recommend the treatment for women with high relationship satisfaction and intimacy. But that doesn’t help those not in that category.

Dr. Goldmeier says mindfulness and cognitive-behavioral therapy are “not the quick fix that most people want.” Also, the studies present a problem. “There isn’t an actual placebo that you can have for mindfulness. Most of the control groups are waiting lists.”

Non-pharmaceutical treatments aren’t just for women, either. Dr. Goldmeier treats men in his own practice with mindfulness and, anecdotally, finds it effective. A combined analysis of many studies on men published in 2014 found that Viagra and psychosocial therapy together were more effective on sexual satisfaction than either were alone.

Third Time’s a Charm

On February 17, 2015, Sprout announced that they had resubmitted flibanserin to the FDA for approval, and on June 4, an FDA advisory committee voted 18-6 to recommend that the FDA approve flibanserin. All of the 18 who voted yes recommended approval with stronger risk management options than just labeling; none voted to approve the drug with labeling alone to describe the risks. Six of the 18 yes voters used the words “conflicted,” “uncomfortable,” “difficult,” or “on the fence” in describing their decision. One even went so far as to say “I applaud the people who voted” no.

The FDA approved flibanserin on August 18, and Sprout announced that it will market it under the name Addyi. Just two days later, the small company announced that they will be acquired by Valeant Pharmaceuticals for $1 billion. In a press release, the company said that Addyi will be available October 17, and as part of the risk management recommended by the FDA, will only be available through physicians and pharmacists who have been certified through a training process.

Perhaps it isn’t so much a question of whether we can develop drugs to affect low desire. Researchers have developed other drugs that affect the brain—Prozac, Zoloft, Ritalin—and it seems possible that they could develop a drug to affect desire in the brain, in some people, given enough time and money. But the question remains of whether drugs are the best way—if they’re reasonably effective, and if they offer a reasonable amount of benefit for a tolerable amount of risk.

Barbara, for her part, sees her low sexual desire as a dysfunction and a terrible one. FSIAD is “a very bad thing for a relationship,” she says. “You want to hug your partner, you want to be close to your partner, but you don’t want sex. And that’s screwed up. There’s something wrong there…And how do you think the partner feels? Totally shut down, like there’s something wrong with them.”

What Barbara describes as “screwed up” for her could easily be normal responsive desire for other women. Wanting to hug, snuggle, or kiss a partner without wanting to have sex at the moment is perfectly fine. What would it be like for Barbara if she knew that responsive desire is normal? It might not be a magic bullet, but it’s hard to believe it’s not at least a starting place.

Photo credit: Sprout Pharmaceuticals

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