The Big O A new pill promises to increase female libido. One drag-racing, fire-spinning sex researcher believes there is a better way to satisfy women.

In the late ’90s, when Nicole Prause started her predoctoral work in psychological and brain sciences at the Kinsey Institute, a center at Indiana University for the advancement of sexual knowledge, the atmosphere was one of charged possibility. Viagra had just been approved, and within months the clinic had changed almost beyond recognition. With the pop of a tiny pill, erectile dysfunction — previously one of the largest sexual complaints among men — had all but vanished. Prause recently recalled, “When we did see it, it was a matter of the guy had been with his girlfriend for six months and last night couldn’t get hard a second time. So he thought he had ‘erectile dysfunction.’ The threshold had clearly changed.” The sexuality research community was cautiously optimistic: If a solution to men’s sexual woes was but a prescription away, could a female equivalent be far behind? Prause’s adviser, Erick Janssen, had been retained as a consultant by a pharmaceutical company, and he offered her a chance to be involved in a pioneering clinical trial for a prototype they hoped would become the Viagra for women. Prause became the drug trial’s lab coordinator. She would help with the technicalities of measuring female arousal — she and Janssen had just written a prominent work on the topic and had been enlisted for precisely this expertise — and she would provide feedback to the company on how its approach played out. Prause remembers well the meeting in Marina del Rey. It was her chance to share her experience with the rest of the team and, she hoped, to help the company improve its chances of success. They were flying her out, putting her up in a hotel — a rare prospect for a grad student. Prause pictured herself explaining that the company’s strategy was rooted in the unfounded assumption that arousal for women was the same as arousal for men: blood flow to the genitals. She hoped to persuade them to take a different approach, or at the very least to use a better system of measurement than vaginal pulse amplitude, which proponents claimed measured this blood flow but which she and Janssen had shown was deeply unreliable. Prause’s first surprise: She wasn’t just the youngest person present, she was also the only female. Her second: No one expected her to say a single word, let alone share any expertise. Instead, the usually brash 23-year-old found herself sidelined as the men around her made definitive statements on what women wanted and needed. “They won’t want to do this, they can’t do that,” she remembers them saying. “I remember thinking, Well, how do you know this, and how can you be so sure?” Among the topics never mentioned were attraction to sexual partner, marital satisfaction, or any number of metrics that have repeatedly been tied, for women, to a satisfying sex life. Later, at a conference, Prause expressed her frustration to a friend who worked as an adviser to another pharmaceutical company then testing its own drug. He laughed. Her story was benign in his experience. He’d had a meeting where the scientists were urged not to make the drug too effective, lest it turn women into nymphomaniacs and jezebels. “It was my first taste of pharma,” Prause recalls. “And I said, ‘Never again.’”

Prause is tall and lean, with the physique of a competitive long-distance runner (she trains every day, often more than once), blond hair that frames an angular face, and intense blue eyes. At 37, she has multiple scars on her arms and legs — ­remnants of drag-racing crashes and close calls from one of her newer pastimes, fire spinning, a lethal-looking combination of lit batons and acrobatics that is illegal in some states. Even growing up in a conservative family in Beaumont, Texas, Prause was never one to blend in. “For someone to say I was normal would’ve been horrific to me as a kid,” she says, smiling. It was this iconoclastic streak that drew her to Kinsey in the first place. She has always found herself attracted to topics, like sex, that others want to avoid. Prause is not easily deterred: The spring before last she totaled her motorcycle on a racetrack (“I have a bit of a problem with speed,” she shrugs), breaking two ribs and leaving her scapula in seven pieces. For more than a year she was unable to ride; she couldn’t grip the handlebars. But a few months ago, bones mostly healed, she decided to get back on and purchased a brand-new model to replace the old. It’s this sort of blithe confidence that has enabled her to flourish in a field where little has changed, fundamentally, since those early days of failed pharmaceutical trials. There have been a few undeniable advances. The conversation, for one, is slowly shifting. When William Masters and Virginia Johnson first spoke in the ’50s about sexual responsiveness, pioneering some of the earliest laboratory measurements of arousal, they were met with skepticism and censure. Now a TV series about them, Masters of Sex, airs on Showtime. Topics that were once taboo are now open to discussion. (Though not always: Prause’s stepmother, she recently found out, tells friends her stepdaughter is a rape counselor rather than reveal her true title, sexual psychophysiologist. Prause explains it away with a nonchalant wave. “We’re from Beaumont. All four of my sisters had debutante balls.”) Research has also begun to shift focus. No company is still trying to make a female Viagra that functions by increasing blood flow to the vagina. Even theoretically, the data have never supported this approach. For men, physical arousal and self-reported desire largely go hand in hand. For women, it’s hard to be as precise. Some researchers see arousal as the overall category and desire as one of its components. Others think the two are completely separate, that a body can be aroused without a woman feeling like having sex. Either way, after multiple failed trials and billions of wasted dollars, the industry seems to have finally caught on to the reality that, for women, desire is as much psychological as physiological. Addyi (flibanserin), the first drug approved by the FDA to treat low sexual desire in women, targets the mental parts of the equation — the brain regions responsible for reward and pleasure — by acting on levels of serotonin. Developed by Sprout Pharmaceuticals and set to be released October 17, it was originally conceived as an antidepressant until researchers noticed that it came with a positive side effect on sex. But, as with many antidepressants, the exact mechanism of action remains unclear. Worse, the drug doesn’t seem to be particularly effective. It results in an average increase of between one-half and one satisfying sexual event a month, but it doesn’t change self-reported sex drive. It also has worrying side effects, like a fall in blood pressure and loss of consciousness, and it’s contraindicated for anyone planning on consuming alcohol at basically any point. “All the data I’ve seen make it look like a significant but very weak effect,” an early consultant on the drug, Barry Komisaruk, told me. “It becomes a personal choice: Are all of these costs and side effects worth it … especially for a drug that is minimally effective in the first place?” Still, its release is a sign of at least some progress for pharmaceutical researchers who have spent the last decade fruitlessly testing dopaminergic drugs (a class that includes cocaine and methamphetamines and that comes with a high risk of addiction) and testosterone (which carries large cardiovascular risks at an effective dosage). It doesn’t help that research into sexuality continues to be marginalized. Prause’s graduate adviser warned her early on how hard it is to receive grants. (Prause, naturally, took this as a challenge to be overcome. “I would just do it better than anyone else,” she says.) But funding is still scarce, and so experimental data are limited. To date there has been only one large randomized controlled psychological trial looking at female desire, which took place in Canada and used cognitive behavioral therapy. Drug research has fared slightly better. The most famous example: a French trial for a melanin appetite suppressor, bremelanotide, which went by the nickname the “Barbie drug.” Get tan, lose weight, increase sex drive. Despite being halted in the past for safety concerns, the drug is now in Phase 3 trials. “Currently there are a couple dozen drugs to treat male sexual problems,” Prause points out. Addyi is the first for women, but it doesn’t even address the true culprit. In daily diaries, women document no change at all in desire. “And low drive is still the most common sexual problem women report.” Despite the initial promise of the ’90s, there has been no quick fix to revolutionize female sexuality the way Viagra did for men. The measurement problems Prause and Janssen originally identified remain as problematic as ever. How do you even measure desire? Certainly not by inserting a reflective tube to measure vaginal pulse amplitude, which is still the preferred method of labs and companies alike, despite multiple papers pointing out its lack of validity. Nor by questionnaires that purport to measure level of sexual function with questions like “I find myself thinking about sex while at work” and “I think about sex more than I would like to,” which lack reliability and tend to internalize societal values. (What’s “more,” exactly? Is thinking about sex at work a problem?) Going by those flawed criteria, Prause freely admits she is a sex addict. But to develop new measurements, you need more experimental data, and for that you need a willingness to stake your career on an area that remains largely stigmatized. “The number of people doing sex and neuroscience you can count on two hands,” Prause says. “You only need one hand to find those who actually measure physiological changes in genitalia.” There hasn’t even been a reliable population-level study of the prevalence of sexual dysfunction in women. It’s a problem whose true scope, let alone solution, remains unknown. “I’m looking at existing marketing, at the overpromise of Addyi, and thinking, This is not the only option women should have. It pisses me off,” Prause says. “Women are getting a raw deal. If I don’t do this, it will be a long time before anyone does.”

When we first meet at a café in Los Angeles, Prause is lugging a battered wheeled trunk behind her. Though Prause has been a research scientist at UCLA since 2012, she is in the process of setting up her new lab at Liberos, a company she founded earlier this year to address what she feels is the woefully inadequate state of research into sexuality broadly, and women’s sexuality in particular. The Liberos tag line: the freedom to desire. While Liberos is part of UCLA ’s startup program and remains affiliated with the school, Prause has just given up her official lab. In late 2013, she found herself embroiled in a debate with the university’s Institutional Review Board over a study protocol that involved inducing orgasm. Previously she’d shown that she could effectively and safely study sexual arousal in the lab, and her work had received high praise from other researchers in the area. (Psychologist Meredith Chivers, the director of the Sexuality and Gender Laboratory at Queen’s University, told me that Prause is “one of the best sexual psychophysiologists in our field,” calling her work “theoretically grounded, empirically rigorous, and methodologically precise.”) But the reviewers questioned the importance of sexuality research that was too overtly, well, sexual. (When reached for comment, UCLA issued a generic statement about the review process.) The experiment was eventually approved at her collaborator’s institution, the University of Pittsburgh, and when Prause’s UCLA contract was complete, she decided to seek a friendlier environment. UCLA was, after all, the school that had turned down the option of holding a stake in what would eventually become Viagra. Prause systematically empties the contents of her trunk onto a table amid a lunch-hour crowd of onlookers who are equal parts curious and blasé: a laptop with ample amounts of pornography; several butt plugs; a Bluetooth-operated EEG headset that looks like a large spider and fits neatly over your skull, mimicking the touch of a skilled masseuse; and a sizable vibrator, along with genital attachments for both women and men. (A common question among the public is whether vibrators work for men. The answer, according to Greg Siegle, one of Prause’s collaborators at the University of Pittsburgh, is a resounding yes.) These are the main tools in Siegle and Prause’s latest series of studies, tools she uses to introduce sexual stimulation, at times inducing orgasm, in the lab in order to improve researchers’ ability to understand the physiological, neural, and psychological signs of desire and arousal. She hopes in turn to eventually use these indicators to treat a range of conditions, from hyposexuality — or lack of sexual desire — to depression. Much of the previous work on orgasm has relied on self-report: I am having an orgasm, or I’m not. One series of experiments led by Barry Komisaruk, for instance, depends on people pressing a button to signal they have experienced sexual release. In men, such self-report is fairly straightforward. It’s based on ejaculation. In women, however, it becomes trickier. How do you know you’re having an orgasm for sure? How do you know if what you’ve always thought of as orgasm is, in fact, that? The problem is not necessarily unique to women. One early study looked at what would happen if men were blocked from seeing their own erections: They became highly inaccurate in rating their physical arousal. For women, it doesn’t help that the popular press is rife with misinformation. Women cannot have an hourlong orgasm, Prause points out, despite what the latest magazine cover might have you believe. To “take away some of the mystery,” in Prause’s words, she relies on more precise measurements. An EEG headset is used to measure brain waves. (In another version, the EEG is replaced by f MRI .) Around the chest goes a respiration belt, and on the finger, a device to measure skin conductance. A tiny disc-shaped electrode that measures temperature — a thermistor — is placed on specific locations on the genitals. A modified butt plug fitted with a specialized pressure gauge is placed inside the anus to measure contractions. And then the “task” — “though it’s not really a task at this point,” Prause says — begins. First, participants watch pornography to see if they can successfully self-regulate, increasing or decreasing arousal as instructed. Next comes a classic reward task, a game in which each correct response earns the participant a certain amount of money, but in this case, money is replaced by seconds of vibrator activation. (The genital reward, Prause has found, prompts much more accurate and motivated behavior than dollar bills.) The game culminates in simple pleasure — orgasm — if the participant is able to attain it. Interestingly enough, people often are. “A lot of people were surprised it worked,” Prause says. “They walk in assuming some automated protocol wouldn’t be good.” Prause and Siegle were initially worried about noise. Their lab is next to one that runs studies with children. An English researcher who had previously studied orgasm in laboratory settings assured them that women are “generally quite quiet,” Prause says. But they found the opposite to be true. One woman, Prause remembers, started screaming and throwing objects across the room. “She had a very good time,” Prause laughs. “She wasn’t the only one who was vocal, but she was the only one who damaged equipment.” While the data from the study are still being analyzed, there’s one result that is immediately striking: the number of false positives. “At this point I’m convinced a lot of women think they’re having orgasms when they’re not,” Prause says. “It makes perfect sense to me. All a woman knows is that there’s some big explosion of pleasure. At what point do you say, ‘That’s it’?” (One irony: Of the participants who failed to identify an orgasm, one was a sex-advice columnist.) Prause, however, hopes to demystify the process. She is currently working on an at-home version of the contraction measurement device used in the lab — a physical sensor that tells a woman when, physiologically, she is experiencing orgasm. Women, she believes, will be keen to know. “They often ask: ‘How did I do, Doc?’ I think they’re really curious about all of this stuff, and it’s so hard to get information.” For Siegle, the implications of the experiment are slightly different. His primary research focus isn’t sex. It’s depression. For years he has been looking for a way to reliably create high emotional excitement in patients — a way of breaking through some of the destructive, ruminative thought patterns that pervade depression. Several years ago he expressed his frustration at a conference. Prause was in the audience. “Nikky walked up and said, ‘You’re in the wrong domain,’” he tells me. “‘You’re not jacking up emotions high enough to disrupt thinking. You have to use sexual stimulation.’” Siegle was cognizant of the link between depression and sexual desire — depressed patients often report lower desire, and in recovery sex drive is often one of the first things to bounce back — but it had never occurred to him to study a possible therapeutic connection. “I thought, We have to do this work.” The ultimate hope is that sexual stimulation might help in treating not only depression but also anxiety, ­obsessive-compulsive disorder, and other conditions characterized by obsessive thought patterns. Stimulation and its pinnacle, orgasm, could act as a short circuit for thought, bringing the brain offline for a moment, like a reset button. Already some researchers have found that brain waves during orgasm mimic those during meditation, and Prause and Siegle’s initial results seem to confirm that finding. For both Prause and Siegle, the orgasm study is more proof of concept than anything else. They are gathering the data and laying the groundwork for an understanding of sexuality and arousal that could eventually lead to therapeutic advances: to help depression, in Siegle’s case, and to increase desire, in Prause’s. “Studying orgasm allows us to answer questions like, Is the pleasure system fundamentally not working in depressed people, or is it a matter of the threshold needed to activate it?” Siegle says. If it’s the latter, as he and Prause suspect, then possible therapies should focus on boosting the pleasure system. “It directly informs intervention,” Siegle says.