The Quest for Lust

Victoria felt her once-robust lust for her husband start to wane when she was in her early 30s, though she chalked it up to life circumstances—she was a busy mother of three young children. But after her fourth child was born, when she was 34, her yearning for sex flatlined permanently. She was bereft. Surely, she thought, there was something wrong with her.

Five years later, on an autumn day in 2014, Victoria stood before a packed public hearing at the FDA's White Oak Campus in Silver Spring, Maryland, and described in frank detail what it felt like to have her libido vanish. "I found myself avoiding any situations where a sexual experience might occur," she said. "For example, I'd go to bed after my husband fell asleep or jump out of bed in the morning before he got up so he wouldn't try to initiate sex. I even found myself avoiding simple hugs and kisses."

The worst was when the couple went on vacation to Mexico without their kids. "My mother joked, 'Don't get pregnant,' when we left. Unfortunately, my symptoms stayed the same. In a beautiful place with the man I love, my body was like a shell with nothing inside. My desire was still gone. This was devastating to both of us."

The FDA hearing in 2014 was a forum for patients, advocates, and health-care providers to talk about female sexual dysfunction—a condition estimated to affect 10 to 40 percent of adult women and for which there are few effective treatment options. One after another, women described the dimming of their libidos and the anguish it provoked: anxiety at the mere thought of sex, grief over their inability to enjoy what they once did heartily, shame and embarrassment about something so essential having gone awry, disconnection from their bodies, and injury to their relationships. Although it was never mentioned by name, a subtext of the hearing was the FDA's upcoming regulatory review of flibanserin, a failed antidepressant that an upstart drug developer, Sprout Pharmaceuticals, was trying to advance as a treatment for women with chronic low desire.

Commonly dubbed the "female Viagra," flibanserin has been embroiled in controversy, limned by two antagonistic camps that represent opposing views of the nature of female sexuality. On one side is what might be called Team Biology—scientists of various stripes who think that desire is a central nervous system mechanism that can be ratcheted up by targeting the brain. Indeed, the term "female Viagra" was always a mischaracterization: Erectile dysfunction drugs such as Viagra offer an easy vascular fix to a mechanical problem, literally giving physical arousal a boost when desire is already present. Similar drugs tested on women show that engorging their genitalia with blood does nothing to actually induce a longing for sex. Rather, what Team Biology wants—and what flibanserin does by decreasing serotonin and increasing dopamine—is to alter the levels of the neurotransmitters believed to inhibit and ignite desire, respectively.

On the other side of the debate is the proverbial Team Psyche, an assortment of social scientists who maintain that desire is a subjective experience, resistant to measurement, and contingent on an array of social, emotional, and contextual factors. To the degree that a woman feels her libido is lacking, Team Psyche says it could be due to stress, anxiety, a history of trauma, poor body image, relationship problems, or just plain old monogamy—research shows that for women, each month of monogamous commitment is associated with a slight but steady decrease in desire. In contrast, for men, it holds more steady. Low libido might cause women distress, Team Psyche concedes, but it isn't necessarily a disorder and may be a cultural creation, evidence of a media-fueled expectation that women constantly yearn to hop into bed, and the pharmaceutical industry's rush to pathologize—and profit from—a condition that's variable and natural. As Leonore Tiefer, a psychologist and an outspoken critic of the medicalization of women's sexuality, said at the hearing: "There is no 'normal' that you lost."

Team Biology won the flibanserin battle, at least on the surface. Amid a slick advertising campaign and investor anticipation of a billion-dollar market, the medicine was approved in 2015 as a treatment for women with chronic low desire. The drug was a flop. Sold under the name Addyi, only 4,000 prescriptions were written in its first six months, a meager total compared with the 300,000 written for Viagra each week after its launch. Sales last year totaled around $10 million, a paltry amount for a hotly anticipated new drug. Last fall, investors in Sprout Pharmaceuticals sued Valeant, claiming the pharmaceutical giant that acquired it for $1 billion after flibanserin was approved had failed to adequately market what they had believed to be their neurochemical gold mine.

In the aftermath of the drug's spectacular fizzle, both sides essentially retreated to their corners and continued in their separate quests to address flagging female desire. For some, the drug's lackluster market performance has brought a more fundamental question to the fore: How do you alter or fix something that's not fully understood in the first place? Kim Wallen, a psychologist and neuroendocrinologist who studies the intersection of hormones, sex, and social context at the Yerkes National Primate Research Center at Emory University, notes that the two sides are often portrayed as one that thinks a magic pill to conjure female lust is on the horizon and another that thinks there's no magic pill and never will be. But it's far more complicated than that.

"Desire in general is a really difficult topic. We think of desire as a craving for something we're lacking, like hunger for food. Sexual desire doesn't really fit into that model at all. It's necessary to understand what desire is before you come up with treatments."

Wallen compares the opposing sides to the parable of six blind men touching an elephant. Each thinks the section of the animal near his hand represents the creature's totality and remains not only oblivious to the big picture, but also biased toward his limited perspective. "In relation to sexual desire, I think everyone is seeing part of the same thing," he says. "It's just that they view it as the whole thing."

Low desire is a relatively recent addition to the annals of human suffering. In 1966, Masters and Johnson put forth their seminal theory of human sexual response, neatly graphing how arousal leads to orgasm and operates essentially the same in men and women. In the late 1970s, psychiatrist and sex therapist Helen Singer Kaplan offered an alternative model in which desire is a distinct phase that precedes arousal. Around the same time, psychoanalyst Harold Lief argued that low desire is an ailment independent of other problems with sexual function, like inability to orgasm. Kaplan's and Lief's ideas led, in 1980, to what eventually became known in the Diagnostic and Statistical Manual of Mental Disorders as hypoactive sexual desire disorder, or HSDD. Within a few years, it was the most prevalent sexual complaint of women in America.

Little in the way of treatment was available for this newly identified problem, and feminist critics claimed that the very diagnosis was flawed because it was based on an erroneous assumption that women's sexuality operates the same way as men's. In 2002, Rosemary Basson, a psychiatrist at the University of British Columbia, put forth a different and more complex model of female desire, one that posits that women's desire is responsive rather than spontaneous. In Basson's view, women typically don't have a free-floating craving for sex; rather, it's inherently contextual, a response to getting turned on by external stimuli or a longing for something other than immediate physical gratification, such as emotional closeness, a fulfillment of duty—even just wanting to want.

Basson's framework suggested that researchers should think more broadly about women's motivation for sexual activity—and motivation, Wallen says, is a key to understanding desire that was overlooked in earlier sex research.

For some, thinking about the motivation for sexual activity leads naturally to the brain. Jim Pfaus is a psychologist and neurobiologist at Concordia University and one of the most prominent torchbearers of the so-called "vagina-brain connection." A brash ex-punk rocker, Pfaus examines the way minute manipulations of neurochemistry affect the sexual behavior of rats. In one study, he blocked female rats' ability to reap opioid rewards during copulation and found that even when their reward system was later unblocked, they rejected mating efforts, suggesting that bad sex leads to an expectation of more bad sex in the future. In other studies, Pfaus has shown that when given drugs that activate dopamine—the neurotransmitter that mediates the brain's reward and pleasure systems—female rats become rabidly, proactively sexual. And because rats and humans are biologically similar in some ways, he suspects that when women don't respond to compounds that send female rats into a libidnous frenzy, it's because their minds are somehow holding them back. "In a way, I think female rats are teaching us something about female desire," Pfaus says. "When they have it, it's big, and they are completely in charge of it. There are pharmacological mechanisms that show in an unambiguous way that they want to have sex. But I think we've beaten that out of women in Western culture."

Others counter that social, emotional, and environmental factors are precisely what make or break human sexuality—that if a woman can't stop thinking about the household chores or feels unattractive or just can't stand her partner's breath, well, those thoughts and feelings are the very basis of lack of desire. As Alessandra Hirsch, now a medical student, testified at the 2014 FDA hearing, "Here are some things that have helped me with periods of low libido: My boyfriend, 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 showerhead, tips from my girlfriends, back rubs, back scratches, a good night's sleep, an absence of judgment from my boyfriend, an absence of judgment from my friends, a defiance of judgment from society, and an acceptance of myself and the libido I came with."

It's a list that Lori Brotto, a psychologist and sex researcher at the University of British Columbia, might cite as evidence that desire is rooted in one's mental state. Since 2002, Brotto has been involved in treating women with therapy based on mindfulness, the practice of nonjudgmental awareness rooted in Buddhism. She teaches women concrete skills of body awareness and present-moment focus, and then helps them gradually apply those skills to sexual settings. Her theory is that sexual response in women is related to the mind being in sync with the body, an idea supported by many studies that show that women experience low sexual concordance, or a disconnect between physical and subjective arousal. "Becoming more aware of the body, noticing the body nonjudgmentally, can be a way to really tune into arousal," she says. Furthermore, she adds, "When women pay attention to and identify the triggers, context, and the kind of stimuli that elicit sexual desire, suddenly they're in a position where they feel empowered to make changes within their environment and within their relationship that might increase desire."

Pfaus and Brotto can seem like foils, dueling emissaries of Team Biology and Team Psyche. In some ways, they are. Yet there are areas where their views overlap. Pfaus remains an adamant defender of flibanserin and is now at the forefront of testing another experimental drug for low desire. Called bremelanotide, it's a synthetic peptide that primarily activates dopamine, which increases sexual excitation. Yet he doesn't claim that human desire occurs in a biological vacuum. Much of his research has to do with how context and experience affect sexual expression, and his defense of flibanserin is more a defense of a biological contribution to desire within a larger behavioral picture. "None of these drugs should ever be used alone without sex therapy, where you're learning about desire and your sexual landscape," he says. "They need to be adjuncts to therapy, rather than a therapeutic intervention on their own."

Likewise, there's general agreement between the two sides that the current measures of desire don't offer a clear picture of what women really experience—let alone what boosting desire feels like—and that without better markers, there can't be targeted treatments. Many studies of desire measure the number of sexually satisfying experiences, or SSEs, a woman has in a given period of time. As Pfaus points out, "The SSE is a real male thing—you have an erection and you put it in a hole somewhere and that's considered sexually satisfying." Sharon Parish, an internist at Weill Cornell Medicine, explains that the focus on sexual activity is a carryover from research on erectile dysfunction, which tallies "successful" sexual events, and agrees that it doesn't adequately capture women's experiences. "Women can tell you they have absolutely no interest in a sexual event but they get into it and get stimulated and have an orgasm, but that doesn't mean their desire in general is any better," Parish says.

The imperative to find better ways to measure desire comes back to the question of what exactly desire is, which itself evokes the complexity of women's sexuality. "What's really missing is good qualitative work that asks women themselves what they deem to be important indicators of improvement in sexuality," Brotto says. "Even if the primary concern is loss of desire, it may be that an overall increase in a satisfying sex life has nothing to do with desire for or frequency of sex. In my lab, we tend to have multiple different indicators not only of desire but of quality of life, mood, relationship satisfaction, and body image, and we try to tell a story based on that collective outcome." The division remains between those focused on the causes of sexual unhappiness and the clinical diagnosis itself, enforced by what Brotto describes as vastly different theoretical models. But, she says, "It would be lovely to find some sort of compromise or a system that allowed you to import elements of both."

Psychophysiologist Nicole Prause has done a lot of eyebrow-raising things in her effort to understand the nature of sexual desire and arousal. She's taken women's labial temperatures while they watch sexual films, hooked them up to vaginal photoplethysmographs to assess genital response to stimuli, showed them 3-D models of erect penises and asked them to rate their preferred size, and equipped them with vibrators and special anal plugs and instructed them to push a button at the point of orgasm. These days, the part of the body Prause is most focused on is the brain.

The former director of UCLA's Sexual Psychophysiology and Affective Neuroscience Laboratory, Prause left the post several years ago amid controversy about her sometimes unorthodox research methods and founded Liberos, a sexual technology start-up. The company's tiny Santa Monica office is a nest of computer monitors and wires, and Prause has lately been affixing electrodes to the heads of study participants and delivering transcranial magnetic stimulation, or TMS—pulses of low-voltage electric current to the brain—to see whether it affects desire.

In recent years, TMS has shown promise as a treatment for depression, and like depression, Prause thinks that desire is a central nervous system mechanism shaped by sensitivity to rewards. Just as someone with depression may experience a muted response to the pleasure of spending time with friends, eating a fine meal, or basking outside on a sunny day, with low sexual desire may not respond to, say, a sensual touch from a loved one. Something going on in her life echoes through the nervous system and mutes the response to rewards.

Bridging the psychological and physiological, Prause's work suggests a way of thinking about desire that surmounts the deep divisions around its origins. Prause thinks that under-reactivity to sexual reward is conditioned by social and emotional factors in a kind of feedback loop. "You have kids, you're tired for a long time, you get out of the habit," she says. "Sexual response is use it or lose it. We had a study where we looked at people who hadn't had an orgasm in a long time and didn't respond much sexually, and they said, 'It doesn't bother me.' If you've had a long period of not being responsive, the way TMS is thought to work—by resetting beta waves, weakening some neural connections, and strengthening others—may allow you to become more sexually responsive again. It's normalizing."

She is quick to clarify that electric brain stimulation isn't something that can, say, bring back the roaring sex drive a woman had in her 20s or renew the lust her partner's presence inspired in their relationship's early days. And no amount of neural tinkering, she says, can resolve the problem of simply being unattracted to someone. Pfaus calls the work "tantalizing," and speculates that brain stimulation may be yet "another way in" to resetting sexual response. "The more choices we have for women, the better we're able to tailor an intervention that works for them."

As for the enigma of lust, Wallen says, "There was a time in my career I thought we'd find a magic pill. The more I work, the more I realize that's unlikely because of this complex of variables. Mindfulness can have an effect, as can hormones, or just the awareness that you're taking a pill. There are so many avenues to altering desire."

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