The Disease Monger's Tale
Addyi and the Demand That Wasn't There
Sildenafil, better known as Viagra, hit the U.S. market in March of 1998. By the end of April, physicians had written over 500,000 scrips. By March 1999, as sales passed $1 billion, the race for a “female Viagra” was well underway. But fifteen years later, when flibanserin (Addyi) limped across the finish line, its prize was 227 prescriptions in the first month and $10 million for the year. Despite tailwinds of falling stigma and rising medication use, annual sales have topped out at $90 million, about one-fiftieth of the erectile dysfunction market. Addyi was supposed to sell itself, but no one’s buying.
Development Hell
Back in 1999, German pharmaceutical giant Boehringer-Ingelheim thought flibanserin could be an antidepressant. But its mechanism, raising dopamine and lowering serotonin, is an odd fit for this class, so no one was surprised when four trials vs SSRI and placebo failed.
Boehringer-Ingelheim pivoted. As part of the trials, participants had filled out the Arizona Sexual Experience Scale (ASEX), a questionnaire designed to assess sexual side-effects of medications. Reviewing the data, none showed great outcomes for flibanserin. In fact, three of the four showed better results with the famously-bad-for-libido SSRIs. But one had a small boost in libido in women, enough to justify a new direction.
In 2002, they spun up two proof of concept trials. The studies recruited women with Hypoactive Sexual Desire Disorder, a DSM-IV diagnosis defined by “deficient or absent sexual fantasies and desire for sexual activity” and resulting distress. Investigators tracked ten measures, from the ASEX and Female Sexual Function Index to a monthly count of “Satisfying Sexual Events” and number of days with sexual thoughts. Flibanserin came out better than placebo on several.
Meanwhile, sildenafil and similar medications failed trial after trial in women. Apomorphine, a dopamine agonist derived from morphine, went nowhere. In 2004, the FDA rejected a testosterone patch, then a combination of testosterone and sildenafil.
Each null finding also killed a corresponding theory, because the supposed cause of women’s sexual problems changed with the treatment. Trials of Viagra-like drugs blamed a lack of genital blood flow. Testosterone-based drugs implied the issue was hormone levels. Flibanserin alters serotonin and dopamine activity, so it must be that “low sexual desire, or HSDD, stems from an imbalance of neurotransmitters in the brain.” As the sprint for a new drug turned into a slog, the explanations for female sexual dysfunction grew increasingly hand wavy.
By the mid-aughts, only flibanserin was still standing. For the next set of placebo-controlled trials, running 2004 to 2008, Boehringer-Ingelheim enrolled premenopausal women in long-term heterosexual relationships with HSDD. At baseline, participants reported 2.5 Satisfying Sexual Events (SSEs) per month. By study end, those on flibanserin reported 0.5 more SSEs each month along with a small increase on a daily desire scale.
Based on this data, flibanserin’s New Drug Application went before the FDA in 2010. The advisory panel rejected it, concluding 10-1 that the drug was ineffective and 11-0 that adverse effects outweighed any potential benefit.
The Summer Campaign
By 2012, Boehringer-Ingelheim washed their hands of flibanserin and sold the rights to Sprout Pharmaceutical. Sprout was a tiny firm based in North Carolina and owned by married couple Cindy and Robert Whitehead. Just two years earlier, the two had been running a different company, Slate Pharmaceutical. They dissolved Slate in 2010 after a warning letter from the FDA accused them of “grossly misleading marketing” tactics, such as implying that their implantable testosterone pellet could treat depression, erectile dysfunction, diabetes and HIV.
As a private company with little capital, Sprout couldn’t run more clinical trials. Instead, they pulled together more data and resubmitted flibanserin’s New Drug Application in 2013. The FDA rejected it once more, concluding that the treatment benefits, while statistically significant, were too small to outweigh risks like sedation and dizziness.
Sprout appealed the decision, and the FDA agreed to schedule a public advisory meeting on female sexual dysfunction for October 2014. That summer, Sprout funded a marketing campaign dubbed “Even the Score.” The score at issue was 26 to 0: the number of FDA approved sex drugs for men vs women.1 Marketing copy and news pieces cited a statistic that 43% of women suffered from sexual dysfunction.2 Sprout hired a former head of Women’s Health at the FDA to lobby feminist and medical groups. Their argument was explicit: rejecting flibanserin a third time would be tantamount to sexism.
At the October meeting, thirty attendees arrived on a bus with CEO Cindy Whitehead. Five of the eight panelists reported that Sprout paid their travel expenses. Before the committee, they spoke of their sexual difficulties, distress, and the value of treatment.
At this point, Sprout’s goal was convincing the FDA to allow endpoints focused on subjective desire and distress instead of Satisfying Sexual Events. SSEs had long been the standard outcome in this field, but Sprout argued this was a holdover from male-centric trials that defined success in terms of erection and penetration. After the meeting, the FDA agreed to drop the requirement and to replace the daily desire measure with a monthly questionnaire.3
These changes were critical to flibanserin’s FDA approval in August 2015. Within 48 hours of the announcement, Quebec-based Valeant Pharmaceutical purchased Sprout for $1 billion.
The Mantle of Feminism
Through all of this, Sprout and its allies cast their position as pro-woman and pro-sex, as per their tagline “women’s sexual health equity.” The phrase underscores their biggest talking point: not that Addyi was particularly effective, but that fairness demanded the drug be approved. At the FDA advisory meeting, one patient speaker stated:
“No amount of talk therapy is going to fix [this problem]. We can’t get better from a physiological need by talking about it. I would just be delighted if we had the same choices as men.” (FDA, 2014; 56-57)
Beyond the question of fairness, this argument smuggles in the assumption that these sexual difficulties are biological, and thus medical, in nature. In fact, calling low libido a symptom already begs the question. This didn’t go unnoticed, as the media split between articles accepting and doubting the medical frame, while academics argued whether the whole concept of female sexual dysfunction was an “abject example in corporate sponsored disease-creation.”
Critics also derided Sprout’s messaging as faux-feminism. For one thing, they pointed out that women’s pleasure received little attention in the proceedings. Neither trial results nor marketing claimed that Addyi made sex more enjoyable or orgasms more frequent, and women could interpret a “Satisfying Sexual Event” in various ways. One panelist noted:
“I would say something that would end up being pleasurable would be the fact that when it ends your husband doesn’t immediately think it was out of obligation.”
Another woman concurred:
“It is a success if he is having a good time…I might not even want to have sex but if he wants sex and then I give it to him then, yes, I was a good wife today.”
Their statements highlight the fact that, for reasons never stated, every clinical trial of flibanserin enrolled only women in long-term relationships with men. This is hard to square with the idea of Hypoactive Sexual Desire Disorder as a medical condition afflicting individual female patients.4
It’s also unusual since new drug studies want a “clean” study population, and the presence of male partners would seem to introduce many confounding variables. If increasing individual desire and sexual activity was the goal, then flibanserin could have been tested on single women. If increasing partnered sex was the goal, it could have been given to both partners. After all, most therapy for sexual issues assumes that the “problem” lies within the relationship dynamic, not one of the individuals.
Proxy Wars
Despite Sprout’s success at the FDA, the road ahead was rocky. In 2015, the prestigious JAMA published a meta-analysis that scrounged up three unpublished trials. Their data chipped away at the already small effects of flibanserin. Overall, the authors ranked the quality of flibanserin studies as “Very Low,” citing shifts in end-points, high dropout rates, and serious risk of publication bias. They concluded there was minimal evidence the drug works.
The public wasn’t enthusiastic either. In its first year, most prescriptions went unfilled, and Addyi’s underwhelming performance was all over the news. In November 2016, Sprout sued its parent company for “failing to commercialize” the drug. After two years, American doctors had written just 23,000 prescriptions. By November 2017, Valeant returned the drug rights to Sprout in exchange for dropping its lawsuit.
Since Sprout regained control, no further trials of Addyi occurred.5 However, a series of reviews and re-analyses popped up in academic journals. All four feature authors who are either employees or consultants for Sprout.
A 2018 review argued for a moderate effect (Cohen’s d 0.4) on desire.
A 2019 analysis pooled data to uncover a small effect (Cohen’s d 0.2) for increased Satisfying Sexual Events.
A 2021 article examined another endpoint, the Patient Global Impression of Improvement, to argue that flibanserin provides meaningful benefit.
A 2022 reanalysis examined the Female Sexual Function Index and found small improvements in desire, arousal, lubrication, orgasm, and satisfaction.
Sprout also stepped up its direct-to-consumer advertising but, in 2020, received an FDA warning letter for “false or misleading claims” about Addyi’s side-effects and scope of use.
More recently, things are looking up. An independent meta-analysis in 2024 concluded that flibanserin has small but real effects on sexual desire. Sales of Addyi tick up each year. A recent documentary describes its approval as “a pivotal moment in the ongoing struggle for complete health care equality, at a time when bodily autonomy hangs in the balance.” In 2025, Sprout won expanded approval for flibanserin’s use in post-menopausal women up to age 65.
Give the People What they Want
We assume that people have symptoms, go get diagnosed, then receive the indicated treatment. But sometimes people just want a drug because of its effect. Sildenafil and its ilk, like benzodiazepines and amphetamines, definitely do something, even though Erectile Dysfunction is just as made-up as Female Sexual Interest and Arousal Disorder. The diagnosis is incidental, somewhere between a rationalization and a cover story. Other times it’s the diagnosis that people are after, as a semblance of explanation, and the daily medication is there to keep yourself, and others, convinced. Sometimes people want both, or don’t know what they want, because people are often confused.
Flibanserin has so far failed because its makers were confused. They thought it was like Viagra, but it’s more like (yikes) buspirone. Sprout convinced the FDA, via intimations of sexism, to approve flibanserin. They tried to tell physicians, via iffy statistics, that flibanserin works. But they forgot to persuade regular women that they needed the drug. Treating female sexual dysfunction, if that’s a useful concept, will require a better acronym. It will also require a better value proposition: if not a drug that provides real benefit, at least a diagnosis that provides real meaning.
This counted different brandings as different drugs. At the time, only five distinct drugs were approved, all in the same class as sildenafil.
This statistic had been walked back by its authors (Laumann 1999).
It’s interesting to think why a drug company would want outcome measures likely to have larger placebo effects.
Addyi is one of those feminist milestones that principally benefits men.
For what it’s worth, there do not appear to be any RCTs of flibanserin not funded by a pharmaceutical company.
Maybe kisspeptin will do better (definitely has a better name) https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797718