Addyi’s Alcohol Safety Was Tested Mostly on Men

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If you happen to be a woman interested in taking Addyi, the first FDA-approved drug intended to treat low libido in women, your doctor will first tell you this: You absolutely cannot drink — at all — as long as you’re taking the drug, because alcohol has been shown to exacerbate its side effects, including fainting, dizziness, and low blood pressure. When the drug hits the market in mid-October, it will come with a black box underlining the importance of abstaining from alcohol while taking the medication.

But here’s the thing. Nobody actually even knows what would happen if a woman taking Addyi were to cheat and have, say, a glass of wine with dinner — because the research on the effects of drinking while on the medication was done almost entirely on men. The alcohol-safety study included 23 men, and a grand total of two women.

I’m like, Okay, but this is a drug for women. I don’t care how men react,said Dr. Jen Gunter, an OB/GYN in the Bay Area, who noticed this over the weekend when she decided to read through Addyi’s REMS, or risk evaluation mitigation strategy — basically, everything a medical provider must know before prescribing a drug to a patient. And the lack of women in the alcohol-interaction study is a problem, said Gunter, for a few reasons. For starters, there’s a good chance that patients will underestimate the seriousness of the alcohol warning. “People really, absolutely have to agree that they’re not going to have even a glass of alcohol,” Gunter said. “None of this winking at your doctor — Oh yeah, I can’t have alcohol, wink.”

And as Lori Brotto, a sex researcher at the University of British Columbia and a leading expert on low sexual arousal in women, points out, alcohol affects men and women very differently. Gender differences in the metabolism and toxicity of alcohol are well known, and women are more susceptible to toxicity effects than are men,” Brotto said in an email. “As such, I think the negative interactions between Addyi and alcohol found in the safety study are understated, and in women taking Addyi, I would expect the mixing to be more devastating.”

Because, as the results of the alcohol-interaction study showed, mixing alcohol and Addyi can result in some serious complications. Cindy Whitehead, the CEO for Sprout Pharmaceutical, told Science of Us that participants were instructed to take two to four shots of grain alcohol within ten minutes in the morning, and then take a dose of flibanserin (the drug’s nonbrand name), adding that the study was designed according to FDA guidelines for these sorts of safety tests. (Valeant Pharmaceuticals recently acquired Sprout for $1 billion, but Whitehead remains CEO of Sprout.)

The gender disparity, Whitehead explained, occurred because the experimenters found many more men than women who wanted to consume that much alcohol that quickly. (Which — really, they couldn’t find more than two women willing to knock back a few shots in the name of sex science?) The experiment itself is what’s known as a “challenge study,” which purposefully does not mimic real-life conditions, but instead is designed to demonstrate what could happen under extreme circumstances. In this case, what happened was this: Many of the study volunteers experienced fainting and dangerously low blood pressure; in some cases medical intervention was needed. Hence, the alcohol restriction. 

Whitehead also said that the company does plan to conduct experiments involving women and more true-to-life scenarios involving drinking; according to Nature, the FDA has required the pharmaceutical company to carry out three more studies on what happens when Addyi and alcohol mix. But this is, at least in part, an issue that goes beyond Addyi and alcohol. “Generally, women remain underrepresented in biomedical research,” write a trio of physicians in an editorial published in Nature in 2010. For example, an analysis of 56 studies published in nine of the biggest medical journals in 2009 found that just 37 percent of the participants involved in those studies were women. This problem persists, write the authors of the Nature editorial, despite the 2001 passing of the NIH Revitalization Act, which was intended to help balance that lopsidedness by increasing the number of women and minorities recruited for clinical trials. One of the usual reasons given for researchers’ tendency to use more men than women in their studies is that when you include women, you have to account for menstrual cycles or potential pregnancies, which can disrupt the data on the drug being tested.

And that makes sense, sort of — but less so when it comes to a drug that is explicitly intended for women. “If you have a drug that’s only for women, there’s no point in testing it in men,” Gunter said. “I just don’t see how safety data on 23 men is relevant.” Also, the men typically recruited for these sorts of studies tend to be young and healthy, Gunter added. “So if really fit men can’t handle it — well, I understand now why women can’t have alcohol, ever” while on the drug, she said.

The irony here, of course, is that for many women, alcohol itself works as an aphrodisiac. And, as you may recall, Addyi’s benefits are modest at best, with women in clinical trials reporting about one additional “satisfying sexual event” per month while taking the daily medication compared to women taking a placebo. Furthermore, some argue that the idea behind Addyi is inherently flawed, in that it is intended to increase spontaneous desire — the kind of sexual urge that hits you like a lightning bolt, out of nowhere — which essentially overlooks the fact that for many women, that’s not how the libido works, anyway. Surely a few women really will benefit from the drug, Brotto has said, but the matter of the potentially scary side effects of mixing it with alcohol likely “means that the market for Addyi will be even smaller than once thought.”