Wait, Is Female Viagra Even Safe?

Let’s talk about the female Viagra, the drug that was once even more elusive than male birth control. American men with sexual dysfunction already have a number of drugs to choose from, while women with sexual dysfunction continue to battle a lopsided medical playing field. Research on a "little pink pill" for women has been ongoing for nearly 20 years, and yet this drug drought remains — until now.

One form of so-called female Viagra, flibanserin (market name Addyi), was approved by the FDA on Tuesday with help from Even the Score, a lobbyist group of various health and women's organizations seeking to close this gender gap in the drug market. But it turns out that advocating for gender equity in the form of a little pink pill is more controversial than one might think.

In June, an FDA advisory committee recommended agency approval of flibanserin — a major victory for the sexual health and pharmaceutical advocates who've been fighting to get the drug on the shelves over the last few years. It was the third time that the FDA took up flibanserin, having previously rejected it in 2010 and 2013. They'd cited various medical concerns, such as dizziness and fainting, low blood pressure, and negative reactions when mixed with alcohol.

FDA representative Andrea Fischer told Bustle earlier this month that the advisory committee held the meeting to discuss the benefits-to-risks ratio involved with flibanserin. After the committee overwhelmingly voted "yes" on recommending the drug for approval, it remained under review until Tuesday, when the FDA made the historic decision to approve it after five tumultuous years.

"It has been a remarkable journey to get to this breakthrough moment ... We celebrate what this approval means for all women who have long awaited a medical treatment option for this life impacting condition," said Cindy Whitehead, CEO of Sprout Pharmaceuticals, which manufactures the pill. On Wednesday, Sprout was purchased by Valeant Pharmaceuticals for $1 billion.

But as many celebrate flibanserin's FDA approval, there's a fledgling movement composed of hundreds of scientists and medical researchers still determined to block the drug from the market. To these researchers, it all boils down to the only thing we really want to know before popping the pill: Is the female Viagra safe?

Behind The Science Of Female Sexual Dysfunction

Male sexual dysfunction often gets national airtime — thank you, cheesy Cialis commercials — but what about female sexual dysfunction? It’s not a myth, a rarity, or an inconvenience. Hypoactive Sexual Dysfunction Disorder (HSDD), the most common type of female sexual dysfunction, is characterized by a persistent lack of desire for sexual activity, and is typically seen in pre- and post-menopausal women. The disorder is now listed under female sexual interest / arousal disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V).

Research provided by the FDA suggests that HSDD occurs more frequently in women than sexual dysfunction does in men. An FDA report released in October 2014 cites research showing that an estimated 43 percent of U.S. women between the ages of 18 and 59 experience symptoms of HSDD. There are currently no definitive causes of HSDD, nor are there pharmaceutical drugs available to treat the disorder — though HSDD Online points to several natural alternatives. These include Provestra and Femestril, which are billed as herbal "libido enhancements" for women.

Flibanserin will be the first pharmaceutical drug on the market tailored to pre-menopausal women with HSDD. Interestingly enough, the so-called female Viagra would work in the opposite way that actual Viagra does. Flibanserin alters certain chemical levels in the brain, while drugs for male sexual dysfunction simply increase blood flow to the genitals. That's because erectile dysfunction is all about, well, a lack of blood flow, while a woman's low sexual desire seems much more cerebral. As Dr. Mitra Boolel, a lead sex researcher at Pfizer, the company behind Viagra, told The Telegraph in 2004: "The brain is the crucial sexual organ in a woman."

There's also a big difference in administering flibanserin compared to Viagra and other erectile dysfunction drugs. Similarly to the birth control pill, women would have to take flibanserin every day — not just before getting busy in bed. (Though both Sprout and the FDA say that women should take the drug in the evening.)

The History Of "The Little Pink Pill"

Following years of clinical trials, flibanserin failed to make it through its first FDA advisory committee in 2010. Back then, the drug was being developed by German company Boehringer Ingelheim, and was initially tested as an anti-depressant. Medical articles on flibanserin's anti-depressant potential date back to the early 2000s, but the drug never panned out as planned. Instead, Boehringer researchers found that boosting chemicals like dopamine could possibly spark sexual desire.

While Boehringer reported in 2010 that its trial patients not only saw improvement in their sex lives, but also a "meaningful benefit" from the drug, adverse effects still popped up: dizziness, dry mouth, fatigue, and insomnia. Because of these concerns, the FDA gave flibanserin a pretty negative review the first time around, unanimously rejecting the drug. The committee did, however, encourage researchers to keep going.

But Boehringer dropped the drug in 2010, admitting that fixing it would be too complex and time-consuming for them. Still, the company added in a statement at the time that it "remained convinced" that flibanserin could one day be a go-to drug for pre-menopausal women. Sprout soon took up the challenge, and has since made FDA approval of flibanserin its mission. It doesn't make for a bad tagline, either — the all-women pharmaceutical company states on its website that it's "led by a woman dedicated to this first for women."

Who Wants To Even The Score

Since picking up the torch for female sexual dysfunction, Sprout has raised its feminist profile through Even the Score, a lobbyist campaign the company co-founded in 2014. The group is already backed by a number of women's rights and health nonprofits, including Change for Health and Gender Equity and the National Organization for Women. Even the Score has also garnered support from high-profile women, such as U.S. Reps. Jackie Speier (D-CA) and Lois Frankel (D-NY). Together, these groups and political leaders have created a new feminist health movement, advocating for gender equality in the treatment of sexual dysfunction.

With their help, Even the Score has been ridiculously successful over the last year. The campaign found its stride not long after the FDA rejected flibanserin for the second time in October 2013. In the months following, as the struggle to bring female Viagra hit its lowest point, the campaign kicked into high gear, its various members spending much of 2014 lobbying the FDA for another shot. And they got it, though not without some rough patches.

In 2014, Sprout filed an appeal with the FDA, claiming that the agency "erred in its assessment of the benefit-risk profile of flibanserin." The company was ultimately denied the appeal, and returned to the lab to conduct additional studies. Earlier in 2015, Sprout was finally able to resubmit a drug application for approval.

In March 2015, Speier, Frankel, and nine other congresspersons sent a letter to FDA Commissioner Margaret Hamburg, applauding the agency for deciding to reconsider flibanserin. "We firmly believe that equitable access to health care should be a fundamental right, regardless of whether you are a man or a woman," read the letter. "But when it comes to sexual health — and, in particular, sexual dysfunction — that is not the case."

The letter continued:

In the past year, the call for gender equity in the approval of treatments for sexual dysfunction has grown louder, with some of the nation’s most prestigious women’s health and other research groups voicing serious concerns about this disparity. We understand many of these organizations have met with Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research, and we hope you take their concerns seriously.

But it appears that not every Even the Score member advocates for flibanserin — at least, not exactly. While NOW President Terry O'Neill has been vocal about finding a treatment option for female Viagra, she told the FDA in a letter late last year that her organization was not specifically endorsing flibanserin:

While we are not necessarily endorsing the product under pending application or any other medical treatment for sexual dysfunction, we believe that a thorough review and re-consideration is due. Certainly, the fact that numerous treatments have been approved by the Food and Drug Administration and made available for men, while none for women have been approved for women should raise questions. We hope that no criticism suggesting a double-standard being applied arises.

What The Critics Are Claiming

The buzz around flibanserin is immense and confusing, particularly for the reason highlighted in O'Neill's letter. Are women's health nonprofits and politicians supporting flibanserin specifically, or are they inevitably boosting a drug simply by advocating for more research into women's sexual health? As Even the Score has pointed out, there is certainly a problem when women's sexual health gets pushed to the wayside. But the dissenting medical researchers say that flibanserin, in its current form, may not be the answer.

As Even the Score gained momentum over the last year, so has the New View Campaign and Georgetown University's PharmedOut — two groups of medical doctors and researchers which remain highly skeptical of flibanserin. Following the recent FDA committee vote, the groups launched a sweeping letter-writing campaign, urging the FDA to reconsider its recommendation of flibanserin and not bow to political or public pressure.

The New View Campaign sees the push for flibanserin as a promotional campaign by Even the Score, one that has gained momentum because of the increasing awareness of gender inequality in drug research. While the group acknowledges this inequality, it has its doubts about flibanserin. Dr. Leonore Tiefer, of NYU School of Medicine and The New View Campaign, said in a letter to the FDA in July that the agency was setting a "dangerous precedent" by folding to what she considers "unethical tactics."

Meanwhile, PharmedOut sent a letter signed by more than 200 medical researchers, doctors, scientists, and sexologists to the FDA in July, stating that women deserve a safer HSDD treatment option. "Flibanserin is minimally effective," the letter claimed. "There is no identifiable population for whom benefits outweigh harms." PharmedOut also highlighted a number of alleged health concerns about the drug, including the possibility of "serious" cardiovascular risks, like low blood pressure and hypotensive episodes. The mixture of flibanserin and alcohol is also a major issue for these doctors, as well as possible impairment while driving.

"Flibanserin is a long-term treatment," the PharmedOut letter states. "Alcohol use is common — especially in conjunction with planned sexual encounters — and the expectation that those who enjoy alcohol will forswear its use forever is unreasonable."

After the drug was approved, Dr. Adriane Fugh-Berman of PharmedOut and Georgetown University Medical Center told Bustle, "It's unfortunate that the FDA has decided to approve a drug with such limited benefits and potentially serious known risks, and that will definitely be used off-label. It's a bad sign for the future of drug regulation."

Sprout Pharmaceuticals counters the groups' claims. A representative told Bustle in an email that a 2014 trial of more than 8,500 women found flibanserin's effects to be safe and minimal:

Two additional Phase I drug interaction studies and a Phase I driving simulator study were conducted in 2014 at the request of the FDA. The drug interaction study further explored how [flibanserin] is metabolized in the liver and found that less common metabolic pathways (CYP 2C9, CYP 2C19) did not play a significant role in [flibanserin] metabolism. The driving study demonstrated that women treated with [flibanserin] at bedtime had no next-day impairment of driving ability.

While Sprout admits that the drug caused some side effects during the trials, including dizziness and dry mouth, the company said in a recent statement that hypotension was rarely seen when flibanserin was taken properly — at night, and without alcohol. Sprout added to Bustle that FDA approval was a "significant step in validating the science and data for the treatment of HSDD, and recognizing the experiences of the women with this condition."

Still, there may be some health warnings to heed. The FDA's flibanserin-prescribing guideline for doctors comes with some serious disclaimers: "Before prescribing, assess the likelihood of the patient abstaining from alcohol, taking into account the patient’s current and past drinking behavior, and other pertinent social and medical history."

The guidelines also warn doctors about adverse risks when flibanserin is combined with oral contraception. The drug should remain off-limits to women with preexisting conditions that cause hypotension, women who have liver impairment, and women who are postmenopausal.

Is This About More Than "Evening The Score?"

PharmedOut and The New View Campaign were not the only medical groups opposing Even the Score. The National Women's Health Network claimed in a recent letter to the FDA that, "The problem with flibanserin is not gender bias at the FDA but the drug itself."

The network, composed of medical nonprofits and researchers, questioned Even the Score's intentions, claiming the group has been manipulating facts as a way to manufacture public outrage. For example, Even the Score says that there are 26 different treatment options of male sexual dysfunction, but the National Women's Health Network claims that's a misleading figure:

[Even the Score] counts each brand name drug and its identical generic counterparts or different formulations as unique treatment options, which artificially inflates the number of drugs available for men ... Nevertheless, the inflammatory claim of gender bias produced press and political attention.

Even the Score sometimes seems vague about their agenda. It is currently leading a letter-writing campaign to Congress this summer, urging political leaders to shine a spotlight on female sexual dysfunction. However, the letter never mentions flibanserin by name. Following Tuesday's FDA approval, the group posted a cheeky video thanking the FDA — not for approving flibanserin, but for taking the "first step toward sexual health equity." The video again touts the disputed 26-drugs-for-men figure.

What Happens Now?

It's important to note that the FDA doesn't take these allegations of gender bias lightly, and the political pressure behind flibanserin seemed to rustle more than a few lab coats. In the briefing report prior to June's committee meeting, the FDA dismissed some of these calls of gender inequity as "inaccurate" and "misleading."

"The FDA rejects claims of gender bias," the agency said in its report. "The FDA’s regulatory decision for each product is based on an assessment of whether the benefits outweigh the risks, and does not take gender into consideration."

Still, the FDA appears to have cut through all that backlash and politics. Flibanserin, which will be sold under the name Addyi, will be available via prescription by Oct. 17. "We applaud the FDA for putting the patient voice at the center of the conversation and for focusing on scientific evidence," Sprout CEO Whitehead said Tuesday in a statement.

But medical researchers like Dr. Tiefer of The New View Campaign remain unconvinced. She told Bustle in an email this week that Addyi's approval will damage the "integrity of the FDA." Dr. Tiefer and The New View Campaign joined the National Women's Health Network statement, which chided the FDA for setting a precedent "that a clever public relations campaign can sway the FDA’s evidence-based, decision-making process."

At this time, the first form of female Viagra will only be administered through a specially-designed risk evaluation and mitigation strategy (REMS). This means that only certified doctors and pharmacies will be allowed to prescribe and administer the drug. So you should put away any hopes of flibanserin becoming near-ubiquitous, kick starting a 21st-century sexual revolution, and rivaling the sweeping legacy of the birth control pill.

The little pink pill is finally here, but it may not be the feminist game-changer we were expecting.