Osphena, as the recently FDA-approved drug is called, is the newest answer for painful sex. The drug's creator, pharmaceutical company Shionogi, Inc., is particularly interested in the more than 64 million U.S. women who have hit menopause, half of whom, it claims, could use the drug. In theory, that's a lot of women who could be having a lot better sex, and soon.
If even a fraction of those women are interested, the drug's approval could be the start of a long-awaited dream for the pharmaceutical industry, which has labored for decades to define a catchall disorder of women's sexuality and then develop a series of drugs to help. It's been a fraught process, in which pharma has been accused of inflating numbers and has failed time and again to satisfy drug safety regulators at the FDA.
So it's no wonder that some connected to the industry are crowing. Osphena “is a milestone in women's menopause therapies,” says Margery Gass, a practicing gynecologist in Cleveland and executive director of the North American Menopause Society, which lists the drug's manufacturer among its corporate liaison council. “It's really good to have ... options for women at this point in life.”
But as the FDA allows Osphena (ospemifene) to head to market in June and Shionogi launches its “public education” campaign, starting with physicians, questions abound. First about whether this is a real disorder affecting a large percentage of American women. Second about how Osphena was approved. And third about whether Osphena, which mimics estrogen and has similar known downsides, may also be a back-door, off-label replacement for “hormone replacement therapy,” which was discredited a decade ago.
Menopause is as much a “disease” as adolescence, and it wasn't considered a problem until the 1960s, when drugmakers like Wyeth-Ayerst, Upjohn, and Searle effectively rebranded it a disorder of “estrogen deficiency”0 — and that was the term they used when they were being polite. The 1966 industry-funded book Feminine Forever declared menopause “a tragedy,” a “living decay,” and asserted that in the absence of estrogen a woman would “be condemned to witness the death of her own womanhood.” A 1977 ad for Premarin, an estrogen derived from pregnant horses' urine, shows a family cowering from their crazed matriarch: “Almost any tranquilizer might calm her down,” reads the copy, “but at her age estrogen might be what she really needs.”
Sales of estrogen dipped in the late 1970s, when the hormone was linked to an eightfold increase in endometrial cancer, then picked back up in the 1980s in combination with progestin to counter the endometrial effects, at which point it became “hormone replacement therapy.” Wyeth responded by creating the two-drug pill Prempro, which was approved in 1995, and by reportedly ghostwriting medical articles that downplayed risks and implied unproven benefits, like protection from dementia and even enhanced eyesight, better skin, and self-esteem. At its height in 2001, menopausal hormones comprised a $2 billion industry.
At around the same time that the menopause market was peaking, a new drug in the area of male aging was setting records: Viagra. Eager to replicate the little blue pill's success, the definition of “female sexual dysfunction” was hammered out at meetings reportedly funded by pharmaceuticals and introduced into the lexicon by pharma-sponsored opinion makers like Laura and Jennifer Berman. On morning talk shows and in reported articles, they and other experts contended that nearly half of all women were dysfunctional: 43 percent, a number that became gospel among both medical and lay audiences.
Medical journalist Ray Moynihan dissected the term and the number in a 2003British Medical Journal article, reporting that it was derived from a survey of just 1,500 women. If a respondent answered “yes” about having experienced any one of seven problems for two months or more during the previous year — for example, lack of desire, anxiety about performance, or lack of lubrication — then they were considered dysfunctional. The study, though, did not take life context into account: what if a woman had low desire for two months because her father was dying or had lost her job or was taking care of a newborn baby?
Critics call this disease-mongering: drug manufacturers market a disease — the industry term is “condition branding” — priming the widest possible consumer base. In the documentary Orgasm, Inc., which will air on Free Speech TV April 30 and May 1, an executive of the company Vivus, which tried and failed to launch a Viagra-like cream for women, explains, “In order for us to develop drugs, we need to better and more clearly define what the disease is.”
Pharma's success in defining menopause, however, was to suffer a major blow. Even while hormone replacement therapy was on the rise, the National Institutes of Health launched the Women's Health Initiative (WHI) study to examine large-scale prevention efforts to address threats to women's health like heart disease and breast cancer. Part of the study would test whether estrogen protected women from heart disease, as the drug companies had long claimed. Begun in 1997, the study was supposed to last 8.5 years. But by 2002 it was halted: the NIH announced that the treatment led to an increased risk not only for heart attack, but also breast cancer and stroke.
Women and their doctors grew estrogen-wary. Suddenly, a drug that had been recommended to all menopausal women as a preventative was something to use with caution, only in women with unbearable symptoms and for the shortest duration possible. For years, clinicians based their practice on “theories driven by company marketing, and when the Women's Health Initiative results came out, all of that was disrupted, suddenly we had real evidence that much of these claims weren't true,” explained Amy Allina of the National Women's Health Network.
Pharmaceutical companies like Wyeth, maker of Premarin and Prempro, (which has since merged with Pfizer) saw their profits plummet in the years following the NIH report. Wyeth continued waging a public-relations campaign in the pages of medical journals and in the halls of medical conferences, tweaking their message but continuing to promote hormone use. And just last month, the International Menopause Society, which has strong ties to the industry, released a “Global Statement on Menopausal Hormone Therapy,” which recommends that the estrogen-progestin combo is safe and beneficial as long as the women who take it are under the age of 60 and within 10 years of starting menopause.
“Hormone therapy is definitely being reframed,” said Adriane Fugh-Berman, who has written about medical ghostwriting specifically in the menopause market. She coauthored a 2011 study that analyzed some 50 opinion articles following the Women's Health Initiative and found that more than half were “promotional in tone,” either attacking the WHI, downplaying the risks of estrogen, exaggerating its benefits, or implying new ones. It also found that 8 out of 10 authors studied had declared payment from menopausal hormone manufacturers.
These efforts appear to have had the intended effect. Surveys of ob-gyns in the years since the WHI have consistently found that about half don't believe the results of the government study, which included more than 16,000 women. “The industry creates an atmosphere. If you get to enough key opinion leaders, then marketing messages become conventional wisdom. People who don't have conflicts of interest begin repeating them as well,” Fugh-Berman said. “I've been yelled at by entire rooms of doctors, I've been told that denying women hormones was genocide.”
Fugh-Berman, who directs the PharmedOut project at Georgetown University, which aims to expose industry influence in medicine, sees this as part of estrogen's long history. “First it was sold to keep you 'feminine forever,' then it was sold as disease prevention, now it's being recast as safe in the low-dose formulation.” (Following the WHI, Wyeth subpoenaed the NIH for the study's raw data.)
That message and promotional tone can be found in the 2011 documentary Hot Flash Havoc, a film that has no overt industry funding but reflects its views. The film, which screened in theaters and libraries around the country and which the Los Angeles Times called “vital and enlightening,” argues that the government “misrepresented” the WHI, which resulted in women flushing their pills en masse and needlessly suffering, shriveling into sexless raisins. The film purports that 70 percent of menopausal women have sexual problems. “We have every major menopause expert in the country interviewed in the film and they all say the same basic thing,” Alan Altman, the film's medical consultant, said somewhat hyperbolically. Their message, he said, is that the Women's Health Initiative study got it wrong by giving estrogen to women who were too old to benefit from it. “Estrogen is a preserver of good function. It doesn't repair bad function 20 years down the road,” he told me. “You should be angry as a woman.”
Garnet Anderson, principal investigator of the WHI clinical coordinating center, called this “wishful thinking. There are no data to support that estrogen plus progestin is safe in younger women.” “Part of the problem with the film is that it promotes some of the old ways of thinking about menopause,” said Allina of the National Women's Health Network, which was asked for an endorsement and declined. The North American Menopause Society was also asked and declined — “we felt that it wasn't balanced enough,” said Gass. Judy Norsigian, coauthor of the classic handbook Our Bodies, Ourselves, told me: “I don't like this film and I'm sorry I'm in it.”
None of this is to say that no women benefit from hormones — in fact, the WHI found that women who'd had hysterectomies absolutely do — nor is it to say that women's sexual dysfunction doesn't exist or that it's not recognized by mainstream medicine. Several disorders appear in the Diagnostic and Statistical Manual in the categories of desire, arousal, orgasm, and pain, and clinicians are now instructed to make a diagnosis only when the symptoms result in “personal distress.” Drug manufacturers must get approval to treat a DSM-recognized disorder, such as Osphena's target, dyspareunia.
“There are women who have dyspareunia, I'm not denying that at all,” said Loren Wissner Greene, an ob-gyn and bioethicist at New York University. Women's circulating estrogen decreases in menopause (though the ovaries don't shut down altogether, as is often reported), and like the rest of our skin and muscle, the vulva and vagina experience some thinning and drying. This has a medical term, which Shionogi uses in its promotional web site VVAvoices.com: vulvo-vaginal atrophy. That dire-sounding description is itself questionable, since all women will experience it to a degree, the same way we get wrinkles and gray hair.
Greene is skeptical about both Osphena and what she calls the “propagandizing” of female sexual dysfunction. “To me, FSD is women feeling that they're inadequate,” she said, which she believes leads them to do risky things like take drugs they don't need and get labial-reduction surgery. The conservative estimate echoed by Greene and Gass is that just 10 percent of menopausal women need medical attention, far less than the 70 percent indicated by Hot Flash Havoc or the 60 percent cited by Osphena's own drug application. They also suggest that there are safer ways for many women to sidestep these problems. Just like the recommendation to keep exercising as we age, Greene and other physicians point out that women who stay sexually active throughout menopause tend to do better than women who don't. “Use it or lose it,” they say. Sex, it turns out, is a preserver of good function. Greene also recommends lubricants, physical therapy, and topical estrogen creams. Even though they contain estrogen, less of the drug is absorbed by the body from a cream than from a pill like Osphena, according to Greene.
For women with persistent problems, the question remains how well Osphena works and whether it is worth the risks. Osphena is a SERM — a selective estrogen-receptor modulator — in the same class as powerful drugs like tamoxifen (used to prevent breast cancer) and Clomid (to stimulate ovulation). On the “black box” warning that will feature prominently on Osphena's label, risks include cancer, blood clots, and stroke. But other bothersome side effects showed up in clinical trials: women taking the drug had twice the rate of urinary tract infections, three times the rate of hot flashes, and 14 times the rate of yeast infections. Also: the package says Osphena shouldn't be mixed with fluconazole, which is often prescribed for stubborn versions of the latter.
Critics also note that the two 12-week trials that satisfied the FDA were funded by the drug's developers, Shionogi, Inc. and QuatRx, a practice that is common but might give the public pause. Two of the lead authors, David J. Portman and James A. Simon, list so many consultancies, speakers' bureau affiliations, and board memberships with pharmaceuticals (including Shionogi and QuatRx) that the disclosures take up half of the study's first published page in Menopause, the journal of the North American Menopause Society. Also, The New York Times reported that Gloria A. Bachmann, another lead author, between 1998 and 2005 signed her name to ghostwritten papers that downplayed the risks of estrogen without disclosing that Wyeth had paid for them.
Alan Cassels, who researches drug policy at the University of Victoria and co-authored the book Selling Sickness with Ray Moynihan, looked over Osphena's application and studies. “I'm amazed it got approved,” he said. While investigators report a statistically significant improvement for women's “most bothersome symptom,” at 12 weeks that difference was less than half a percent between the women taking the drug and those on placebo. “You can make it sound very statistically significant, as they've done,” he said. “But how does that translate into something meaningful for a person's life?” A company spokesman disagree but did not elaborate.
Barbara Mintzes, who studies drug marketing at the University of British Columbia, also gave the FDA application for Osphana a read. She notes that while roughly 14 percent of women (over placebo) had an alleviation of symptoms, a similar percentage of women also experienced an adverse event, like an infection. “This is not a positive ratio of benefit versus harm,” she wrote in a detailed email to Newsweek. Ideally, she says, you'd want to see the benefit outweigh the harm “by a good margin.” “These are very disappointing results — no one wants to take a medicine that is equally likely to make them worse as to make them better.” Shionogi disputes this analysis.
Shionogi, Inc. responded to criticisms by email. “The FDA established that the benefits of treatment with Osphena outweigh the potential risks.” Vulvo-vaginal atrophy “is a real condition,” spokesperson Ginger Constantine wrote, “caused by decreased estrogen levels due to menopause in women.”
If Osphena is just the tip of the pharmaceutical iceberg, women have a lot to look forward to: testosterone gels and nasal sprays, antidepressants rebranded as libido enhancers, maybe even high-tech vibrators that will be covered by medical insurance. But the question still stands: will these treatments bring more pleasure to women or to the pharmaceutical industry?
This article was reported in partnership with The Investigative Fund at The Nation Institute.