Flibanserin is being touted as a drug designed to boost the low sexual desire of otherwise healthy women. Here's how it works and why it's really not like Viagra at all. (The Washington Post)

This post has been updated.

The Food and Drug Administration approved the world's first drug designed to boost a woman's sexual desire. The path for flibanserin, made by Sprout Pharmaceuticals, has been a rocky one, in part because the science of desire is little understood, and in part because there is disagreement on what constitutes "normal" sexual desire. Once a host of other common factors for flagging desire are ruled out - medical conditions, sex-hormone depletion, relationship troubles, some antidepressants, cultural or religious messages, poor body image - questions remain.

[FDA approves controversial ‘female Viagra’ drug]

Is it mismatched libido with a partner with a higher sex drive, as some contend? Is monogamy just boring? Or is it biology? And the biggest question: how will the ability to pop a pill change the nature of sex, relationships and intimacy?

Here is a chronology of medical and pharmaceutical efforts to deal with the issue:

1952: Frigidity and Impotence are listed as sexual disorders in the first Diagnostic and Statistical Manual of Mental Disorders.

1953: FDA approves Delatestryl, an injectable testosterone replacement therapy for men. Since then, more than two dozen other testosterone replacement treatments for men -- injectables, pills and gels, have received FDA approval. (Years later, the FDA warns that aging should not be the only reason for testosterone replacement therapy, because of a heightened risk of cardiovascular events. By 2012, prescriptions for testosterone have soared to half a billion; an editorial in the Journal of the American Geriatrics Society earlier this year blames direct-to-consumer advertising for the surge.)

Alfred Kinsey publishes “Sexual Behavior in the Human Female” based on interviews with nearly 6,000 young, white females. Though he doesn’t focus on sexual desire, he writes that females have sex about twice a week until the age of 50, and then an average of once a week. In his study, 69 percent of females reported erotic fantasies about males.

1964: Reid-Provident Laboratories, later acquired by Solvay Pharmaceuticals, puts Estratest, an estrogen/testosterone product for menopausal women with hot flashes and low desire, on the market. It never receives FDA approval. (A federal judge in 2010 approves a $16.5 million class action settlement against the company for falsely marketing the drug as FDA approved.)

1966: William Masters and Virginia Johnson publish the groundbreaking “Human Sexual Response,” based on direct observations of 382 women and 312 men. They write for the first time that women, unlike men, are capable of multiple orgasms, and that the physiology of clitoral and vaginal orgasms is identical. (Sigmund Freud claimed clitoral orgasms were “immature and inferior.”)

They also describe, for the first time, the sexual-response cycle: Excitement or Arousal. Plateau. Orgasm. Resolution. Like Kinsey, they don’t focus on sexual desire. The study is criticized for using “sexual extroverts” that make it non-representative.

1974: Helen Singer Kaplan, a sex therapist and founder of the first clinic for sexual disorders at a medical school, introduces the idea that desire is what sparks the human sexual-response cycle: Desire. Arousal. Orgasm. She maintains desire disorders are the most difficult to treat because they’re associated with psychological difficulties.

1980: The diagnosis of Inhibited Sexual Desire, of ISD, is added for the first time to the DSM III. ISD is later renamed Hypoactive Sexual Desire Disorder, HSDD in the DSM IV. HSDD is defined as the “persistently or recurrently deficient (or absent) sexual fantasies and desire for sexual activity” that results in marked distress or interpersonal difficulty.

1991: Pfizer chemists in the United Kingdom experiment with a new blood pressure medication. The drug doesn’t work on hypertension, but it does result in “marked” erections. Viagra is born.

1994: The Massachusetts Male Aging Study reports that 52 percent of men are affected by erectile dysfunction, which increases with age. At age 40, 40 percent of men are affected. At age 70, nearly 70 percent are. The prevalence of total ED increases from 5 to 15 percent as men age from 40 to 70.

The FDA approves Premarin, an estrogen cream produced by Pfizer, to treat vaginal atrophy and dryness in post-menopausal women, which can cause pain during sexual intercourse, dyspareunia, and lower desire. The FDA approves similar treatments, Novo Nordisk's Vagifem in 1999, Shionogi Inc.'s Osphena in 2013.

March 1998: FDA approves Viagra for erectile dysfunction in men.

1999: The Journal of the American Medical Association publishes a study that finds 43 percent of American women suffer from sexual dysfunction, compared to 31 percent of men. Some researchers immediately challenge the conclusion.

A group of doctors, nurse practitioners, sex therapists, scientists and academics gather to form what will become the International Society for the Study of Women’s Sexual Health, ISSWSH, with ties to the pharmaceutical industry, to foster the scientific study of female sexual function and dysfunction.

2000: Leonore Tiefer, a sex therapist and researcher, organizes the New View Campaign maintaining that sex is complicated, there’s a whole range of “normal,” and that female sexual dysfunction is a construction of the pharmaceutical industry. The group begins advocating against the “medicalization of sex.”

The FDA issues draft guidelines for research protocols for drug development for Female Sexual Dysfunction. The guidelines have never been formalized.

FDA approves the EROS clitoral therapy device, a vacuum pump that creates suction around the clitoral region to increase blood flow and aid in sexual arousal. Available by prescription only, the device cost about $359.

FDA approves testosterone gels for men, AndroGel and Testim.

2001: Rosemary Basson offers a different view of female sexual desire, that arises after arousal, not before, and proposes a new model of human sexual response for women, suggesting that it's driven by a desire to enhance intimacy: Neutrality. Sexual stimulus. Arousal. Desire. Emotional and physical satisfaction. Emotional intimacy.

2004: Pfizer pulls the plug on studies of Viagra to treat women's low sexual desire, after eight years of work and tests with 3,000 women. The drug enhances blood flow to the genitals for both men and women. But while genital arousal typically leads to desire for men, Pfizer found that wasn’t the case for women. “There’s a disconnect in many women between genital changes and mental changes,” Mitra Boolel, leader of Pfizer’s sex research team, told The New York Times. Pfizer says they’ll shift research focus to women’s brains.

Procter & Gamble files a new drug application for a testosterone patch called Intrinsa, to treat Hypoactive Sexual Desire Disorder in women who had gone through surgical menopause after having their ovaries removed. Though the FDA and an advisory committee agree the patch was effective, they worry that the risk of breast cancer and coronary disease outweighs the benefits and ask for further safety studies. P & G withdraws the application.

2005: Journalist Ray Moynihan publishes an article in the British Medical Journal: “The marketing of a disease: female sexual dysfunction,” arguing that the pharmaceutical industry is turning normal variation in sexual desire into a disease in order to create a new, profitable market.

2006: The European Medicines Agency approves Intrinsa for women with surgically induced HSDD. In 2012, the European drug marketer withdraws the drug “for commercial reasons.”

Alista, another testosterone treatment for women with low desire being developed by Virus Inc, fails in a mid-stage clinical trial.

Boehringer Ingelheim seeks to create a quick-acting antidepressant, flibanserin, and finds that, instead of dampening libido, as most antidepressants do, the drug boosts it for women, but not men.

2008: A study of 31,000 women in The Prevalence of Female Sexual Problems Associated with Distress and Determinants of Treatment Seeking (PRESIDE) study, published in Obstetrics & Gynecology, finds that one in 10 women may receive a diagnosis of HSDD. Another study of 3,500 women finds that HSDD ranges from 6 to 13 percent in Europe and 12 to 19 percent in the U.S.

2009: Boehringer Ingelheim files a new drug application with the FDA for flibanserin, (proposed trade name Girosa) to boost sexual desire in pre-menopausal women. Originally developed as an antidepressant, flibanserin was found to boost desire by working on reward and inhibitory neurotransmitters in the brain. Unlike Viagra, which is taken on an as-needed basis, flibanserin is to be taken every evening.

A survey of physicians finds that between 2006 and 2007, two million testosterone prescriptions were written off-label for women with HSDD, although there’s no consensus on appropriate testosterone therapy levels for women.

June 2010: An FDA advisory panel unanimously recommends that the FDA reject flibanserin, saying that daily diaries of desire showed the drug worked no better than placebo. B & I argues that using a different measure, the Female Sexual Function Index - Desire, the drug’s efficacy is statistically significant over placebo. The FDA panel contends the company can't change the rules to suit the outcome.

October 2010: B & I announces it is discontinuing the development of flibanserin.

2011: Sprout Pharmaceuticals acquires flibanserin. It says the drug may be used to treat up to 16 million women.

The FDA states that Female Sexual Dysfunction, which includes HSDD, is one of 20 key “unmet medical needs” with no FDA-sanctioned safe and effective treatments available.


A tablet of flibanserin. (AP/Allen G. Breed)

December 2011: BioSante Pharmeceuticals announces the failure of phase three clinical trials of Libigel, a testosterone gel designed for surgically menopausal women with HSDD. The gel failed to work better than placebo in boosting desire. The news wipes out more than three-quarters of the company’s value in trading the following day.

2012: The global erectile dysfunction market reaches $4.3 billion for Viagra, Cialis, Stendra/Spedra, Levitra, Staxyn, MUSE, Zydena, Mvix and Helleva, according to a report by Transparency Market Research.

2013: The definition of HSDD is revised again and included as part of Female Sexual Interest/Arousal Disorder in the DSM V. For a diagnosis of FSIAD, the absence of desire or arousal must be present for at least six months, cause “significant distress,” and not be related to partners, relationship, medical, cultural or religious factors, body image, depression or other stressors.

June 2013: Sprout resubmits an FDA new drug application for flibanserin, which is to be marketed as Addyi, with additional data. FDA rejects the submission, saying that the risks of taking the drug – sleepiness, dizziness, fainting, fatigue and nausea - outweigh the modest benefit, and over concerns about unknown long-term effects. They request additional studies for drug-drug interactions and a driving study to test the effects of sleepiness.

December 2013: Sprout appeals, and files a request for a Formal Dispute Resolution with John Jenkins, director of the FDA’s Office of New Drugs. ISSWSH sends a petition with 4,000 signatures urging the FDA to approve flibanserin. FDA asks Sprout to complete the additional studies.

April 2014: A group of women’s health organizations, including the New View Campaign, Our Bodies Ourselves, the National Women’s Health Network and the American Medical Women’s Association, write a letter to FDA Director Janet Woodcock, urging the FDA to reject flibanserin, because the “minimal benefit does not outweigh the risks.”

June 2014: A coalition of 24 progressive, health and women’s organizations, backed by Sprout Pharmaceuticals, launch an Even the Score campaign, charging the FDA with “persistent gender inequality” when it comes to sexual dysfunction. The groups say the FDA has approved 26 drugs to treat sexual dysfunction for men (41 counting generics) and none for women. Critics point out many of the drugs are different formulations of the same treatment, testosterone.

October 2014: FDA holds a two-day hearing on female sexual dysfunction and the “unmet medical need” for treatment. Sprout Pharmaceuticals pays for several women diagnosed with HSDD to travel to the hearing.

February 2015: Sprout resubmits flibanserin, including the additional safety studies requested. They cite three trials that show that between 46 and 60 percent of the women involved responded to the drug, and that levels of desire and the number of satisfying sexual events increased, and distress levels decreased, at rates modestly higher than placebo.

March: Even the Score announces 11 members of Congress have written FDA Commissioner Margaret Hamburg to urge the approval of flibanserin, in addition to earlier pleas from five other lawmakers. All are Democrats.

June 1: An Even the Score online petition drive on change.org to change "#HERstory," urging the FDA approve flibanserin, garners more than 60,000 signatures. A New View online petition on change.org urging the FDA to reject flibanserin garners 652 supporters.

June 4: An FDA advisory committee votes 18-6 to recommend the FDA approve flibanserin for premenopausal women with conditions – a risk evaluation and mitigation strategy, including warnings not to take the drug with anti-fungal medications or alcohol. 

June 5: The stock price of Palatin Technologies, manufacturers of another female desire medication seeking FDA approval, soars 46 percent, Business Insider reports.

August 18: FDA approves flibanserin.

October 17: Sprout Pharmaceuticals intends to make the drug available.

An earlier version misidentified the manufacturer of Premarin. This version has been corrected.

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