Do Women Need Their Own "Viagra"?
On June 5, 2015, U.S. news headlines proclaimed “FDA Panel Endorses Female Viagra.” This was inaccurate, because after two denials, it was only the advisory committee to the Food and Drug Administration (FDA) who voted favorably to recommend that the FDA approve the drug Flibanserin® in August. The FDA wants more information on side effects of the drug, including dizziness, nausea, fatigue, insomnia, and the effects of alcohol. Flibanserin® is touted as a treatment for Hypoactive Sexual Desire Disorder (HSDD) for premenopausal women, which is defined as the persistent lack of sexual fantasies and desire that is distressful to the individual. An estimated 10% of women experience this distress, which is why these headlines caught most people’s attention.
Sildenafil (Viagra®) is a performance-enhancing drug for erectile dysfunction, not a form of testosterone. Penile erection results when nitric oxide produces 3’5’cyclic GMP, causing dilation of the blood vessels of the corpus cavernosum of the penis, resulting in an erection. This process is controlled by the enzyme phosphodiesterase (PDE-5), which can inactivate cGMP to impair vasodilation of the penile blood vessels. Sildenafil blocks PDE-5, thus enhancing the effects of cGMP to sustain the erection.
Testosterone therapy has been used off-label as a treatment for HSDD, despite the fact that many studies show no association between androgen therapy and female sexual function. There is no FDA-approved form of testosterone for women. The FDA has remained concerned regarding major (cardiovascular disease and breast cancer) and minor (acne and hair growth) side effects of this drug.
Flibanserin®, in contrast, interacts directly within the complex network of neural hormones in the central nervous system that influence sexual behavior. Sexual arousal and desire are a product of competing influences between the stimulating effects of dopamine and the inhibitory effects of serotonin. Moreover, estrogen and testosterone stimulate dopamine release to enhance sexual desire, while a complex balancing of various serotonin receptors determines the repressive effect of serotonin. Flibanserin® is a serotonin 1A (5 HT1a) receptor agonist, a serotonin 2A (5HT2a) receptor antagonist, and a dopamine D4 receptor partial agonist, meaning the drug has both stimulating and blocking capabilities depending where in the brain it is functioning.
Results of a number of studies support Flibanserin®’s impact on sexual activity and the neural hormones involved. In rats, increases in norepinephrine (a product of dopamine) and decreases in serotonin were documented in all brain areas associated with sexual behavior. From the FDA Advisory Committee Document (2015) in all three phase 3 human clinical trials of Flibanserin®, women reported improvements in sexuality of 9.4% to 14.6% over placebo-treated women.
Arousal and desire for men and women are as much psychologic as biologic. Basic questions that often dominate any discussion of intimacy in the gynecologist’s office are “Do you like yourself? Do you like your partner? Who does the lack of desire or libido bother, you or your partner? And finally, do you want to improve how you feel about your sexuality?” Armed with these answers, the gynecologist is able to navigate toward a more productive discussion and strategy for care.
There is a great deal of interest on the part of pharmaceutical companies to help women with HSDD for obvious market volume reasons. Since sexual desire dysfunction is multifactorial in women, often involving relationship issues and intimacy as well as possible anxiety and/or depression, it is unlikely that one pill will be a simple solution. Stay tuned for the update in August after the FDA reviews the recommendations.
By James Woods, M.D. and Elizabeth Warner, M.D.
References Available Upon Request
James Woods, M.D. is a practicing gynecologist certified in menopausal medicine and a regular contributor to Rochester Woman Magazine. Elizabeth Warner, M.D., is a retired gynecologist living in Rochester, NY. For questions regarding this menoPAUSE or other menopausal issues you would like to see addressed in future editions, please call him at (585) 271-7800 or email him at james_woods@urmc.rochester.edu.
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James Woods | 8/3/2015
