Ladies out of Luck: FDA Blocks “Female Viagra”

Guys who need it have Viagra; Ladies with the similar needs have nothing now that the FDA has denied approval of a new drug, flibanserin, which would treat sexual dysfunction in women. What’s interesting from a neuroscience perspective is how the drug works.  What’s interesting from a social perspective is how difficult it is to address this medical concern in women pharmacologically.

            The FDA denied the new drug application by Sprout Pharmaceuticals in October, 2013 asking for more proof that flibanserin treatment works.   The company just announced that it will appeal.   It’s pretty simple to prove that Viagra works.  That drug acts on the vascular system to boost vapid hydraulics in the penis.  But it is not so simple to prove a libido lifting drug works for females.  Human sexuality is difficult to model in animal experiments.  Even in clinical studies it can be difficult to design human experiments that lead to clear conclusions because human sexual behavior is complex, especially so in woman most would agree.  In contrast to Viagra, what exactly would a drug target in women whose biological sexual response is a bit more complicated than boosting blood flow?  Flibanserin is not a hormone.  It does not target the body at all.  It targets the brain.

Women with hypoactive sexual desire disorder (HSDD) simply experience no desire for sexual activity, which can undermine wellbeing and interpersonal relationships just as impotence does for men.  Flibanserin acts on neurotransmitters that are involved in sexual desire and pleasure, stimulating actions of the neurotransmitters dopamine and norepinephrine and reducing serotonin activity.  If you follow the logic behind this pharmaceutical, it is suddenly quite obvious that a person with deficiencies in these neurotransmitter systems could have problems with sexual function.  Indeed, sexual desire in people is complex and it can be quite fragile to stresses of many types.  Sexual dysfunction is also associated with many mental illnesses and mood disorders.  Moods are, after all, the product of specific neurotransmitters acting on circuits in the brain that control emotion.  So what’s the recent published experimental evidence say about flibanserin in promoting increased libido in females?

Simon et al, at George Washington University School of Medicine, reported in November, 2013 in the journal Menopause, on flibanserin acting as a serotonin receptor 2A antagonist and serotonin 1A agonist to treat HSDD.  The study included 468 premenopausal women receiving the drug and an equal number receiving a placebo for 24 weeks.  The results show a statistically significant improvement in number of satisfying sexual events in women treated with the drug; the size of the effect, however, was quite small.  There were also adverse side effects reported, including dizziness, sleepiness, nausea, and headache.

A study published this month in the journal Psychopharmacology by Galez et al, from the University of Versailles Saint-Quentin-e Yvelines, France, tracked the action of the drug in the brains of female rats.  A gene called c-fos is a well-known marker of neural activity.  Simply staining brain tissue in the appropriate way to see if c-fos is turned on in cells allows researchers to determine if a particular neuron is firing actively.  The study shows that the drug increased activity in several brain regions, including the nucleus accumbens, arcuate hypothalamic nucleus, locus coeruleus, and other areas known to be active in females during sexual arousal.  These brain regions belong to the mesolimbic dopaminergic pathway and hypothalamic structures that integrate sexual cues and influence sexual motivation.  The problem is that this result simply shows that the drug acts on the neurotransmitter receptors that it is known to interact with chemically.  The behavioral consequences were not studied.

In a review article published in 2012, Fooladi and Davis, at the Monash University, Melbourne, Australia, examined the literature on a wide range of potential drug treatments for female sexual dysfunction, including data on flibanserin available at the time.  They found no non-hormonal drugs, including flibanserin, that are clearly beneficial.

They did conclude that systemic testosterone, however “has been demonstrated to be effective for the treatment of HSDD and have a good safety profile.”  This is encouraging because there are already testosterone pharmaceuticals approved for treating males.  In fact, two million prescriptions for testosterone treatment have been written for women in 2006 and 2007, according to the article, representing approximately 21% of all testosterone prescriptions (that are intended for males).  The FDA has not approved testosterone use in women for treating HSSD.  “This provokes the question as to who the regulators are most concerned about protecting?” the authors ask.  The experts see a contradiction when the compound is approved for men but it raises serious safety issues when used for women, even though women represent 21% of the people who are taking the drug today without adverse health issues.  (Testosterone is a naturally occurring hormone in females too.)

According to the CBS news article by Castillo, two large studies failed to show a benefit of testosterone patch or gels for women and the European Medicines Agency withdrew marketing authorization for it in 2012, leaving women with no approved medication that is effective in treating this medical condition.

References

Castillo, M.  CBS News December 11, 2013, 2:06 PM http://www.cbsnews.com/news/manufacturers-of-female-viagra-flibanserin-appeal-fda-denial/

Fooladi, E., and Davis, S.R. (2012)  An update on the pharmacological management of female sexual dysfunction.  Expert Opin Pharmacother. 13:2131-42.

Gelez, H., (2013)  Brain neuronal activation induced by filbanserin treatment in female rates.  Psychopharmacology, 230:639-52.

Simon, J.A., et al., Efficacy and safety of flibanserin in postmenopausal women with hypoactive sexual desire disorder:  results of the SNOWDROP trial.  Menopause, Nov 25 e-pub ahead of print.

See also: Sprout Pharmaceuticals Appeals FDA Decision On New Drug Application For Flibanserin To Treat Hypoactive Sexual Desire Disorder In Premenopausal Women
http://www.prnewswire.com/news-releases/sprout-pharmaceuticals-appeals-fda-decision-on-new-drug-application-for-flibanserin-to-treat-hypoactive-sexual-desire-disorder-in-premenopausal-women-235380991.html

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Douglas Fields

About Douglas Fields

R. Douglas Fields is Chief of the Nervous System Development and Plasticity Section at the National Institutes of Health, NICHD, in Bethesda, Maryland, and author of the new book about sudden anger and aggression “Why We Snap,” published by Dutton, and a popular book about glia “The Other Brain” published by Simon and Schuster. Dr. Fields is a developmental neurobiologist with a long-standing interest in brain development and plasticity, neuron-glia interactions, and the cellular mechanism of memory. He received degrees from UC Berkeley, San Jose State University, and UC San Diego. After postdoctoral fellowships at Stanford and Yale Universities he joined the NIH in 1987. Dr. Fields also enjoys writing about neuroscience for the general public. In addition to serving on editorial boards of several neuroscience journals, he serves as scientific advisor for Odyssey and Scientific American Mind magazines. He has written for Outside Magazine, The Washington Post Magazine, Scientific American and Scientific American Mind, and he publishes regularly for The Huffington Post, Psychology Today, and Scientific American on-line. Outside the lab he enjoys building guitars and rock climbing.

The opinions stated in the blog are the personal opinion of the author and not those of the federal government.

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