Female Viagra.”Hypoactive sexual desire disorder” to which the indication for the new drug refers, is very controversial”.

On 4th June this year, a United States Food and Drug Administration (FDA) advisory committee, responsible for the regulation and authorisation of drugs, recommended the approval of flibanserin as a novel medication for the treatment of pre-menopausal women with “hypoactive sexual desire disorder”. The FDA awarded it marketing approval on 19th August.

Its indication suggests — although it is not the same substance — that it is equivalent to the female version of the male “Viagra”, with subtle differences. Unlike Viagra, which is only taken before sex in the case of erectile dysfunction, the new drug should be taken regularly on a daily basis at bedtime in order to minimise the side effects, regardless of whether or not the person intends having sex. This presents a new scenario, given the continuity of treatment and the likely side effects that could appear with time.
This recommendation has not been free of controversy. The FDA had refused to approve the medication with the designated indication on three previous occasions, as it considered that the risk/benefit balance did not justify its authorisation.

A new drug?

Flibanserin is not new. It is actually a molecule that was initially promoted as an antidepressant, but clinical trials were unsuccessful. At the beginning of this century, the pharmaceutical company responsible for this substance was Boehringer Ingelheim. After its failure, it was decided to test its efficacy as a treatment for the disorder known as “hypoactive sexual desire disorder”, which was said to affect 10% of women. The current proprietor is Sprout Pharmaceuticals, which defines itself as a promoter of women’s sexual health.1

The problem of “hypoactive sexual desire disorder”

Although the problems associated with lack of sexual desire are real and not uncommon, the name “hypoactive sexual desire disorder” to which the indication for the new drug refers, is very controversial.
The name has been removed from the latest edition of the “Diagnostic and Statistical Manual of Mental Disorders”, DSM-5,2 which includes a new name: sexual interest/arousal disorder. This has much stricter diagnostic criteria that better captures the complexity of the female sexual experience, and significantly reduces the prevalence of the disorder to only a fraction of the 10% previously estimated. The reason for this amendment is none other than to reduce the “overdiagnosis” that was occurring with the previous name and evaluation of the disorder. This means that the number of women who are candidates for treatment with the new drug has been significantly reduced.
According to a recent study,3 a member of the committee involved in this amendment, psychologist Lori Brotto, concluded that a lack of spontaneous sexual desire, could, in fact, be normal for most women, many of whom enjoy their sex life, and that this should not be pathologized. Another member of the working group, Cynthia Graham, went even further, stating that “there is no disorder of [sexual] desire”.

Flibanserin, a controversial approval

In 2010, an FDA advisory committee voted unanimously against its authorisation, in view of the absence of evidence of a clear benefit in its use, compared to serious safety issues. Most members of the committee were women. Shortly afterwards, following the committee’s recommendations, the FDA rejected authorisation for its use.
In 2013, it again ruled against its marketing, for similar reasons. The FDA did not find any evidence to support the efficacy of flibanserin in either of the two studies conducted in 2010, both funded and presented by the company. In contrast, they did find numerous side effects associated with the treatment, such as nausea, dizziness, fatigue, drowsiness and sedation, which resulted in almost 15% of the women included in the clinical trial having to abandon the study prematurely. Other more severe effects, such as depression and fainting, also occurred to a greater extent among the women who participated in the study and took flibanserin, compared to those who were given placebo.4 Furthermore, one third suffered respiratory tract infections, while one in 25 suffered adverse effects described as severe.
More recently, in 2013, a new trial sponsored by the same company (Sprout), found poor efficacy in the use of the drug, reporting that pre-menopausal women who took flibanserin experienced one “satisfying sexual event” more per month compared to those who took placebo, while a survey on the level of sexual desire gave it an advantage of 0.3 points on a scale of 5.
As in the 2010 trials, the pharmaceutical company Sprout Pharmaceuticals was behind the funding of the clinical trials sent to the FDA for authorisation of the drug; moreover, of the seven investigators, three were employees of the company and two were consultants.

Why are feminist organisations so interested in a drug with such low efficacy?

The controversy in the United States has been fuelled by feminist organisations such as “Even the Score”,5 which defends the “female Viagra” as a way of achieving equality in the pharmacological treatment of disorders that affect the sexual experience. Pressure from insufficiently informed feminist positions seems to promote the adoption of measures that contradict — as appears to be the case here — the scientific evidence. These pressures are undoubtedly behind the conclusions and recommendations of the FDA advisory committee that is now recommending its authorisation.
The aforementioned feminist platform has argued that 43% of women suffer dysfunctions in their sexual experience, implying that perhaps they could all benefit from the new treatment. Note that the expert opinion reflected in the aforementioned DSM-5 is diametrically opposed.
These assumptions will make the pharmaceutical sponsor of the new drug very happy, due to the hefty business that it will mean for them, but not, however, the potential users, who far from obtaining benefits in their treatment, will achieve little or no efficacy. They will however, gain numerous side effects, which in addition to those already mentioned include incompatibility with alcohol consumption and co-administration of a large number of medicines, and pregnancy (owing to the absence of data in this respect). Moreover, they face the uncertainty of a new treatment, administered daily for long periods of time, and about which little may be said of the results generated in the clinical trials, due to the short time period in which they were conducted.

   JUSTOAZNARPR03julio-tudela

Julio Tudela and Justo Aznar
Bioethics Observatory
Institute of Life Sciences
Catholic University of Valencia

References:

1 http://www.sproutpharma.com/
2 American Psychiatric Association. Highlights of changes from DSM-IV-TR to DSM-5.
2013. www.dsm5.org/Documents/changes%20from%20dsm-iv-tr%20to%20dsm-5.pdf.
3 Moynihan R. Evening the score on sex drugs: feminist movement or marketing masquerade?. BMJ 2014;349:g6246. doi: 10.1136/bmj.g6246 (Published 17 October 2014)
4 Moynihan R. Drug for low sexual desire carries significant harms, FDA advisers find. BMJ
2010;341:c3339.
5 http://eventhescore.org/