Hypoactive
sexual desire disorder (HSDD) is defined as “persistently or recurrently
deficient (or absent) sexual fantasies and desire for sexual activity”
accompanied by “marked distress and interpersonal difficulty” that is not
accounted for by a nonsexual mental disorder, medication, severe relationship
stress, or a general medical condition. In 2013, HSDD was replaced in the DSM5
by a new diagnosis called female sexual interest/arousal disorder (FSIAD).
In
August 2015, the United States FDA approved the first and only medical
treatment for HSDD in premenopausal women: flibanserin, sold under the trade
name Addyi. Flibanserin is a 5HT1A receptor agonist, 5HT2A receptor antagonist,
and D4 receptor partial agonist that was originally developed as an
antidepressant. While it did not show efficacy in that department, it was found
to have a favorable effect on female sex drive in post-hoc analysis. Because dopamine and norepinephrine are
thought to promote sexual desire and arousal while serotonin is thought to
inhibit sexual desire and arousal, flibanserin was thought to enhance sexual
desire in HSDD by increasing levels of dopamine and norepinephrine and
decreasing levels of serotonin.
The
approval of flibanserin has been met with much controversy surrounding its
efficacy and safety. The FDA denied approval twice, in 2010
and 2013, before its third submission by Sprout Pharmaceuticals in 2015. Approval was based on the outcomes of
three clinical trials that studied number of sexually satisfying events (SSEs) that
patients experienced per month. Compared to placebo, improvements were variable
across trials. Jaspers et al (2016) conducted a systematic review and
meta-analysis of studies assessing efficacy and safety of flibanserin for the
treatment of women with HSDD. They ultimately included 8 studies that included
over 6000 women. All were randomized,
double-blind, placebo-controlled trials. All studies included premenopausal or
postmenopausal women with acquired HSDD according to the DSM4 definition, and
for whom the diagnosis was ascertained by a trained clinician via a diagnostic
interview. All women were in stable, heterosexual, monogamous relationships for
at least 1 year. Most studies included a dosing regimen of 100 mg of
flibanserin once daily at bedtime.
Results showed that flibanserin has
limited clinical efficacy. It increased the number of reported SSEs from
baseline by about 0.5 episodes per month compared to placebo, and subjectively
flibanserin users and controls reported minimal meaningful improvement.
Meanwhile, data showed a significant 2-4 times increased risk of adverse
effects. The main side effects of flibanserin are as follows:- Boxed warning: hypotension and syncope
- Contraindicated with alcohol, strong or moderate CYP3A4 inhibitors, and hepatic impairment of any degree
- CNS depression (somnolence, sedation, fatigue)
- Dizziness, nausea
I have concerns about the adverse
effects of flibanserin especially when combined with alcohol and its potential
to be abused by rapists.
Furthermore, studies of flibanserin
excluded many women: those taking a wide range of medications, those with a
wide range of diseases, and those not in a “stable, communicative,
heterosexual” relationship. Participants also had to be willing to engage in
sexual activity at least once a month to even be eligible to participate in the
studies. Therefore, it is impossible to know the actual base rate of SSEs in
women with HSDD, and likely that the patient population in these studies is not
representative of typical HSDD patients. The authors of this review recommend
that, before flibanserin can be recommended in guidelines and clinical
practice, future studies should include women from diverse populations,
particularly women with a history of somatic and psychological comorbidities,
medication use, and surgical menopause. They also recommend an integrative
approach to HSDD that addresses medical, psychiatric, psychological,
couple-relationship, and sociocultural elements of sex.
There
is also controversy surrounding the idea of HSDD (or FSAID) itself as a medical
issue in need of being treated.
Many that
supported the development of flibanserin maintain that HSDD is a very common
and underdiagnosed problem that can have a profound effect on women’s quality
of life. This was emphasized in 14 Continuing Medical Education modules on HSDD
in women available for healthcare providers, all of which disclosed funding
through educational grants by Boehringer Ingelheim, the pharmaceutical company
that had originally developed flibanserin as a failed antidepressant and was
working to have it approved in 2010. Included in this CME module was the message that “a major barrier to clinicians talking about
hypoactive sexual desire disorder/female sexual dysfunction is the lack of
medications”. After being sold to
Sprout Pharmaceuticals, and after its second rejection by the FDA, the company
launched a public relations campaign persuading several women’s groups, female
Congressional representatives, and a group of clinicians to advocate that it is
problematic that there are medications like Viagra available to treat sexual
problems for men, but not women (Meixel, Yanchar, Fugh-Berman, 2015). The message was that, as usual, women’s desire for sexual
pleasure is minimized and their lived experiences ignored, and that this is to
deny treatment for women who are in distress. This was part of what convinced
the FDA to finally approve filbanserin in 2015.
On the
other hand, this medication is not the equivalent to Viagra. Viagra treats the
physiologic condition of erectile dysfunction by increasing blood flow to the
penis, but it does not do anything to affect sexual arousal or desire in those
with penises. In fact, there have been no studies of the impact of flibanserin
in men’s sexual arousal. Why might this be? I won’t even begin to get into the
problems with the entirety of the conversation surrounding HSDD being based on
the heteronormativity of cis heterosexual relationships and ignoring the full
spectrum of gender, sexuality, and desire, but it is telling that this
medication is only being marketed to increase women’s sexual desire.
The CME modules on HSDD also go on to state the following:
- Women who have HSDD will express frustration, anger, diminished self-esteem, a sense of hopelessness, and a sense of decline in their femininity
- Women may not always be aware that they have a sexual dysfunction, and often present with the complaint of loss of desire without awareness of the complexity of the concept
- A woman previously had sexual desire for her current partner but now lacks sexual interest in that individual, although she still has desire for sexual stimulation alone or with someone other than her present partner, still qualifies for a diagnosis of “situational HSDD”
- A woman who is happy with her sex life may still qualify for a diagnosis of hypoactive sexual desire disorder if her partner is dissatisfied, because of “marked interpersonal difficulties with her husband because of her reduced interest in sex”
I
believe that the diagnosis of HSDD and marketing of filbanserin runs the risk
of unnecessarily pathologizing the normal spectrum of human sexuality. There is
no scientifically established norm for sexual activity or desire. What should
be considered the standard of “normal” and “healthy”? Once a month, once a
week, daily? What kind of sex are we talking about and what makes it count as
satisfying? Because interest in sex can be influenced by so many things—life
stress, fatigue, relationship, illness, medication, depression—I wonder if it
is really plausible that we can separate all of that away and truly diagnose HSDD
as an intrinsic disorder. In fact, the screening tool that healthcare providers
use to identify HSDD, the five-question Decreased Sexual Desire Screener, was
developed and validated by the company Boehringer Ingelheim before
being distributed to the medical community.
To me,
pathologizing decreased interest in sex feels like convincing women that they
should always want to have sex in the
context of heterosexual relationships, and if they don’t then there must be
something wrong with them—or their femininity, as the CME module suggested—that must be fixed. It emphasizes
that even if women do not perceive a problem, if their partner does then that
must be fixed. It also suggests to women and their physicians (the CME module
states that “providers
were frustrated by the lack of easy and uncomplicated treatment options for
HSDD”) that
decreased desire for sex is an issue that can and should be addressed primarily
through medication, rather than through a more multidimensional approach that
may include sex therapy, relationship counseling, and lifestyle changes.
However,
hyping HSDD as a medical problem affecting millions of women does conveniently create
a market for the pharmaceutical industry to sell flibanserin. Everybody wins,
right? Oh, except that the drug has not actually shown any substantial evidence
of efficacy and has a profound side effect profile. In conclusion, I am
skeptical, and worry that flibanserin is nothing more than a scam by the
pharmaceutical industry to profit off of persuading women that they need to be
having sex when they don’t actually want to.
Natalie DiCenzo DUCOM 2020
Sources:
Jaspers et al, 2016. Efficacy and
safety of flibanserin for the treatment of hypoactive sexual desire disorder in
women: a systemic review and meta-analysis. JAMA
Internal Med. 176 (4): 453-462.
Meixel A, Yanchar E, Fugh-Berman A. 2015. Hypoactive sexual
desire disorder: inventing a disease to sell low libido. Journal of Medical Ethics (41)
:859-862.
