A systematic review of the use of bupropion for hypoactive sexual desire disorder in premenopausal women

Objective: To assess the efficacy of bupropion therapy for hypoactive sexual desire disorder (HSDD) in women. Methods: A systematic review was performed utilizing the standard databases. Data were abstracted for study quality, characteristics, and outcomes. Due to the small number of studies and lack of consistently reported outcomes, a meta-analysis was not performed. Results: Two studies (289 women) met inclusion criteria. While one study had low risk of bias, the other had areas of high risk of bias. Both trials reported improvement in sexual function domains with treatment ranging from 12 weeks to 112 days. Conclusions: Despite two trials demonstrating benefit with bupropion treatment for premenopausal women with HSDD, the evidence is limited and not of adequate quality to recommend the therapy. More trials are needed in this area. Corresponding author: David M. Haas, MD, MS, Dept. of OB/GYN, , 550 N University Blvd, , UH 2440, Indianapolis, IN 46202, (317)880-3959 (office), dahaas@iupui.edu


INTRODUCTION
Female sexual dysfunction is a prevalent problem worldwide with reported rates of 10-30% 1-3 .
Hypoactive sexual desire disorder (HSDD) is a common form of sexual dysfunction affecting females more often than males at rates of 30% and 15%, respectively 2,4 .
HSDD is defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as "the persistent or recurrent deficiency or absence of sexual fantasies/thought, and/or desire for sexual activity that causes personal distress or interpersonal difficulties" 5 . It is not uncommon for women with HSDD to also have concomitant sexual arousal and/or orgasmic disorders 6 . Additionally, HSDD and low sexual desire in general are believed to be underestimated by health care providers and are associated with decreased relationship satisfaction and distress for many women and their partners 1,7 . Furthermore, impaired sexual desire has been shown to be associated with depressed mood. While studies have shown improvement in sexual function with relief of depressive symptoms, additional investigation into the psychological and physiological effects of antidepressants has provided evidence of antidepressant-induced sexual dysfunction as an adverse effect of many of these medications 8 . Despite ongoing research into female sexual dysfunction and HSDD, the exact etiology of these disorders is yet to be determined.
There have been many trials conducted to determine the efficacy of various therapies in the treatment of HSDD. Decreased androgen levels have been shown to be associated with a decline in libido.
Testosterone therapy (oral, transdermal patch, or topical) has been investigated through randomized controlled trials (RCTs) indicating statistically significant improvement in sexual desire 1  Bupropion is a centrally-acting medication that is currently approved for use in the treatment of major depressive disorder, seasonal affective disorder, and smoking cessation (Bupriopion package insert 2014).
The exact mechanism of action of bupropion has yet to be determined, however, it is believed to act centrally on both dopaminergic and norepinephrine systems with no serotonergic action 8 . In addition to its role in mood improvement, bupropion has been shown to be effective in the reversal of SSRI-induced sexual dysfunction when supplemented to current therapy as well as a substitution therapy [9][10][11] . In addition to treatment of iatrogenic sexual dysfunction, study results indicate prosexual effects through the use of bupropion 12, 13 .
The objective of this study was to systematically review

METHODS
This was a systematic review of randomized controlled trials. We searched the terms "psychological sexual dysfunction," "physiological sexual dysfunction," "libido," "hypoactive sexual desire disorder," and  arm. We planned to perform a meta-analysis on the identified RCTs but were unable to as the outcomes presented in the identified trials were not reported in a way that allowed for combining. We attempted to contact the trial authors to obtain additional data but did not receive responses.

Trials included
Only 2 trials met inclusion criteria (

Discussion
This systematic review of RCTs reporting the use of bupropion for HSDD in premenopausal women discovered only 2 eligible trials on the topic. Both trials reported that bupropion was an effective and welltolerated treatment for HSDD in premenopausal women.
However, mainly due to potential bias with the Segraves trial and inability to contact the authors to obtain more granular trial data, we were unable to perform a metaanalysis. This systematic review was limited by the lack of RCTs in this area. It is possible that we failed to find a trial on the topic. However, our search strategy and additional searches of reference lists and clinicaltrials.gov are standard means to find other studies. It is unlikely that large, high-quality trial data were missed with our search strategy. We were also unable to contact the Segraves study authors to obtain more detailed data. Thus we were unable to perform a meta-analysis on the commonly reported BISF-W domains. As both trials reported benefit for these domains, combining the data may have strengthened the conclusions of benefit.
As HSDD is a common yet complex problem, multiple solutions have been tested. Based on the data and statistical analysis of these 2 trials, the use of bupropion in premenopausal women with HSDD may be effective in improving sexual dysfunction symptoms, leading to overall improved sexual satisfaction.
Treatment of HSDD in premenopausal women with bupropion may hold potential to help women suffering from this condition. More studies are needed to better understand the beneficial impact of the treatment and the potential side effects, particularly with prolonged use. Organizing research resources around this issue that impacts many women and their partners is important. Given the results of this systematic review, there may be potential for bupropion to be used as a treatment for HSDD in premenopausal women.