2019 Update on female sexual dysfunction
The recent FDA approval of bremelanotide (Vyleesi) will give clinicians an additional option for treating premenopausal women with HSDD. In this Update, Dr. Barbara Levy explores the drug’s efficacy, dosing, and adverse effects with Dr. Sheryl Kingsberg, one of the investigators involved in the bremelanotide clinical trials, and discusses how this medication differs from flibanserin.
Clinical trials show bremelanotide improves desire, reduces distress
Two phase 3 clinical trials, dubbed the Reconnect studies, demonstrated that, compared with placebo, bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress regarding sexual desire.
The 2 identical, randomized, placebo-controlled multicenter trials included 1,247 premenopausal women with HSDD of at least 6 months' duration.9,12 Bremelanotide 1.75 mg (or placebo) was self-administered subcutaneously with an autoinjector on an as-desired basis. The 24-week double-blind treatment period was followed by a 52-week open-label extension study.
The co-primary efficacy end points were the change from baseline to end-of-study (week 24 of the double-blind treatment period) in the 1) Female Sexual Function Index (FSFI) desire domain score and 2) feeling bothered by low sexual desire as measured by Question 13 on the Female Sexual Distress Scale (FSDS). An increase in the FSFI desire domain score over time denotes improvement in sexual desire, while a decrease in the FSDS Question 13 score over time indicates improvement in the level of distress associated with low sexual desire.
In the 2 clinical studies, the mean change from baseline (SD) in the FSFI desire domain score, which ranged from 1.2 to 6.0 at study outset (higher scores indicate greater desire), was:
- study 1: 0.5 (1.1) in the bremelanotide-treated women and 0.2 (1.0) in the placebo-treated women (P = .0002)
- study 2: 0.6 (1.0) in the bremelanotide group versus 0.2 (0.9) in the placebo group (P<.0001).
For FSDS Question 13, for which the score range was 0 to 4 (higher scores indicate greater bother), the mean change from baseline score was:
- study 1: -0.7 (1.2) in the bremelanotide-treated group compared with -0.4 (1.1) in the placebo-treated group (P<.0001)
- study 2: -0.7 (1.1) in the bremelanotide group and -0.4 (1.1) in the placebo group (P = .0053).
It should be noted that, in the past, SSEs were used as a primary end point in clinical studies. However, we have shifted from SSEs to desire and distress as an end point because SSEs have little to do with desire. Women worry about and are distressed by the fact that they no longer have sexual appetite. They no longer "want to want" even though their body will be responsive and they can have an orgasm. That is exemplified by the woman in our case scenario (see box, page 18), who very much wants the experience of being able to anticipate with pleasure the idea of having an enjoyable connection with her partner.
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