Flibanserin can cause weight loss in pre/postmenopausal women with HSDD

Premenopausal and postmenopausal women treated with the combined agonist/antagonist flibanserin for hypoactive sexual desire disorder (HSDD) are likely to lose weight, according to a post hoc analysis of five studies.

“It is very reassuring to know that women taking flibanserin do not need to be concerned about weight gain as a side effect of treatment, and in fact may lose a significant amount of weight while taking the medication,” says lead author Susan Kornstein, MD, a professor of psychiatry and obstetrics/gynecology at Virginia Commonwealth University (VCU) in Richmond and executive director of the VCU Institute for Women's Health.

The analysis, which appears in the Journal of Women’s Health, was undertaken because a side effect of weight gain often makes women reluctant to use a medication. “Because flibanserin modulates serotonin, like some antidepressants, there was concern that the drug could lead to weight gain,” Dr. Kornstein told Contemporary OB/GYN.

Concern arose because flibanserin is a minor 5-HT2C receptor antagonist, and “the 5-HT2C agonist lorcaserin has been approved by the FDA as a weight loss drug,” Dr. Kornstein says. “Thus, one might have expected flibanserin to cause weight gain rather than weight loss. This suggests that the observed weight loss in this analysis is unlikely to be caused by the serotonin-related activity of flibanserin.”

For the five studies combined, the mean weight at baseline was about 73 kg (161 lbs). “A weight loss of at least 5% of baseline body weight at 24 weeks would be a weight loss of at least 3.6 kg (8 lbs), which occurred in 21% of the women on flibanserin versus 7.8% of those on placebo,” Dr. Kornstein says. These findings are in contrast to trials of FDA-approved weight-loss medications, where the average weight loss has been 5 kg to 10 kg for the active drug versus 1 kg to 3 kg for placebo, according to Dr. Kornstein.

“It is important to note, however, that those trials were conducted in obese patients, 70% to 85% of whom were women,” Dr. Kornstein says. “The trials also included dietary and exercise counseling in addition to medication.”

In the flibanserin HSDD studies, on the other hand, “the women were not selected for overweight or obesity, and they did not receive dietary or exercise counseling as part of the studies,” Dr. Kornstein says.

Furthermore, weight loss as little as 5% has been associated with significant improvements in health and weight-related comorbidities, including hypertension, elevated cholesterol and type 2 diabetes.

“The exact mechanism by which flibanserin produces weight loss is unknown,” Dr. Kornstein says. “It may affect body weight via a serotonin-based process or perhaps via a non-serotonin-related mechanism, such as enhanced cortical norepinephrine or dopamine release.”

Dr. Kornstein notes that the melanocortin 4 receptor, which can be impacted by dopamine release, has been linked to both weight and sexual control mechanisms. “Interestingly, we found no association between weight loss and HSDD treatment response, suggesting that the mechanism of action for weight loss may differ from that for improving sexual function,” she says. 

The investigators also looked specifically at whether nausea was a contributor to weight loss. But the incidence of nausea in premenopausal women who received flibanserin in the three 24-week studies was actually higher among women with weight loss less than 5% compared to women with weight loss of 5% or greater: 7.1% and 5.8%, respectively.

Abstaining from alcohol was also not a factor in the weight loss because women in the studies were allowed to drink alcohol.