Bremelanotide (Vyleesi): Uses, Evidence, and Side Effects

For premenopausal women whose low sexual desire causes real distress, treatment options have been limited. Bremelanotide, sold as Vyleesi, is one of the few FDA-approved medications developed specifically for this concern.

Key takeaways

• Bremelanotide (Vyleesi) is approved for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.
• It works as a melanocortin receptor agonist, acting mainly on MC1R and MC4R at therapeutic doses.
• It is not approved for HSDD in postmenopausal women or in men, and is not intended to enhance sexual performance.
• At least 10 clinical trials have studied bremelanotide, including completed Phase 2 and Phase 3 trials.
• The most frequently reported adverse events in FAERS data are nausea, headache, and vomiting.

What Bremelanotide Is

Bremelanotide belongs to a class of compounds called melanocortin receptor agonists. It nonselectively activates several melanocortin receptor subtypes, with the greatest potency at MC1R, followed by MC4R, MC3R, MC5R, and MC2R. At the doses used in treatment, activity at MC1R and MC4R is considered most relevant. MC4R-expressing neurons are found throughout the central nervous system, but the exact way bremelanotide improves HSDD symptoms is not fully understood.

What Bremelanotide Is Approved For

Under the brand name Vyleesi, bremelanotide is approved to treat acquired, generalized HSDD in premenopausal women. Acquired HSDD means the low desire developed after a period of normal sexual interest, while generalized means it occurs across situations and partners rather than in specific circumstances. The label specifies that this diagnosis excludes low desire caused by a coexisting medical or psychiatric condition, relationship problems, or medication effects. Vyleesi is not indicated for postmenopausal women, for men, or for enhancing sexual performance. The label does not carry a boxed warning.

What the Evidence Shows

Bremelanotide has been evaluated in at least 10 registered clinical trials. A completed Phase 2 trial examined its safety and efficacy in women with female sexual arousal disorder. A completed Phase 3 trial assessed its efficacy and safety specifically in premenopausal women with HSDD, supporting the eventual approval. A completed Phase 4 trial also measured bremelanotide concentrations in the breast milk of lactating women after a single dose.

Reported Side Effects

Adverse event reports submitted to FAERS reflect counts of reported reactions, not confirmed rates of incidence or proof that bremelanotide caused the event. The most commonly reported reaction is nausea, followed by headache and vomiting. Reports of flushing also appear, consistent with the drug's receptor activity. Other reported terms include drug ineffectiveness, off label use, general illness, and adverse drug reaction, which reflect how the event was characterized rather than a specific physical symptom.