An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist

This pioneering study evaluated the effect of bremelanotide (PT-141), a melanocortin receptor agonist, on subjective sexual response in women with sexual arousal disorder. Using a double-blind, placebo-controlled crossover design, 18 premenopausal women diagnosed with female sexual arousal disorder received intranasal bremelanotide 20 mg or placebo in separate sessions.

Sexual response was assessed through validated questionnaires and physiological measures during exposure to visual sexual stimuli. Results demonstrated that bremelanotide produced a significant increase in sexual desire and subjective arousal compared to placebo.

Key findings:

• Significant improvement in subjective sexual desire and arousal scores
• The effect occurred through a central (CNS) mechanism, not peripheral
• The intranasal route provided rapid absorption and relatively early onset
• The safety profile was acceptable, with nausea as the main adverse effect

This study was significant as one of the first to demonstrate that an agent acting on melanocortin receptors in the central nervous system can improve female sexual function. Unlike peripheral vasoactive agents (such as sildenafil), bremelanotide acts on the neural circuitry of desire, representing a fundamentally different mechanism of action. These preliminary findings were essential for subsequent development that culminated in the phase 3 RECONNECT trials and the FDA approval of bremelanotide (Vyleesi) for the treatment of hypoactive sexual desire disorder in premenopausal women.