Research

Sexual performance research looks at how neuroendocrine, vascular, and emotional pathways shape libido, arousal, and erectile function. One of the most studied peptides here is PT-141 (bremelanotide), a melanocortin receptor agonist developed from Melanotan II. Unlike PDE5 inhibitors, which act peripherally on NO–cGMP signalling, PT-141 works centrally at melanocortin receptors (mainly MC4R) in the hypothalamus, modulating sexual desire and arousal. Phase 3 trials in women with hypoactive sexual desire disorder showed clinically meaningful improvements in sexual desire and distress scores with on-demand bremelanotide, while safety was acceptable over 24–52 weeks of use [1]. Earlier double-blind studies in men with erectile dysfunction reported significant, dose-dependent erectile responses after intranasal PT-141 vs placebo [2], and mechanistic work supports its role as a central melanocortin agonist for sexual dysfunction [3].

Melanotan II, the parent peptide, has been shown to induce penile erections and increase sexual desire in men with erectile dysfunction, again via melanocortin receptor activation rather than peripheral vasodilation. In controlled human studies, Melanotan II produced robust erectile responses and increased self-reported sexual desire compared with placebo, confirming that central melanocortin pathways can directly influence erectile physiology and motivation [4].

Beyond melanocortin signalling, kisspeptin and IGF-1 connect sexual performance with reproductive and vascular health. Kisspeptin, already central to reproductive hormone control, has been shown in human fMRI work to enhance limbic brain activity to sexual and couple-bonding stimuli and to reduce sexual aversion, highlighting its role in psychosexual and emotional aspects of libido [5]. At a vascular level, preclinical data show IGF-1 can restore erectile function in aged rats by improving corporal smooth muscle integrity and NO–cGMP signalling in the corpus cavernosum [6]. Together, these lines of research show how peptides can engage central arousal circuits, emotional–sexual processing, and peripheral erectile mechanisms.

References

1. Kingsberg SA, Clayton AH, Portman D, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: Two randomized phase 3 trials. Obstet Gynecol. 2019;134(5):899–908. PMID: 31599840

2. Diamond LE, Earle DC, Rosen RC, et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with erectile dysfunction. J Sex Med. 2004;1(2):193–203. PMID: 14963471

3. Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003;994:96–102. PMID: 12851303 

4. Wessells H, Hruby VJ, Hackett J, et al. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000;12 Suppl 4:S74–S79. PMID: 11035391

5. Comninos AN, Demetriou L, Wall MB, et al. Kisspeptin modulates sexual and emotional brain processing in humans. J Clin Invest. 2017;127(2):709–719. PMID: 28112678 

6. Pu XY, Wang HP, Zhang Y, et al. Insulin-like growth factor-1 restores erectile function in aged rats by improving the integrity of smooth muscle and nitric oxide–cyclic guanosine monophosphate signalling activity. BJU Int.2008;101(3):369–373. PMID: 18355170