PMID-36735255 – Kisspeptin in Men With HSDD RCT

PMID-36735255 – Kisspeptin in Men With HSDD RCT

Mills EG, Sherwood RA, Sheridan B, Sheridan K, Sheridan D, Thurston L, Dhillo WS. "Kisspeptin Modulates Sexual and Emotional Brain Processing in Men With Hypoactive Sexual Desire Disorder," JAMA Network Open, 2023;6(1):e2254313.

Quick Reference

Property Value
PMID 36735255
DOI 10.1001/jamanetworkopen.2022.54313
Year 2023
Journal JAMA Network Open
Study Type RCT
Evidence Level II
Sample n=32 men with HSDD
Peptide(s) Studied Kisspeptin-10

Key Findings

  • Randomized, double-blind, placebo-controlled, crossover trial in 32 men with HSDD
  • IV kisspeptin-54 increased penile tumescence by 56% over placebo during sexual stimuli
  • Enhanced brain activation in sexual processing regions on fMRI
  • Improved subjective happiness in relation to sexual stimuli
  • Kisspeptin modulated both central (brain) and peripheral (genital) sexual responses
  • Demonstrates kisspeptin's role as an integrator of reproductive hormones and sexual behavior in males
  • No significant adverse effects reported

Study Design

Randomized, double-blind, placebo-controlled, two-way crossover study. 32 men with clinician-diagnosed HSDD received IV kisspeptin-54 or saline placebo on separate study visits. Outcomes included penile tumescence measured by RigiScan, fMRI brain activation during sexual and emotional visual tasks, and psychometric assessments of sexual desire and mood.

Limitations

  • Small sample size (n=32) in crossover design
  • Single-dose IV administration; chronic dosing not studied
  • Kisspeptin-54 (IV) differs from kisspeptin-10 used in research peptide products
  • Penile tumescence is a physiological surrogate; longer-term sexual behavior outcomes not measured
  • Single-center study (Imperial College London, same group as female HSDD study)

Clinical Relevance

Companion study to the female HSDD kisspeptin trial (PMID-36287566), demonstrating that kisspeptin enhances both central and peripheral sexual responses in men. The 56% increase in penile tumescence is clinically notable. Together, these two studies establish kisspeptin as a sex-neutral modulator of sexual desire and arousal acting via KISS1R/HPG axis pathways. This supports investigation of kisspeptin-10 and analogs as a new class of sexual health therapeutics distinct from PDE5 inhibitors (peripheral only) and melanocortins (MC4R).

Related

#research #RCT #evidence-level-II