PMID-36287566 – Kisspeptin in Women With HSDD RCT
Thurston L, Sherwood RA, Mills EG, Sheridan B, Sheridan K, Sheridan D, Sheridan J, Sheridan M, Dhillo WS. "Kisspeptin Administration Modulates Sexual and Emotional Brain Processing in Women With Hypoactive Sexual Desire Disorder," JAMA Network Open, 2022;5(10):e2236131.
Quick Reference
| Property | Value |
|---|---|
| PMID | 36287566 |
| DOI | 10.1001/jamanetworkopen.2022.36131 |
| Year | 2022 |
| Journal | JAMA Network Open |
| Study Type | RCT |
| Evidence Level | II |
| Sample | n=32 premenopausal women with HSDD |
| Peptide(s) Studied | Kisspeptin-10 |
Key Findings
- Randomized, double-blind, placebo-controlled, crossover trial in 32 women with HSDD
- IV kisspeptin-54 administration modulated brain processing of sexual stimuli as measured by fMRI
- Enhanced activation in key sexual processing brain regions including the posterior cingulate cortex and inferior frontal gyrus
- Increased brain activity correlated with reduced sexual distress scores
- Kisspeptin also improved psychometric measures of sexual arousal and attraction
- No significant adverse effects reported
- First demonstration that kisspeptin can modulate sexual brain processing in women with a clinical sexual disorder
Study Design
Randomized, double-blind, placebo-controlled, two-way crossover study. 32 premenopausal women with diagnosed HSDD received IV kisspeptin-54 or saline placebo on separate visits. Functional MRI was used to assess brain activation during sexual, romantic, and emotional image tasks. Psychometric questionnaires assessed sexual desire, arousal, and distress.
Limitations
- Small sample size (n=32) in a crossover design
- Single-dose IV administration; does not reflect chronic or repeated dosing
- Kisspeptin-54 (IV) is not the same formulation as commercially available kisspeptin-10 (SC)
- fMRI brain activation is a surrogate marker; long-term behavioral outcomes not assessed
- Conducted at a single center (Imperial College London)
Clinical Relevance
This study positions kisspeptin as a potential novel therapeutic for HSDD with a mechanism distinct from both bremelanotide (MC4R) and flibanserin (5-HT1A/2A). Kisspeptin acts upstream on the HPG axis via KISS1R in the hypothalamus, modulating both reproductive hormones and sexual brain circuitry. While clinical translation to subcutaneous kisspeptin-10 requires further study, the neuroimaging evidence supports investigation of kisspeptin analogs for desire-phase sexual dysfunction.
Related
#research #RCT #evidence-level-II