In the first RCT of its kind, kisspeptin changed brain activity patterns and increased self-reported sexual feelings in 32 women with hypoactive sexual desire disorder.
32 womenThe first randomized placebo-controlled trial testing kisspeptin in women with diagnosed hypoactive sexual desire disorder, published in JAMA Network Open
What the researchers found
Kisspeptin administration significantly modulated sexual brain processing in women with HSDD — the first time this has been demonstrated in a clinical population. Specifically, kisspeptin deactivated the left inferior frontal gyrus (involved in behavioral inhibition) and activated the right postcentral and supramarginal gyrus during exposure to sexual stimuli.
Beyond brain imaging changes, kisspeptin produced measurable behavioral effects: women reported increased feelings of 'feeling sexy' compared to placebo. Increased activation of the posterior cingulate cortex with kisspeptin was associated with reduced sexual aversion — suggesting the peptide may help overcome the psychological barriers that characterize HSDD.
Why it matters
HSDD is the most common sexual dysfunction in women, yet there are very few approved treatments. This is the first RCT showing that kisspeptin — a peptide already known to influence sexual processing in men — can modulate the sexual brain circuits in women with clinically diagnosed low desire. The finding that kisspeptin reduced brain activity in inhibition-related areas while boosting self-reported sexual feelings suggests it works by releasing the 'brakes' on sexual desire rather than just pressing the 'accelerator.'
The numbers in context
n=32 · Premenopausal women with HSDD · Double-blind placebo-controlled crossover · Left inferior frontal gyrus deactivation · Right postcentral/supramarginal gyrus activation · Posterior cingulate cortex activation correlated with reduced aversion · Increased 'feeling sexy' scores
How the study worked
Thirty-two premenopausal women with diagnosed HSDD participated in a randomized, double-blind, placebo-controlled crossover trial. Each participant received both kisspeptin and placebo infusions on separate visits. Brain activity was measured using functional MRI while participants viewed sexual stimuli. Self-reported behavioral measures including feelings of sexiness and sexual aversion were collected.
Who was studied
32 premenopausal women with diagnosed hypoactive sexual desire disorder (HSDD)
What this study cannot tell us
Limited to premenopausal women — effects in postmenopausal women with HSDD are unknown. The single-session crossover design assessed acute effects only; whether repeated kisspeptin administration produces lasting changes in sexual desire is untested. Brain imaging changes during fMRI may not translate directly to improved sexual behavior in real-world settings. The study measured brain responses to stimuli in a scanner, not actual sexual experiences.
How to read the evidence
Strong evidence from a randomized, double-blind, placebo-controlled crossover trial published in JAMA Network Open. The crossover design provides robust within-subject comparisons. Limitations include the acute single-session design and the gap between brain imaging outcomes and real-world sexual behavior changes.
When this study was published
Published in 2022, this is a recent and landmark study that opens a new therapeutic direction for HSDD. Follow-up trials evaluating longer-term kisspeptin treatment are expected.
The bigger picture
The only FDA-approved drugs for HSDD — flibanserin (Addyi) and bremelanotide (Vyleesi) — have modest efficacy and notable side effects. Kisspeptin represents a fundamentally different approach: rather than targeting serotonin or melanocortin pathways, it works through the brain's reproductive hormone control system. Published in JAMA Network Open, this study establishes kisspeptin as a legitimate new therapeutic avenue for female sexual dysfunction and sets the stage for longer-term clinical trials.
Questions still open
- Would repeated kisspeptin administration over weeks produce sustained improvements in sexual desire, not just acute brain changes?
- Does kisspeptin work differently in postmenopausal women or women on hormonal contraceptives?
- Could kisspeptin be combined with existing HSDD treatments like bremelanotide for enhanced effects?
Common questions
What is HSDD and how common is it?
How is kisspeptin different from existing HSDD treatments?
Read the original research
Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.
JAMA network open, 5(10), e2237002
Citation
Mills, Edouard G; Sheridan, Rebecca; Byers, Alexander; Sherwood, Robin A; Alexander, Emma C; Bech, Paul; Wall, Matthew B; Mayneris-Perxachs, Jordi; Sherwood, Karolina; Sheridan, Alexander; Salem, Victoria; Owen, Benedict M; Clarke, Sophie A; Sheridan, Rupert; Sherwood, Robin; Dhillo, Waljit S. (2022). Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.. JAMA network open, 5(10), e2237002. https://doi.org/10.1001/jamanetworkopen.2022.37002