Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.

Thurston L, Hunjan T, Ertl N, Wall MB, Mills EG, Suladze S, Patel B, Alexander EC, Muzi B, Bassett PA, Rabiner EA, Bech P and 4 more

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Goldmeier D, Abbara A, Comninos AN, Dhillo WS

JAMA network open3 Oct 2022Cited by 27 (Europe PMC)

PMID36287566PMCIDPMC9606846DOI10.1001/jamanetworkopen.2022.36131PepBankPUB-36287566

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Summary

ImportanceDespite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown.ObjectiveTo test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD.Design, setting, and participantsThis randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021.InterventionsA 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.Main outcomes and measuresBlood oxygen level-dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli.ResultsOf the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin's enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects.Conclusions and relevanceThese findings lay the foundations for clinical applications for kisspeptin in women with HSDD.Trial registrationISRCTN trial registry identifier: ISRCTN17271094.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanRandomized controlled trialEfficacy outcome
In premenopausal women with HSDD, kisspeptin‑54 infusion deactivated the left inferior frontal gyrus during sexual and facial attraction processing versus placebo.
In plain wordsIn women with low sexual desire, kisspeptin changed activity in the left inferior frontal gyrus during sexual and attractiveness tasks compared with placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseLeft inferior frontal gyrus response to sexual and facial attraction stimuli
Study
n = 32
Comparator
Placebo infusion
Analysis
Primary
Outcome group
Sexual function · Nervous system and cognition
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Measurements
Z max
3.76 Z
left inferior frontal gyrus
Source sentences
Summary
Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02).
2 context sentences(design, population, supporting numbers)
Summary · context
This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover.
Summary · context
A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.
Show in the study text Report a problemFND-3628756601
02HumanRandomized controlled trialEfficacy outcome
In premenopausal women with HSDD, kisspeptin‑54 infusion activated the right postcentral and supramarginal gyrus during sexual and facial attraction processing versus placebo.
In plain wordsIn women with low sexual desire, kisspeptin increased activity in the right postcentral and supramarginal gyrus during sexual and attractiveness tasks compared with placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseRight postcentral and supramarginal gyrus response to sexual and facial attraction stimuli
Study
n = 32
Comparator
Placebo infusion
Analysis
Primary
Outcome group
Sexual function · Nervous system and cognition
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Measurements
Z max
3.73 Z
right postcentral and supramarginal gyrus
Source sentences
Summary
Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02).
2 context sentences(design, population, supporting numbers)
Summary · context
This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover.
Summary · context
A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.
Show in the study text Report a problemFND-3628756602
03HumanRandomized controlled trialEfficacy outcome
In premenopausal women with HSDD, kisspeptin‑54 infusion deactivated the right temporoparietal junction during sexual and facial attraction processing versus placebo.
In plain wordsIn women with low sexual desire, kisspeptin changed activity in the right temporoparietal junction during sexual and attractiveness tasks compared with placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseRight temporoparietal junction response to sexual and facial attraction stimuli
Study
n = 32
Comparator
Placebo infusion
Analysis
Primary
Outcome group
Sexual function · Nervous system and cognition
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Measurements
Z max
4.08 Z
right temporoparietal junction
Source sentences
Summary
Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02).
2 context sentences(design, population, supporting numbers)
Summary · context
This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover.
Summary · context
A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.
Show in the study text Report a problemFND-3628756603
04HumanRandomized controlled trialMechanism
In women with HSDD, kisspeptin-enhanced hippocampal activity in response to erotic videos correlated positively with baseline distress relating to sexual function.
In plain wordsIn women with low sexual desire, a larger kisspeptin-linked rise in hippocampal activity to erotic videos went with more baseline sexual distress.
Peptide
Kisspeptin-54 (metastin)
Outcome
Not applicableCorrelation of kisspeptin-enhanced hippocampal activity with baseline sexual distress
Study
n: not reported in source
Outcome group
Sexual function · Nervous system and cognition
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Measurements
r
0.469
hippocampal activity vs baseline distress
Source sentences
Summary
Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007).
2 context sentences(design, population, supporting numbers)
Summary · context
This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover.
Summary · context
A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.
Show in the study text Report a problemFND-3628756604
05HumanRandomized controlled trialMechanism
In women with HSDD, kisspeptin-enhanced posterior cingulate cortex activity in response to attractive male faces correlated with reduced sexual aversion.
In plain wordsIn women with low sexual desire, a larger kisspeptin-linked rise in posterior cingulate activity to attractive male faces went with less sexual aversion.
Peptide
Kisspeptin-54 (metastin)
Outcome
Not applicableCorrelation of kisspeptin-enhanced posterior cingulate cortex activity with sexual aversion
Study
n: not reported in source
Outcome group
Sexual function · Nervous system and cognition
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Measurements
r
0.476
posterior cingulate cortex activity vs sexual aversion
Source sentences
Summary
Kisspeptin's enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005).
2 context sentences(design, population, supporting numbers)
Summary · context
This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover.
Summary · context
A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.
Show in the study text Report a problemFND-3628756605
06HumanRandomized controlled trialSafety outcome
In women with HSDD, kisspeptin‑54 infusion was well tolerated, with no reported adverse effects.
In plain wordsIn women with low sexual desire, kisspeptin infusion was well tolerated and no adverse effects were reported.
Peptide
Kisspeptin-54 (metastin)
Outcome
No significant changeAdverse effects
Study
n: not reported in source
Comparator
Placebo infusion
Outcome group
Adverse events · Whole body
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Source sentences
Summary
Kisspeptin was well-tolerated with no reported adverse effects.
2 context sentences(design, population, supporting numbers)
Summary · context
This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover.
Summary · context
A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.
Show in the study text Report a problemFND-3628756606

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Version history

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Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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