PT-141 vs Kisspeptin-10
PT-141, or bremelanotide, is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone that agonises melanocortin receptors, and it was approved in 2019 for generalised acquired hypoactive sexual desire disorder in premenopausal women. Kisspeptin-10 is the C-terminal decapeptide of the KISS1 gene product and an agonist at the kisspeptin receptor, an investigational compound whose primary role in the literature is as a regulator of gonadotropin-releasing hormone secretion, with a smaller and more recent line of work on sexual and emotional brain processing. Both are marketed for libido, which is why they are set side by side. No study has administered both to the same subjects, and the two act at unrelated receptor families. The publications that engage both come from a single research group in London that has run separate trials of each, plus a 2026 survey of peptide availability in sexual medicine and preclinical work on how melanocortin and kisspeptin circuits interact.
No study has compared them directly.
Everything below is drawn from separate studies that used different models, endpoints and species. That is a real limit on what can be concluded, not a formality.
No published study has administered bremelanotide and kisspeptin to the same participants, and no trial has compared them against each other. The closest the literature comes is a pair of trials run by the same group at Imperial College London and published in the same month of 2022, each with a placebo comparator and neither with the other compound as an arm. In one, thirty-one premenopausal women with hypoactive sexual desire disorder received a melanocortin 4 receptor agonist in a randomised, double-blinded, placebo-controlled crossover design with functional neuroimaging; in the other, thirty-two premenopausal women with the same diagnosis received kisspeptin under the same design. Both reported changes in sexual brain processing relative to placebo, but the imaging regions, the stimuli and the analyses differ, so the two results cannot be placed on a common scale. An important asymmetry sits inside that pairing: the kisspeptin trial used kisspeptin-54, the longer isoform, rather than the decapeptide sold as kisspeptin-10. Beyond those trials, a 2026 survey of peptide availability in sexual medicine tabulates both compounds with their mechanisms, indications, regulatory status and adverse effects; a physiological review and a pharmacology compendium name both; and preclinical work reports that melanocortin agonism activates kisspeptin neurons in the preoptic area of the sheep, which describes an interaction between the two systems rather than a comparison between the two drugs.
The 8 publications that cover both
- 01Review2026
Access without approval: state-level determinants of peptide availability in sexual medicine
Quesada SG, et al. · Sexual Medicine · review of peptides used in sexual medicine and of the regulatory determinants of their availability, tabulating bremelanotide, kisspeptin, growth hormone releasing peptides, oxytocin and BPC-157
The authors reported that bremelanotide was the only one of the peptides examined with an approved sexual medicine indication, described as a melanocortin receptor agonist increasing dopamine release and consequently sexual desire, approved for hypoactive sexual desire disorder in premenopausal women and prescribable off-label. Kisspeptin was recorded on the United States regulator's category 2 list of bulk drug substances, indicating no or only limited safety information, with the adverse-effect column stating that it remained in human clinical trials and that no adverse events had been published.
- 02Human clinical2022
Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder
Thurston L, et al. · The Journal of Clinical Investigation · randomised, double-blinded, placebo-controlled crossover study with psychometric, functional neuroimaging and hormonal analyses in 31 premenopausal heterosexual women with hypoactive sexual desire disorder (NCT04179734)
Melanocortin 4 receptor agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. On functional neuroimaging it enhanced cerebellar and supplementary motor area activity, deactivated the secondary somatosensory cortex in response to visual erotic stimuli, and enhanced functional connectivity between the amygdala and the insula. The authors interpreted the pattern as reduced self-consciousness, increased sexual imagery and sensitisation to erotic stimuli. The agent used was bremelanotide, supplied by its manufacturer.
- 03Human clinical2022
Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial
Thurston L, et al. · JAMA Network Open · double-masked, placebo-controlled two-way crossover randomised clinical trial of intravenous kisspeptin-54 versus placebo, 40 randomised and 32 premenopausal women with hypoactive sexual desire disorder completing both visits, with functional neuroimaging, psychometric and hormonal analyses
Kisspeptin administration modulated sexual and facial attraction brain processing, with deactivation of the left inferior frontal gyrus and right temporoparietal junction and activation of the right postcentral and supramarginal gyrus. Kisspeptin-enhanced hippocampal activity in response to erotic videos correlated with baseline sexual distress, and enhanced posterior cingulate cortex activity correlated with reduced sexual aversion. Kisspeptin was well tolerated with no reported adverse effects. In the introduction the authors described bremelanotide and flibanserin, the two licensed treatments in the United States, as limited by adverse-effect burden and effectiveness.
- 04Review2025
Kisspeptin and neurokinin B: roles in reproductive health
Koysombat K, et al. · Physiological Reviews · comprehensive physiological review of kisspeptin and neurokinin B across puberty, the menstrual cycle, menopause and reproductive disorders
The review recorded that no licensed pharmacotherapy for low sexual desire existed for men or postmenopausal women, and that the treatments available for premenopausal women, bremelanotide and flibanserin, were limited by their effectiveness or side effects. It also summarised preclinical work indicating that the alpha-melanocyte-stimulating hormone and melanocortin system acts upstream of kisspeptin and depends on kisspeptin signalling to exert its effect on the reproductive phenotype.
- 05Clinical guideline2025
The hormonal regulation of men's sexual desire, arousal, and penile erection: recommendations from the fifth international consultation on sexual medicine (ICSM 2024)
Rastrelli G, et al. · Sexual Medicine Reviews · evidence-graded recommendations from the hormones subcommittee of the fifth International Consultation on Sexual Medicine, covering hypothalamic, pituitary, thyroid, adrenal and sex hormones in men with low desire or erectile dysfunction
The consultation considered kisspeptin and alpha-melanocyte-stimulating hormone among the hypothalamic signals relevant to male sexual function, and reported that both, together with oxytocin, were important in eliciting sexual arousal. It concluded that the use of these peptides or their analogues to stimulate sexual arousal remained under investigation, and reserved its strongest recommendations for testosterone and prolactin assessment.
- 06Animal in vivo2023
Melanocortin 4 receptor signaling in Sim1 neurons permits sexual receptivity in female mice
Semple EA, et al. · Frontiers in Endocrinology · sexual behaviour testing in female melanocortin 4 receptor knockout mice and in mice bred to express the receptor exclusively on Sim1 neurons or on oxytocin neurons
Knockout mice approached males less and showed reduced receptivity to copulation, independently of body weight. Lordosis was normalised in mice expressing the receptor on Sim1 neurons and improved in those expressing it on oxytocin neurons, while approach behaviour was unchanged in the first group and greatly increased in the second. The authors discussed bremelanotide as the approved melanocortin agonist for the disorder and noted that kisspeptin neurons respond to melanocortins, suggesting they may act alongside or downstream of the circuits studied.
- 07Animal in vivo2009
Melanocortins may stimulate reproduction by activating orexin neurons in the dorsomedial hypothalamus and kisspeptin neurons in the preoptic area of the ewe
Backholer K, et al. · Endocrinology · lateral ventricular infusion of the melanocortin agonist melanotan-II, the compound from which bremelanotide derives, in luteal-phase and seasonally anoestrous ewes, with retrograde neuronal tracing and gene expression analysis
Melanocortin agonist infusion during the luteal phase increased luteinising hormone secretion and upregulated kisspeptin expression in the preoptic area and orexin expression in the dorsomedial hypothalamus, while downregulating Kiss1 in the arcuate nucleus. In seasonally anoestrous ewes basal luteinising hormone rose but no ovulatory event was indicated. The authors concluded that melanocortins are positive regulators of the reproductive neuroendocrine system, possibly acting via preoptic kisspeptin cells, but did not overcome seasonal acyclicity.
- 08Review2025
The Concise Guide to PHARMACOLOGY 2025/26: G protein-coupled receptors
Alexander SPH, et al. · British Journal of Pharmacology · expert-curated pharmacological compendium of G protein-coupled receptors, their endogenous ligands and their selective agonists and antagonists
The compendium lists bremelanotide and kisspeptin under separate receptor families, the melanocortin receptors and the kisspeptin receptor respectively, each with its own endogenous ligands and signalling. The two compounds appear in the same reference work only because it catalogues the whole receptor superfamily, and no pharmacological relationship between them is described.
Side by side.
| PT-141 | Kisspeptin-10 | |
|---|---|---|
| Evidence maturity | Approved drug | Early clinical |
| Studies cited here | 15 | 16 |
| Published 2023 or later | 10 | 12 |
| Newest paper | 2026 | 2026 |
| Sequence and origin | A synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone, developed from the melanocortin agonist melanotan-II and first investigated by the intranasal route before redevelopment as a subcutaneous on-demand injection. | A synthetic decapeptide corresponding to the C-terminal fragment of the KISS1 gene product, an endogenous hypothalamic neuropeptide identified through genetic studies of hypogonadotropic hypogonadism. |
| Mechanism as described in the literature | Non-selective agonism at melanocortin receptors, with activity at the melanocortin 4 receptor in central pathways considered central to the effect on sexual response; the mechanism is described as central rather than vascular. | Agonism at the kisspeptin receptor on gonadotropin-releasing hormone neurons and pituitary gonadotrophs, upstream of the reproductive hormone axis, with a separate and more recent line of work on sexual and emotional brain processing. |
| Size of the evidence base | A full development programme. Two identical randomised phase 3 trials enrolled 1,267 premenopausal women, followed by a 52-week open-label extension and an integrated safety analysis across 43 phase 1 to 3 studies in approximately 3,500 subjects. | Small administration experiments. Human work has been predominantly acute, single-centre and conducted largely by one group, and much of the clinical literature used the longer isoform kisspeptin-54 rather than the decapeptide. |
| Best-characterised finding | Statistically significant but small improvements in the desire domain score and reductions in desire-related distress against placebo in the phase 3 programme, with an independent re-analysis reporting effect sizes ranging from nil to small. | A dose-related and sexually dimorphic rise in gonadotropins after administration in healthy volunteers, and in patients with hypoactive sexual desire disorder, modulation of sexual and attraction brain processing on functional neuroimaging. |
| Human data | Randomised placebo-controlled trials with patient-reported efficacy endpoints, an open-label extension and a pooled safety database. No adequately powered indication exists in men or in postmenopausal women. | Randomised crossover neuroimaging trials in men and women with hypoactive sexual desire disorder, plus administration studies in healthy volunteers. No trial has reported a sustained symptomatic endpoint, and the disorder trials used kisspeptin-54. |
| Safety signals reported | Nausea, flushing and headache were each reported by a large minority in the pooled analysis, alongside transient blood pressure elevation; focal hyperpigmentation occurred in more than a third of subjects exposed to consecutive daily dosing, a schedule outside the approved use. | The trials report tolerability without adverse effects, and a 2026 review of peptide availability recorded that no adverse events had yet been published for kisspeptin, which reflects the small size and short duration of the human record rather than an established safety profile. |
| Regulatory status | Approved by the United States regulator in 2019 for generalised acquired hypoactive sexual desire disorder in premenopausal women, and prescribable off-label. Use in men remains investigational. | Investigational everywhere; no kisspeptin peptide is approved as a medicine in any major jurisdiction, and it appears on the United States regulator's category 2 list of bulk drug substances with no or limited safety information. |
| Basis of most marketing claims | Extension of an approved, modest effect in one diagnosis and one population to general libido enhancement in men and women outside that indication, where no adequately powered trial exists. | Extension of acute hormone-release experiments and neuroimaging signals to claims of improved desire and performance, outcomes that no kisspeptin-10 trial has measured as a clinical endpoint. |
And what it does not.
These two peptides have never been compared, and the reason is that they are not alternatives to one another in any published framework. Bremelanotide acts at melanocortin receptors and carries a completed development programme, an approval and a pooled safety database, though independent re-analysis disputes whether its statistically significant effects are clinically meaningful and its tolerability burden is substantial. Kisspeptin acts at a different receptor entirely, sits upstream of the reproductive hormone axis, and its sexual-function work consists of small crossover neuroimaging trials that established a signal rather than a treatment effect, most of them using the longer isoform rather than the decapeptide. The one relationship the literature does describe between them is mechanistic and preclinical: melanocortin agonism activates kisspeptin neurons, and one review reports that the melanocortin effect on the reproductive phenotype depends on kisspeptin signalling. That makes them sequential parts of a circuit in animals, not competing treatments in people. Nothing published supports choosing between them.
Common questions.
- Has any trial compared bremelanotide and kisspeptin directly?
No. Searches of PubMed and Europe PMC returned no study that administered both compounds to the same participants and none that randomised participants between them. The closest published pairing is two separate trials from the same London research group in premenopausal women with hypoactive sexual desire disorder, published in the same month of 2022, each with a placebo comparator. Because the imaging protocols, stimuli and analyses differ between them, their results cannot be placed on a common scale.
- Was the kisspeptin used in the desire trials the same as kisspeptin-10?
No. The randomised crossover trials in hypoactive sexual desire disorder used kisspeptin-54, the longer isoform of the peptide, delivered by intravenous infusion. Kisspeptin-10 is the shorter decapeptide, and a direct comparison in healthy men found that it produced a shorter-lived gonadotropin response than kisspeptin-54. The evidence gaps recorded for kisspeptin-10 include the fact that much of the human clinical work in the field was carried out with the longer form rather than with the decapeptide itself.
- Do the two compounds act on the same receptor system?
They do not. Bremelanotide is a non-selective melanocortin receptor agonist, with melanocortin 4 receptor activity in central pathways considered central to its effect on sexual response. Kisspeptin-10 acts at the kisspeptin receptor, a separate G protein-coupled receptor whose principal described role is regulating gonadotropin-releasing hormone secretion. A pharmacology compendium that lists both places them in different receptor families, and no pharmacological relationship between the two ligands is described in it.
- Is there any published link between the melanocortin and kisspeptin systems?
Yes, at the level of circuitry in animals. Infusion of a melanocortin agonist in ewes increased luteinising hormone secretion and upregulated kisspeptin expression in the preoptic area, and the authors concluded that melanocortins may stimulate reproduction partly through those kisspeptin cells. A physiological review summarises preclinical work indicating that the melanocortin effect on the reproductive phenotype acts upstream of and depends on kisspeptin signalling. These findings describe an interaction between systems, not a comparison between the two marketed peptides.
- How large is the approved effect for bremelanotide?
Modest, and contested. The two identical phase 3 trials in 1,267 premenopausal women reported statistically significant improvements in the desire domain score and reductions in desire-related distress against placebo, with nausea, flushing and headache each reported by at least a tenth of treated participants. An independent re-analysis of the same data reported effect sizes ranging from nil to small, questioned the validity evidence for several outcome instruments, and concluded that most favourable reported outcomes appeared to have been derived post hoc.
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no comparison here should be read as a recommendation of either compound.