PT-141
Approved as Vyleesi for low sexual desire in premenopausal women: small average gains in the trials, frequent nausea, and published disputes over how much it helps
PT-141, now bremelanotide, is a seven-amino-acid ring peptide built from the hormone α-MSH that activates melanocortin receptors. As Vyleesi it was approved in June 2019 for acquired, generalized low sexual desire in premenopausal women, injected as needed at least 45 minutes before sex. In two 24-week trials of 1,267 women it raised desire and cut related distress by small margins over placebo, and 40% of women on it had nausea. It did not change the number of satisfying sexual events, and critics argue the gains are too small to matter.
What is it?
Bremelanotide, long known by its development code PT-141, is a seven-amino-acid peptide closed into a ring, built from α-melanocyte-stimulating hormone. It is melanotan II with one change at its tail, a free acid where melanotan II has an amide. Its label says it activates several melanocortin receptors without selectivity, MC1R most potently and then MC4R, and that how it improves low sexual desire is unknown. Work in female rats points to MC4R in the hypothalamus and to dopamine release there.
It was first tested as a nasal spray for erectile dysfunction. In 2004 intranasal doses above 7 mg produced erections within about 30 minutes, and in a 2008 trial of 342 men whose erectile dysfunction had not responded to sildenafil, a 10 mg spray gave a positive clinical result in 33.5% of men against 8.5% on placebo. That form was never approved. The drug that reached the market is a 1.75 mg injection for women.
The approval rests on RECONNECT, two identical 24-week trials in 1,267 premenopausal women with acquired, generalized hypoactive sexual desire disorder. On the two co-primary measures, desire rose 0.30 and 0.42 points more than on placebo, on a score that runs from 1.2 to 6, and distress about low desire fell 0.37 and 0.29 points more. FDA's approval notice put it another way: about 25% of women on the drug gained 1.2 points or more in desire, against about 17% on placebo, and the number of satisfying sexual events did not differ.
Nausea defined the side-effect profile: 40% of women on the drug against 1.3% on placebo, severe enough to need anti-nausea medicine in 13% and to end treatment for 8%. Each dose raises blood pressure by up to 6/3 mmHg for a few hours, and dark patches on the face, gums or breasts appeared in 1% at labelled doses and in 38% of women given daily doses for eight days. Re-analyses of the trial data argue the benefits are modest and rest on poorly validated questionnaires; one found the odds of stopping for side effects about 12 times higher on the drug, and a published commentary disputes that re-analysis.
Mechanism of Action
The label lists bremelanotide's potency at melanocortin receptors in the order MC1R, MC4R, MC3R, MC5R and MC2R, says MC1R and MC4R matter most at the approved dose, and says the mechanism by which it improves desire is unknown. The pathways below combine the label with human and animal studies.
Desire behaviour was shown in rats and the effect in women was measured in two phase 3 trials. Re-analyses argue that effect is small and its measures questionable.
Each step is tagged with where it was shown. A dashed red arrow marks a link the evidence does not establish.
The pathway in words
- Bremelanotide. A synthetic analogue of alpha-MSH, an agonist at melanocortin receptors MC3R and MC4R, injected as needed. Shown in: people. Source: PubMed 16839319.
- Brain desire circuits. In female rats it selectively increased solicitation, a proxy for desire, given under the skin or into the brain's medial preoptic area, not the ventromedial hypothalamus. Shown in: animals. Source: PubMed 17958619.
- Desire in women. In 1,267 premenopausal women with low sexual desire over 24 weeks, desire scores rose 0.35 points and distress fell 0.33 more than on placebo. Shown in: people. Source: PubMed 31599840.
- Approved. Approved in the US in 2019 as Vyleesi for premenopausal women with acquired, generalised hypoactive sexual desire disorder. Shown in: review. Source: PubMed 31429064.
- small, and contested. How much it helps. Re-analyses report small effect sizes, unpublished protocol outcomes and desire measures of questionable validity. Shown in: review. Source: PubMed 33678061, 36809187.
MC4R: desire
Neurons carrying MC4R are spread through the central nervous system. In female rats, bremelanotide injected under the skin or into the medial preoptic area of the hypothalamus selectively increased solicitation, a measure of sexual interest, without changing lordosis, and may work by releasing dopamine there. A 2025 study in female hamsters found it neither changed melanocortin receptors in the brain's reward circuit nor made sex more rewarding.
MC1R: pigment
MC1R drives pigment production in skin, the likely source of the focal hyperpigmentation on the label: 1% of women at up to eight doses a month, and 38% after eight consecutive daily doses. Women with dark skin were more likely to be affected, and FDA's approval notice said the darkening did not go away in about half of affected women after stopping.
Blood pressure and heart rate
In 397 women with normal or controlled blood pressure, ambulatory monitoring found systolic rises of about 3 mmHg over placebo in the four hours after 1.75 mg, with heart rate down by about 4.6 beats a minute; peaks usually lasted under 15 minutes. The label gives maximum rises of 6 mmHg systolic and 3 mmHg diastolic, peaking two to four hours after a dose and usually gone within 12.
Slower stomach emptying
Bremelanotide may slow gastric emptying, which can delay drugs taken by mouth at the same time. Across the development programme it lowered blood levels of indomethacin and naltrexone, and the label says to avoid combining it with oral naltrexone taken for alcohol or opioid dependence, because treatment failure could follow.
Published Research
Our evidence set returned 45 papers on bremelanotide; 28 name it in their titles and 26 of those have an abstract to write from. The 16 cards below are nine human studies, including both phase 3 trials and their year-long extension, five reviews, three of them critical, and two animal studies. One 2008 trial report in women with arousal disorder is left out: its journal retracted it after the author declined to provide the original data. A 2021 commentary rebutting one of the critical re-analyses has no abstract and appears in References without a card.
RECONNECT: the two phase 3 trials
Two identical 24-week trials randomised 1,267 premenopausal women with hypoactive sexual desire disorder to 1.75 mg bremelanotide or placebo, self-injected as needed. Desire scores rose more on the drug (by 0.30 and 0.42 points over placebo; 0.35 combined) and distress about low desire fell more (by 0.37 and 0.29; 0.33 combined), all statistically significant. Nausea, flushing and headache each affected 10% or more of women on the drug in both trials.
The 52-week open-label extension
Of 856 women who finished the core trials, 684 entered a 52-week open-label extension and 272 completed it. Women on bremelanotide from the start ended with desire scores 1.25 to 1.30 points above their original baseline and distress 1.4 to 1.7 points lower; those switched from placebo improved by 0.70 to 0.77 and 0.9. Nausea (40.4%), flushing (20.6%) and headache (12.0%) were the commonest related adverse events. All analyses were descriptive, with no control group.
Phase 2b dose-finding
In a 12-week trial, premenopausal women with sexual dysfunction self-injected placebo or 0.75, 1.25 or 1.75 mg as desired; 327 were in the efficacy analysis. Pooling the two higher doses, satisfying sexual events rose by 0.7 a month against 0.2 on placebo, the sexual function index by 3.6 against 1.9, and the distress score fell by 11.1 against 6.8, all statistically significant. Nausea, flushing and headache were the main adverse events.
Safety across 43 studies
Reviewing 43 completed studies in about 3,500 people, the authors report nausea in 40.0% on bremelanotide against 1.3% on placebo in the pooled phase 3 trials, flushing in 20.3%, headache in 11.3% and injection-site reactions in 5.4%; nausea was the commonest reason to stop, and no one died. Focal hyperpigmentation was rare at label doses but affected more than a third of people given up to 16 consecutive daily doses. After the double-blind phase, 70% on the drug went on to the open-label phase, against 87% on placebo.
Blood pressure, measured around the clock
In 397 premenopausal women with normal or controlled blood pressure, ambulatory monitoring after two doses 24 hours apart found systolic rises over placebo of 3.1 and 3.2 mmHg at 1.75 mg in the four hours after dosing, with similar diastolic rises and heart rate down by 4.6 to 4.7 beats a minute. Peaks typically lasted less than 15 minutes. The results led to in-clinic blood pressure monitoring in the larger trials that followed.
Nasal spray in men
In healthy men and in men with mild-to-moderate erectile dysfunction who responded to Viagra, intranasal PT-141 produced erections significantly more often than placebo at doses above 7 mg, the first appearing about 30 minutes after dosing. Blood levels peaked at a median of 30 minutes, with a mean half-life of 1.85 to 2.09 hours. Flushing and nausea were the commonest adverse events, and no maximum tolerated dose was found.
When sildenafil had failed
Of 342 married men with erectile dysfunction that had not responded to sildenafil, those using a 10 mg bremelanotide nasal spray 45 minutes to 2 hours before sex had a positive clinical result in 33.5% of cases against 8.5% on placebo, and reported more intercourse satisfaction. Drug-related side effects were more common on bremelanotide. The authors call for further studies of doses and regimens.
Arousal disorder: one nasal dose
Eighteen premenopausal women with sexual arousal disorder took a single 20 mg intranasal dose and placebo in a crossover design. More reported moderate or high desire after bremelanotide, and among women who attempted intercourse within 24 hours, more were satisfied with their arousal. Vaginal blood flow measured during erotic videos did not change significantly.
Taken with alcohol
Twenty-four healthy men and women took 20 mg of intranasal bremelanotide, an exposure the authors equate to one to two times the subcutaneous dose, with or without enough alcohol to push women's blood alcohol above 80 mg/dL. The combination was generally well tolerated, with no clinically significant pharmacokinetic interaction, no drug-related drop in blood pressure, and no discontinuations for adverse events.
A critical re-analysis of phase 3
Re-analysing the phase 3 data from FDA's application, the author found results similar to the published ones on the measures reported, but says 72.7% of protocol-listed outcomes went unpublished while 15 unlisted secondary measures were reported. Stopping for adverse events was far more likely on bremelanotide (odds ratio 11.98), and fewer women on the drug both finished the trial and chose to continue (odds ratio 0.30). He concludes the drug is generally not useful.
Small effects, questionable measures
Examining the questionnaires used in RECONNECT, the authors report that the desire and distress scales have questionable validity for women with hypoactive sexual desire disorder, and that 8 of the 11 efficacy outcomes registered on ClinicalTrials.gov had never been published. Analysing those, they found effect sizes from nil to small, and conclude that the benefits are statistically modest and limited to outcomes with scant evidence of validity.
Approved by precedent
A Drug and Therapeutics Bulletin analysis of the trial data behind flibanserin and bremelanotide reports that bremelanotide added no enjoyable sexual experiences, notes shifting primary outcomes and a contested indication, and argues that bremelanotide, with weaker efficacy than flibanserin, benefited from the precedent of flibanserin's approval. The authors call for both approvals to be reconsidered.
Modest benefit, hard trials
A 2023 review describes bremelanotide as moderately safe and well tolerated, with nausea in 40% the commonest adverse reaction, and its overall clinical benefit as modest. It adds that trials in female sexual dysfunction are hard to run well, because placebo effects are large and the outcome measures are open to expectation bias.
First approval
A profile written at approval describes bremelanotide as a self-administered, on-demand subcutaneous melanocortin agonist with high affinity for MC4R. Palatin Technologies developed it and sponsored the phase 3 trials, then licensed North American rights to AMAG Pharmaceuticals, which filed the New Drug Application.
Female rats: more solicitation
In hormone-primed female rats that could pace their encounters with males, bremelanotide sharply and selectively increased solicitations, a proxy for sexual desire, without changing pacing or lordosis. It worked injected under the skin or into the brain's lateral ventricles or medial preoptic area, but not the ventromedial hypothalamus, and may act by activating dopamine terminals in the preoptic area.
Female hamsters: no reward effect
In female Syrian hamsters, most MC3R and MC4R messenger RNA in the ventral tegmental area sat in dopamine neurons. Neither a low nor a high dose of bremelanotide changed melanocortin receptor expression in the reward circuit, and it did not enhance the place preference produced by sexual experience. The authors conclude that it does not act on that circuit or make sex more rewarding.
What people say, and what was measured
PT-141 is bremelanotide, and it is approved, which makes it the opposite case from most of this site: the question is not whether it was tested but how much the tested effect is worth. Its own phase 3 trials have been publicly re-analysed, and that argument belongs beside the claims.
It is clinically proven for low sexual desire — the FDA approved it.
Heard in: Grey Peptides listing review, October 1, 2026: listings cite FDA approval as proof the peptide works. Sellers are not named.
Two phase 3 trials did show a statistically significant improvement in sexual desire and related distress in premenopausal women. Independent re-analyses then argued the effects were modest, that most protocol-listed outcomes went unreported while unlisted ones were published, and that participants discontinued for adverse events far more often on the drug. One re-analysis concludes it is generally not useful; the original authors have replied. PMID: 31599840, 33678061, 36809187, 33835907
Tested in people; mixedIt works through the brain rather than blood flow, so it works where Viagra fails.
Heard in: Grey Peptides listing review, October 1, 2026: listings describe it as a central-acting alternative for people sildenafil does not help. Sellers are not named.
There is a trial of exactly this: 20 men who had failed on sildenafil received bremelanotide in a randomised, double-blind, placebo-controlled study. An earlier study gave intranasal PT-141 to healthy men without any sexual stimulation and recorded a significant erectile response above 7 mg, starting about 30 minutes in, which is what a central mechanism looks like. The approved product is for desire in premenopausal women, not for erectile dysfunction in men. PMID: 18206919, 14963471, 31429064
Tested in people; supportedSide effects are limited to nausea and flushing.
Heard in: Journal of Women's Health, Safety Profile of Bremelanotide Across the Clinical Development Program, the integrated safety analysis the tolerability claims draw on (read October 1, 2026). Source
Nausea, flushing and headache each occurred in 10% or more in both phase 3 trials, so that part is right as far as it goes. The integrated analysis adds that 70% of the bremelanotide group continued into the open-label phase against 87% on placebo, and advises caution in people at cardiovascular risk. Ambulatory monitoring found small transient rises in blood pressure with falls in heart rate, and 26 participants were withdrawn for prespecified blood-pressure increases. PMID: 35147466, 31599840, 27977473
Tested in people; mixedA research vial of PT-141 is the same thing as the approved injection.
Heard in: Grey Peptides listing review, October 1, 2026: listings sell PT-141 vials alongside the approved product's trial results. Sellers are not named.
The trials used a manufactured 1.75 mg subcutaneous autoinjector, dosed as needed under supervision, in a programme whose safety database runs across all its studies. Nothing sold as a research chemical has been through that, and the approval covers one indication in one population. PMID: 31599840, 35147466, 31429064
Never tested in peopleEach claim is quoted from where it is said, never from a seller, and checked as of October 1, 2026 against the studies listed below.
Dosing Data
Bremelanotide has one approved dose: 1.75 mg injected under the skin of the abdomen or thigh with an autoinjector, as needed, at least 45 minutes before expected sexual activity. The label allows one dose in 24 hours, advises against more than eight doses a month, and says to stop after 8 weeks if symptoms have not improved.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
→ Full PT-141 dosage guide — what the Vyleesi label says, the limits it sets, and how online use departs from it.
→ Blend & Stack Calculator — PT-141 is also sold in multi-peptide vials; the calculator shows what each draw delivers of every component; our blends and stacks hub sets out what each mix contains and what has been studied.
Side Effects & Contraindications
Reported Side Effects
From the Vyleesi label's pooled phase 3 data (627 women on the drug, 620 on placebo) unless noted.
Contraindications & Cautions
From the Vyleesi label.
Legal Status
Bremelanotide is an FDA-approved prescription medicine in the United States, sold as Vyleesi. We found no marketing authorisation for it in the other jurisdictions below. Status as of September 26, 2026.
Frequently Asked Questions
?Is PT-141 the same as Vyleesi?
Same molecule, different product. PT-141 was bremelanotide's development code; Vyleesi is the approved 1.75 mg autoinjector. Vials sold online as 'PT-141' for research are not Vyleesi, and the label's doses, limits and safety data were established for the approved product.
?How well does bremelanotide work?
Modestly, on average. In the phase 3 trials desire scores rose 0.35 points more than on placebo, on a scale from 1.2 to 6, and distress fell 0.33 points more. FDA summarised it as about 25% of women gaining at least 1.2 desire points, against about 17% on placebo, with no difference in the number of satisfying sexual events. Critics argue the questionnaires are poorly validated and the gains too small to matter.
?Does PT-141 work for men?
It is not approved for men. Nasal sprays produced erections in early trials, and in 2008 a 10 mg spray gave a positive result in 33.5% of men whose erectile dysfunction had not responded to sildenafil, against 8.5% on placebo, but that form was never approved. The Vyleesi label says it is not indicated for men.
?How common is the nausea, and does it pass?
Nausea affected 40% of women on the drug in the pooled trials, against 1.3% on placebo, most often with the first injection. The label says it got better for most women by the second dose, but 13% needed anti-nausea medicine and 8% stopped treatment because of it.
?Is bremelanotide safe with high blood pressure?
The label contraindicates it in uncontrolled high blood pressure and known cardiovascular disease, and does not recommend it for people at high cardiovascular risk. Each dose raises blood pressure by up to 6/3 mmHg and lowers heart rate by up to 5 beats a minute, peaking two to four hours after injection and usually gone within 12; the one-dose-in-24-hours limit partly guards against additive effects.
?Can it darken the skin?
Yes. Focal hyperpigmentation of the face, gums or breasts was reported in 1% of women taking up to eight doses a month and in 38% of women given daily doses for eight days, more often in women with dark skin. FDA's approval notice said it did not go away in about half of affected women after stopping, and more frequent dosing raises the risk, which is one reason the label advises no more than eight doses a month.
References
- [fda-pi] Vyleesi (bremelanotide injection) Prescribing Information. Cosette Pharmaceuticals, Inc. DailyMed, published November 18, 2025.
- [news-release] U.S. Food and Drug Administration. "FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women." News release, June 21, 2019.
- [clinical-trial] Kingsberg SA, et al. "Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials." Obstet Gynecol, 2019;134(5):899-908. PMID: 31599840.
- [pubmed] Simon JA, et al. "Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder." Obstet Gynecol, 2019;134(5):909-917. PMID: 31599847.
- [clinical-trial] Clayton AH, et al. "Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial." Womens Health (Lond), 2016;12(3):325-37. PMID: 27181790.
- [pubmed] Clayton AH, et al. "Safety Profile of Bremelanotide Across the Clinical Development Program." J Womens Health (Larchmt), 2022;31(2):171-182. PMID: 35147466.
- [pubmed] White WB, et al. "Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide." J Hypertens, 2017;35(4):761-768. PMID: 27977473.
- [pubmed] Diamond LE, et al. "Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction." Int J Impot Res, 2004;16(1):51-9. PMID: 14963471.
- [pubmed] Safarinejad MR, et al. "Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study." J Urol, 2008;179(3):1066-71. PMID: 18206919.
- [pubmed] Diamond LE, et al. "An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist." J Sex Med, 2006;3(4):628-638. PMID: 16839319.
- [pubmed] Clayton AH, et al. "Phase I Randomized Placebo-controlled, Double-blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants." Clin Ther, 2017;39(3):514-526.e14. PMID: 28189361.
- [review] Spielmans GI. "Re-Analyzing Phase III Bremelanotide Trials for "Hypoactive Sexual Desire Disorder" in Women." J Sex Res, 2021;58(9):1085-1105. PMID: 33678061.
- [review] Spielmans GI, et al. "Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder." J Sex Res, 2024;61(4):540-561. PMID: 36809187.
- [review] Mintzes B, et al. "Bremelanotide and flibanserin for low sexual desire in women: the fallacy of regulatory precedent." Drug Ther Bull, 2021;59(12):185-188. PMID: 34642243.
- [review] Cipriani S, et al. "An evaluation of bremelanotide injection for the treatment of hypoactive sexual desire disorder." Expert Opin Pharmacother, 2023;24(1):15-21. PMID: 36242769.
- [review] Dhillon S, et al. "Bremelanotide: First Approval." Drugs, 2019;79(14):1599-1606. PMID: 31429064.
- [pubmed] Pfaus J, et al. "Bremelanotide: an overview of preclinical CNS effects on female sexual function." J Sex Med, 2007;4 Suppl 4:269-79. PMID: 17958619.
- [pubmed] Borland JM, et al. "Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder." Neuropharmacology, 2025;267:110299. PMID: 39793696.
- [pubmed] Kingsberg SA, et al. "Failure of a Meta-analysis: A Commentary on Glen Spielmans's "Re-Analyzing Phase III Bremelanotide Trials for 'Hypoactive Sexual Desire Disorder in Women'"." J Sex Res, 2021;58(9):1106-1107. PMID: 33835907.
Sources & Citations
Every citation on this page is PubMed-indexed and has been checked against its record, except the Vyleesi prescribing information and FDA's 2019 approval notice, which are cited as published. A 2021 commentary appears in References without a card because it has no abstract; the page claims nothing beyond its title. A retracted 2008 trial report is excluded. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.