PT-141 (Vyleesi) for women: what the RECONNECT trials found

What PT-141 is

PT-141 is the research name for bremelanotide, a synthetic peptide that activates melanocortin receptors in the brain, with high affinity for MC4R. It is derived from α-MSH, the natural hormone that also inspired the tanning peptide melanotan II; its label names MC1R and MC4R as the most relevant receptors at the approved dose and calls the way it improves desire unknown. Palatin Technologies developed it, first testing it as a nasal spray in men with erectile dysfunction before redeveloping it as an injection for women (review and human studies) ^{1 2}. In female rats, it increased behaviours used as a measure of sexual desire without changing other sexual responses (animal evidence) ³.

It is unusual among peptides sold online: the same molecule is an approved drug. FDA approved it on June 21, 2019 as Vyleesi ².

What the label allows

The Vyleesi label indicates it for premenopausal women with acquired, generalised hypoactive sexual desire disorder (HSDD): low sexual desire that causes marked distress or difficulty between partners and is not due to another medical or psychiatric condition, problems in the relationship, or a medication. Its limitations of use are explicit: it is not indicated for HSDD in postmenopausal women or in men, and it is not indicated to enhance sexual performance ⁴.

The labelled dose is 1.75 mg injected under the skin of the abdomen or thigh with an autoinjector, as needed, at least 45 minutes before anticipated sexual activity, with no more than one dose in 24 hours and no more than eight a month recommended. The label adds that how long each dose works is unknown ⁴.

What the RECONNECT trials found

Approval rested on two identical phase 3 trials, RECONNECT studies 301 and 302, run in 2015 and 2016 and funded by the developers. They randomised 1,267 premenopausal women with HSDD, mostly white and from the United States, with an average age of 39, to bremelanotide or placebo, self-injected as needed for 24 weeks. On the two co-primary measures, women on bremelanotide had statistically significant increases in sexual desire (0.30 and 0.42 points over placebo; 0.35 combined) and reductions in distress about low desire (0.37 and 0.29; 0.33 combined) (two randomised trials) ⁵. A pooled analysis found the benefits held across age, weight, body mass and testosterone subgroups, with few exceptions (subgroup analysis) ⁶.

What do those numbers mean? Both scores come from short questionnaire scales, and an average gain of about a third of a point over placebo is modest; critics, below, question how well the scales capture what women experience. In a 52-week open-label extension, women who stayed on bremelanotide reported desire 1.25 to 1.30 points above their original baseline, but only 272 of 684 completed it and there was no control group, so the extension cannot separate the drug from placebo effects and the selection of women who chose to continue (open-label extension) ⁷. An earlier dose-ranging trial reported 0.7 more satisfying sexual events a month on the higher doses against 0.2 on placebo (randomised trial) ⁸.

Why some researchers are unconvinced

Bremelanotide's approval has been criticised in the medical literature. A 2024 analysis of the RECONNECT questionnaires argued that the desire and distress scales have questionable validity for women with HSDD, reported that 8 of the 11 efficacy outcomes registered on ClinicalTrials.gov had not been published, and found effect sizes ranging from nil to small on those outcomes (critical analysis) ⁹. A 2021 re-analysis of FDA's documents reached similar effect sizes on the reported measures, found that women were far more likely to stop for adverse events on the drug, and concluded it is generally not useful (re-analysis) ¹⁰. A Drug and Therapeutics Bulletin analysis reported that bremelanotide added no enjoyable sexual experiences and called for the approval to be reconsidered (independent bulletin) ¹¹.

A 2023 review took a middle position: bremelanotide is moderately safe and well tolerated with a modest overall benefit, in a field where large placebo effects and outcome measures open to expectation make trials hard to run well (review) ¹². All of these analyses agree the effect is small. They differ on whether small is worth having.

How it compares with flibanserin

Bremelanotide was the second drug approved in the US for low desire in premenopausal women. The first, flibanserin, is a daily pill rather than an as-needed injection. The Drug and Therapeutics Bulletin analysis compared the two approvals and argued that bremelanotide, with weaker efficacy than flibanserin, benefited from the regulatory precedent flibanserin had set; it called for both approvals to be reconsidered ¹¹. A 2023 review notes how hard trials in this field are to run well, because placebo effects are large and outcome measures are open to expectation ¹². For a woman choosing between them, the practical differences are the schedule, the route and the side-effect profile, which a prescriber can go through; neither has been compared head to head with the other in a trial we found.

Side effects: nausea, blood pressure and skin darkening

Nausea is the defining side effect. The label reports it in 40% of women using up to eight doses a month; 13% needed anti-nausea medicine and 8% stopped early because of it, though it improved for most with the second dose ⁴. Across the phase 3 trials, nausea occurred in 40.0% on bremelanotide against 1.3% on placebo, flushing in 20.3% and headache in 11.3%, and 70% of the bremelanotide group went on to the open-label phase against 87% on placebo (pooled safety analysis) ¹³.

Each dose briefly raises blood pressure and lowers heart rate. The label reports maximal rises of 6 mmHg systolic and 3 mmHg diastolic, peaking two to four hours after a dose, with heart rate down by up to 5 beats a minute, usually resolving within 12 hours; it advises checking cardiovascular risk first, keeping blood pressure controlled, and says Vyleesi is not recommended for people at high cardiovascular risk ⁴. Ambulatory monitoring in 397 women found similar small rises (randomised trial) ¹⁴.

The third warning is skin darkening. Focal hyperpigmentation, including of the face, gums and breasts, was reported in 1% of women using up to eight doses a month, more often with darker skin and daily dosing, and did not always resolve ⁴; it affected more than a third of people given up to 16 consecutive daily doses in the development programme ¹³. That is a reminder of its melanotan origins, and a reason the label caps use.

Interactions matter too. Vyleesi may slow stomach emptying and reduce absorption of oral medicines that depend on reaching a threshold level, such as antibiotics, and it may significantly lower exposure to oral naltrexone, so it should be avoided with naltrexone products for alcohol or opioid addiction ⁴. A study with alcohol found no clinically significant interaction (human study) ¹⁵.

The menopause gap

Low desire is common after menopause, and PT-141 is often promoted online to postmenopausal women. The RECONNECT trials enrolled only premenopausal women ⁵, and the label states that Vyleesi is not indicated for HSDD in postmenopausal women ⁴. We found no published phase 3 trial of bremelanotide in postmenopausal women in PubMed as of October 3, 2026. Use after menopause is therefore off-label, with no trial showing whether it works or how its blood pressure effects behave in an older population with higher cardiovascular risk.

Prescription Vyleesi versus 'PT-141' vials

Research vials sold as PT-141 contain, at best, the same molecule as Vyleesi, without the autoinjector, the labelled dose or the quality control. Many are promoted for men, for performance or for daily use, all outside the label and, for daily use, linked to the skin darkening seen in the development programme ¹³. For men, a 342-man trial of an earlier nasal version reported some benefit in erectile dysfunction that had not responded to sildenafil, but that form was never approved ².

Questions to ask a doctor about Vyleesi

• Does my situation match the label: premenopausal, acquired and generalised low desire that distresses me, not explained by another condition, my relationship or a medication?
• Is my blood pressure well controlled, and is my cardiovascular risk low enough?
• Do I take naltrexone or oral medicines, such as antibiotics, whose absorption matters?
• How would I manage nausea, and what would make it worth continuing?
• What other approaches, including sex therapy or treating an underlying cause, should come first or alongside?

The bottom line

PT-141 is the rare peptide sold online that is also an approved medicine, but only for a defined group: premenopausal women with acquired, generalised, distressing low desire. In that group the RECONNECT trials found statistically significant but small improvements on questionnaires whose validity is disputed, with nausea in 40% of women and brief rises in blood pressure after each dose. After menopause, in men and for performance, it is off-label and untested in phase 3.

Frequently asked questions

Does PT-141 work for women?

In two trials of 1,267 premenopausal women with low sexual desire, bremelanotide improved desire by about 0.35 points and reduced distress by about 0.33 points over placebo on questionnaires. The effects were statistically significant but small.

What are the side effects of Vyleesi?

Nausea in 40% of women, flushing, headache, brief rises in blood pressure after each dose, and focal skin darkening in about 1% using it up to eight times a month.

Can postmenopausal women use PT-141?

The Vyleesi label says it is not indicated for postmenopausal women, and the phase 3 trials enrolled only premenopausal women.

Is PT-141 the same as Vyleesi?

PT-141 is bremelanotide, the active ingredient in Vyleesi. Research vials sold as PT-141 are not the approved product and lack its dosing, device and quality control.

How often can Vyleesi be used?

The label says no more than one dose in 24 hours and no more than eight doses a month are recommended.

Related on Grey Peptides

• PT-141 (bremelanotide)
• Melanotan II
• Kisspeptin and fertility

Sources

1. Dhillon, S., et al. (2019). Bremelanotide: First Approval. Drugs, 79(14), 1599-1606. PMID: 31429064
2. Grey Peptides encyclopedia entry for PT-141 (bremelanotide): FDA approval June 21, 2019 as Vyleesi, development history, WADA status (not listed), study cards including the 2008 nasal-spray trial in men. Read October 3, 2026.
3. Pfaus, J., et al. (2007). Bremelanotide: an overview of preclinical CNS effects on female sexual function. J Sex Med, 4 Suppl 4, 269-79. PMID: 17958619
4. VYLEESI (bremelanotide injection) US prescribing information: Indications and Usage with Limitations of Use, Dosage and Administration, Warnings and Precautions 5.1-5.3, Drug Interactions 7.1-7.2. DailyMed version 1, effective November 13, 2025; read October 1, 2026.
5. Kingsberg, S. A., et al. (2019). Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol, 134(5), 899-908. PMID: 31599840
6. Simon, J. A., et al. (2022). Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide. J Womens Health (Larchmt), 31(3), 391-400. PMID: 35230162
7. Simon, J. A., et al. (2019). Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol, 134(5), 909-917. PMID: 31599847
8. Clayton, A. H., et al. (2016). Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Womens Health (Lond), 12(3), 325-37. PMID: 27181790
9. Spielmans, G. I., et al. (2024). Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder. J Sex Res, 61(4), 540-561. PMID: 36809187
10. Spielmans, G. I. (2021). Re-Analyzing Phase III Bremelanotide Trials for "Hypoactive Sexual Desire Disorder" in Women. J Sex Res, 58(9), 1085-1105. PMID: 33678061
11. Mintzes, B., et al. (2021). Bremelanotide and flibanserin for low sexual desire in women: the fallacy of regulatory precedent. Drug Ther Bull, 59(12), 185-188. PMID: 34642243
12. Cipriani, S., et al. (2023). An evaluation of bremelanotide injection for the treatment of hypoactive sexual desire disorder. Expert Opin Pharmacother, 24(1), 15-21. PMID: 36242769
13. Clayton, A. H., et al. (2022). Safety Profile of Bremelanotide Across the Clinical Development Program. J Womens Health (Larchmt), 31(2), 171-182. PMID: 35147466
14. White, W. B., et al. (2017). Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide. J Hypertens, 35(4), 761-768. PMID: 27977473
15. Clayton, A. H., et al. (2017). 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, 39(3), 514-526.e14. PMID: 28189361

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. 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.