An approved drug with a narrow label, a modest effect size, a blood pressure warning, and a gray-market afterlife in the one population its label says it is not for.

Summary

  • PT-141 is bremelanotide, a cyclic seven-residue melanocortin receptor agonist derived from melanotan II, itself derived from the pigment hormone alpha-MSH. It acts on melanocortin-4 receptors in the brain rather than on blood flow.1

  • Approved by the FDA on 21 June 2019 as Vyleesi, for premenopausal women with acquired, generalised hypoactive sexual desire disorder. The label states it "is not indicated for the treatment of HSDD in postmenopausal women or in men" and "is not indicated to enhance sexual performance."2

  • In two identical Phase 3 trials of 1,267 women, 24 weeks of as-needed 1.75 mg increased a desire score by 0.35 points against placebo on a scale that runs from 1.2 to 6, and reduced a distress score by 0.33 points. Both differences were statistically significant.3

  • Nausea affected 40 percent of women, needed anti-emetics in 13 percent and caused 8 percent to stop. Each dose transiently raises blood pressure and lowers heart rate, and the drug is contraindicated in uncontrolled hypertension or known cardiovascular disease.2

  • Focal hyperpigmentation of the face, gums or breasts occurred in 1 percent at labelled doses, more with darker skin and daily use, and did not always resolve.2

  • In men, intranasal PT-141 produced erections in early trials and helped a third of sildenafil non-responders in a 2008 trial. That programme was not carried to approval, and no bremelanotide product is approved for men anywhere.45

  • The gray market sells "PT-141" almost entirely to men, as powder for injection, often from the same suppliers as melanotan II, which the FDA lists for melanoma, priapism and posterior reversible encephalopathy syndrome.6

  • Not named on the WADA Prohibited List.

The Most Common Error About This Compound

Reading "FDA-approved" as approval of the use being sold. Bremelanotide is approved for one condition in one population, on the basis of an effect its own reviewers described as modest, with a cardiovascular warning attached.3 The label excludes men and excludes performance enhancement in so many words.2 A vial of PT-141 sold to a man for that purpose is borrowing an approval that was written to exclude him.

Identity

What Is PT-141?

Alpha-melanocyte-stimulating hormone acts on melanocortin receptors to darken skin, suppress appetite and, through MC4 receptors in the hypothalamus, modulate sexual arousal. Melanotan II is a cyclic synthetic analogue developed as a tanning agent in the 1990s; its unexpected side effect in early trials was spontaneous erections. Bremelanotide, PT-141, is melanotan II with its C-terminal amide replaced by a carboxyl group, a metabolite that keeps the sexual effect and loses most of the tanning.1 Palatin Technologies developed it, first as a nasal spray for men and then as an injection for women, and AMAG Pharmaceuticals marketed it at launch. Since 2023 Vyleesi has been held by Cosette Pharmaceuticals.2

How Does It Work?

Centrally. Unlike sildenafil and its relatives, which act on blood vessels, bremelanotide acts on MC4 receptors in the brain to shift the balance of dopaminergic excitation and serotonergic inhibition that governs desire.1 That is why it was tested for desire in women, why it produced erections in men without sexual stimulation in the first studies, and why its side effects, nausea, flushing and blood pressure changes, are systemic rather than local.4

Evidence Base

What Did the Approval Trials Show?

RECONNECT was two identical 24-week randomised, double-blind, placebo-controlled trials in premenopausal women with acquired, generalised HSDD, using 1.75 mg subcutaneously as needed. Of 1,267 randomised, 1,247 were in the safety population, 96.6 percent at US sites, mean age 39, 85.6 percent white.

The co-primary endpoints were the desire domain of the Female Sexual Function Index and a single distress item. Desire scores rose by 0.30 and 0.42 points more than placebo in the two studies, 0.35 integrated; distress fell by 0.37 and 0.29 more, 0.33 integrated. All were statistically significant. Nausea, flushing and headache each affected 10 percent or more.3

The desire domain runs from 1.2 to 6. A 0.35-point advantage over placebo is real, reproduced, and small; the question of whether it is clinically meaningful was debated at approval and remains a matter of judgement rather than data. Subgroup analyses found the effect broadly consistent across age, weight and prior treatment.7

What Happened With Men?

The compound started as a men's drug. In 2004 intranasal PT-141 produced statistically significant erectile responses in healthy men without visual stimulation and in sildenafil-responsive men with it, at doses above 7 mg, with onset around 30 minutes and no maximum tolerated dose identified.4 A 2008 trial in 342 sildenafil non-responders found positive responses in 33.5 percent on 10 mg intranasal bremelanotide against 8.5 percent on placebo, with more drug-related adverse effects.5

The intranasal programme was not taken to approval; Palatin redirected the compound to subcutaneous use in women. The blood pressure effect that the women's label now warns about was a consideration throughout. The result is that the population with the most dramatic early signal has no approved product, and the product that exists is labelled to exclude them.2

Is There Evidence for Off-Label Use?

For men with erectile dysfunction, the early trials above, by a route that is not sold and at doses that do not correspond to the approved injection. For men or women seeking "libido enhancement" without a diagnosis, for postmenopausal women, or for anyone using it daily, nothing. The label's limitation of use, "not indicated to enhance sexual performance," describes the gap.2

Safety

What Does the Label Say?

Three warnings carry the weight. Each dose produces a transient rise in blood pressure and fall in heart rate that usually resolves within 12 hours; the drug is contraindicated in uncontrolled hypertension or known cardiovascular disease, not recommended in anyone at high cardiovascular risk, and limited to one dose per 24 hours and eight per month partly to avoid additive blood pressure effects. Focal hyperpigmentation of the face, gingiva and breasts occurred in 1 percent at labelled doses, with higher risk in darker skin and with daily dosing, and did not always resolve. Nausea affected 40 percent, improving for most after the second dose.2

It slows gastric emptying, which can reduce absorption of oral drugs, and it can substantially reduce exposure to oral naltrexone, so the label says to avoid it in people taking naltrexone for alcohol or opioid dependence.2

Why the Dose Ceiling Matters for the Gray Market

The eight-doses-a-month limit is not arbitrary. The hyperpigmentation rate rose with daily dosing, and the blood pressure effect is additive. Community protocols for men use PT-141 more often and at higher doses than the label, without the cardiovascular screening the label requires and without a blood pressure cuff. The one safety property the approval established, that the drug is acceptable at eight doses a month in women with screened hearts, is the property the gray market discards first.2

What Is Unknown

Long-term safety beyond 24 weeks of as-needed use. Safety in men at any dose by injection, since the men's trials were intranasal. Whether the pigmentation effect, which comes from the same receptor family that drives melanoma risk with melanotan II, has consequences over years of use. The label reports what the trials measured; it does not answer questions the trials did not ask.

Regulatory Status

Where Is It Approved?

In the United States, since 21 June 2019, for premenopausal HSDD. It has not been approved by the European Medicines Agency, and ONPEPS is not aware of an approval elsewhere.

Can It Be Compounded?

Bremelanotide is the active ingredient of an approved drug, which makes it eligible for 503A compounding without a bulks-list entry, subject to the rule against producing what is "essentially a copy" of a commercially available product. The FDA's guidance treats a compounded product with the same active ingredient, a similar strength and the same route as a copy unless a prescriber documents a patient-specific difference, and it states that a lower price is not one.8 A compounded 1.75 mg subcutaneous bremelanotide for a woman who could use Vyleesi is a copy. A compounded product for a man is not a copy of anything approved, because nothing is approved for him; it is off-label prescribing of a compounded version of a drug labelled to exclude him. The sourcing page covers what that means for the product actually sold.

Related ONPEPS Coverage

What Would Change This Page

A controlled trial of subcutaneous bremelanotide in men, which would be the first and which no sponsor has registered. Long-term safety data on pigmentation and blood pressure beyond 24 weeks. A European decision, if the holder ever files.

References

  1. Pfaus JG, Sadiq A, Spana C, Clayton AH. The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women. CNS Spectr. 2022;27(3):281-289. Open access; authors include company employees. pubmed.ncbi.nlm.nih.gov/33455598

  2. Cosette Pharmaceuticals, Inc. VYLEESI (bremelanotide) injection: prescribing information. Revised March 2024. DailyMed. dailymed.nlm.nih.gov

  3. Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol. 2019;134(5):899-908. Open access. pubmed.ncbi.nlm.nih.gov/31599840

  4. Diamond LE, Earle DC, Rosen RC, Willett MS, Molinoff PB. 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):51-59. Paywalled. pubmed.ncbi.nlm.nih.gov/14963471

  5. Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study. J Urol. 2008;179(3):1066-1071. Paywalled. pubmed.ncbi.nlm.nih.gov/18206919

  6. US Food and Drug Administration. Category 2 of the Bulk Substances Nominated Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act. Entry for Melanotan II. Content current as of 22 April 2026. fda.gov

  7. Simon JA, Kingsberg SA, Portman D, Jordan R, Lucas J, Sadiq A, et al. Prespecified and integrated subgroup analyses from the RECONNECT phase 3 studies of bremelanotide. J Womens Health (Larchmt). 2022;31(3):391-400. Open access. pubmed.ncbi.nlm.nih.gov/35230162

  8. US Food and Drug Administration. Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act: Guidance for Industry. January 2018. fda.gov

Not Medical Advice

Bremelanotide is an approved prescription medicine for one indication in one population, with cardiovascular contraindications and dose limits set out in its label. Nothing here substitutes for that label or for a prescriber who has read it. Consult a qualified healthcare provider before acting on anything here.

Evidence counts on the library index retrieved 23 July 2026. Literature, label and regulatory sources verified 16 September 2026. Re-verify before relying on any regulatory statement here.