PT-141 (bremelanotide) and low desire: what the trials and the FDA label show

Most treatments for sexual problems work on blood flow. Sildenafil (Viagra) and tadalafil (Cialis) help the physical response when desire is already present. Bremelanotide, known as PT-141 and sold as Vyleesi, acts somewhere else: on melanocortin receptors in the brain that are involved in sexual motivation. That difference is why the two kinds of drug are studied for different problems and are not interchangeable.

Vyleesi was approved by the FDA in 2019 for acquired, generalised hypoactive sexual desire disorder (HSDD) in premenopausal women. It was the second drug approved for that condition, after flibanserin (Addyi). This page covers what the trials measured, what the label says, and where genetics does and does not fit. The PT-141 reference page has the full evidence summary. Nothing here is medical advice; decisions about any prescription drug belong to you and your prescriber.

How bremelanotide differs from Viagra and Cialis

PDE5 inhibitors such as sildenafil and tadalafil block the enzyme that breaks down cyclic GMP in smooth muscle, which widens blood vessels in the genitals when arousal is already present. They do not act on desire itself.

Bremelanotide activates melanocortin 3 and 4 receptors in the hypothalamus. These receptors are involved in appetite, energy balance and sexual motivation, and activating them is linked to dopamine release in reward areas of the brain. That is the basis for studying it in people whose problem is low desire rather than blood flow.

The early trials in men, and why the nasal spray was dropped

Bremelanotide was first developed by Palatin Technologies as a nasal spray for erectile dysfunction. A phase 2 trial published in Urology in 2004 enrolled 342 men who had not responded to sildenafil; the study reported a treatment success rate of 33.5% on intranasal bremelanotide versus 8.5% on placebo. The nasal formulation was later abandoned after some men in the intranasal trials had significant rises in blood pressure, and development moved to an injection under the skin and to women with HSDD. There is no phase 3 trial of bremelanotide in men, and it is not approved for men.

The broader point about delivery routes is covered in how peptide delivery routes change bioavailability.

What the RECONNECT trials measured

The two phase 3 RECONNECT trials enrolled about 1,200 premenopausal women with HSDD and ran for 24 weeks. Participants used bremelanotide 1.75 mg by subcutaneous injection, as needed, or placebo. Both trials met their co-primary endpoints: an improvement in sexual desire scores and a reduction in the distress associated with low desire, compared with placebo. Source: Vyleesi prescribing information, FDA, 2019.

The approved label for Vyleesi reflects that trial design: 1.75 mg by subcutaneous injection at least 45 minutes before anticipated sexual activity, no more than one dose in 24 hours and no more than eight doses a month. Those are the terms of the approval for premenopausal women with HSDD, and a prescriber decides whether they apply to any individual.

Side effects reported in the trials

The most common side effects in the phase 3 trials were nausea (40%), flushing (20%), injection site reactions (13%) and headache (11%). About 8% of women stopped treatment because of nausea. The label also notes a transient rise in blood pressure after each dose, and lists uncontrolled high blood pressure and known cardiovascular disease as reasons not to use it.

The skin-darkening warning

Bremelanotide activates melanocortin receptors, and the same receptor family regulates skin pigment. The label warns of focal hyperpigmentation:

Hyperpigmentation of the face, gums, and breasts occurred in 1% of women receiving 1.75 mg bremelanotide... These occurred mostly at 5 or more doses and in women with darker skin tones. Some cases did not resolve after discontinuation.

Vyleesi prescribing information, Warnings and Precautions, FDA, 2019 (Section 5.2)

Any change in skin colour is something to raise with the prescriber.

What genetics can and cannot tell you about bremelanotide

Bremelanotide acts on melanocortin receptors, and the gene for the melanocortin 4 receptor (MC4R) carries well-studied variants. Most of that research concerns appetite and body weight: some MC4R variants are linked to higher obesity risk. Further downstream, COMT and DRD2 variants are associated with differences in dopamine signalling.

It is tempting to assume that these variants change how strongly someone responds to bremelanotide. No study has tested that. The RECONNECT trials did not report results by genotype, and no published study has measured bremelanotide response by MC4R, COMT or DRD2 genotype. A DNA report can show which versions of these genes you carry and what the research on them does show; it cannot predict your response to the drug.

A 2025 trial with tirzepatide

Palatin ran a phase 2 trial (BMT-801, ClinicalTrials.gov NCT06565611) giving bremelanotide alongside tirzepatide to people with obesity. The company reported that the study met its primary endpoint, a reduction in the weight regain that usually follows stopping a GLP-1 or GIP drug. The rationale is that MC4R is involved in appetite as well as sexual motivation. It is a phase 2 result reported by the sponsor, and it is not an approved use.

Regulatory status in 2026

Vyleesi, the branded 1.75 mg autoinjector now owned by Cosette Pharmaceuticals, is FDA-approved and available by prescription in the US. Compounded bremelanotide was placed on FDA's restricted list for compounding pharmacies in 2023 to 2024, and the compounding status of several peptides has been under review during 2026. Check the current FDA position rather than relying on any website, this one included. See the 2026 US peptide regulatory guide for the wider framework.