August 22, 2026 · 2 min read

Bremelanotide (PT-141): a melanocortin agonist and the RECONNECT phase 3 trials

What the two RECONNECT phase 3 trials reported for bremelanotide in premenopausal women with hypoactive sexual desire disorder, and how critics read the results.

Bremelanotide, also known in the research literature as PT-141, is a synthetic peptide that activates melanocortin receptors. It is unusual among the compounds on our list because it has completed phase 3 trials and has been approved in the United States, in 2019, for premenopausal women with hypoactive sexual desire disorder (HSDD). That means there is real controlled trial data to look at, including some skeptical commentary.

The bremelanotide sequence

Sequence: Norleucine, Aspartic acid, Histidine, D-Phenylalanine, Arginine, Tryptophan, Lysine.

  • Modified residue
  • Negatively charged
  • Positively charged
  • Hydrophobic
Length
7 residues, 2 of them modified
Average mass
1,025.2 Da
Formula
C50H68N14O10
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. A ring closes between the Asp and Lys side chains. The mass calculated from this structure matches PubChem (CID 9941379).

The RECONNECT trials

RECONNECT was two identical phase 3, randomized, double-blind, placebo-controlled trials of bremelanotide 1.75 mg given subcutaneously as needed for 24 weeks. In total 1,267 women were randomized. The coprimary endpoints were the change in the FSFI desire domain score and the change in the Female Sexual Distress Scale item on distress about low desire.

Versus placebo, desire scores rose by 0.30 in study 301, 0.42 in study 302 and 0.35 in the integrated analysis, all statistically significant. Distress related to low desire fell by 0.37, 0.29 and 0.33 respectively. Nausea, flushing and headache were more common on bremelanotide, each affecting 10% or more of participants in both studies.

Increase in desire score versus placebo

  • Study 3010.3 points
  • Study 3020.42 points
  • Integrated0.35 points
Difference from placebo in the Female Sexual Function Index desire domain score, end of study (Kingsberg et al., Obstet Gynecol 2019). The scale runs 1.2 to 6.0.

How the results are read

The statistical significance is clear. The size of the effects is a separate debate. A 2024 critical review in the Journal of Sex Research is titled "Small Effects, Questionable Outcomes," and argues that the differences from placebo are modest. That is a fair reading to hold alongside the trial reports, and it is a good example of why effect size matters as much as a p-value.

A long-term safety and efficacy study and a RECONNECT exit study of patient experience complete the picture from the sponsor's program.

Reduction in distress versus placebo

  • Study 301-0.37 points
  • Study 302-0.29 points
  • Integrated-0.33 points
Difference from placebo in the distress item of the Female Sexual Distress Scale, end of study (Kingsberg et al., Obstet Gynecol 2019). Negative means less distress.

References

  1. Kingsberg SA et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol 2019.
  2. Simon JA et al. Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol 2019.
  3. Spielmans GI. Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder. J Sex Res 2024.