A critical analysis of the RECONNECT trials found that bremelanotide's benefits for hypoactive sexual desire disorder were statistically modest and relied on outcome measures with questionable validity.
8 of 11 outcomes unpublishedMost pre-specified efficacy outcomes from bremelanotide's pivotal trials were never published — and when analyzed, showed nil to small effect sizes
What the researchers found
8 of 11 clinicaltrials.gov-specified efficacy outcomes were unpublished, including FSDS-DAO total score, FSFI total score, FSFI arousal domain, and FSEP-R items. Analyzed unpublished outcomes showed effect sizes from nil to small. Published categorical response outcomes lacked validity evidence. Nearly all outcomes suggesting modest benefits were likely post-hoc.
Why it matters
Drug approval should be based on meaningful clinical outcomes measured by validated tools. This analysis raises concerns that bremelanotide was approved based on modest improvements in outcomes that may not actually measure what they claim to measure in the target population. This has broader implications for how drugs for sexual health conditions are evaluated.
The numbers in context
Analysis examined the FSFI, FSFI-D (desire domain), and FSDS-DAO questionnaires used in the RECONNECT trials.
How the study worked
Critical review and reanalysis of the Phase III RECONNECT bremelanotide trials. Examined measurement properties and validity evidence for all efficacy outcomes. Obtained and analyzed previously unpublished data from 8 of 11 pre-specified ClinicalTrials.gov outcomes. Evaluated whether published categorical response definitions had supporting validity evidence.
Who was studied
Women with hypoactive sexual desire disorder in RECONNECT trials
What this study cannot tell us
This is a secondary analysis that cannot definitively prove the outcome measures are invalid — it can only demonstrate the absence of supporting validity evidence. The authors did not have access to individual patient data, limiting the depth of their reanalysis. Their critical perspective may underestimate clinically meaningful subjective improvements that are difficult to capture with standardized scales.
How to read the evidence
Moderate evidence for the critique — the reanalysis is thorough and the concerns about selective reporting and outcome validity are well-documented. However, this is a secondary analysis with inherent limitations.
When this study was published
Published in 2024, years after bremelanotide's 2019 FDA approval, providing important post-approval scrutiny of the pivotal trial evidence.
The bigger picture
The approval of drugs for subjective conditions like sexual desire disorders is particularly challenging because outcomes rely on self-reported questionnaires. This critique highlights a broader issue in pharmaceutical research — selective outcome reporting and the use of unvalidated measures can make modest drug effects appear more clinically meaningful than they are.
Questions still open
- Should the FDA reconsider bremelanotide's approval given the concerns about outcome measure validity?
- What validated outcome measures should be used in future trials for female sexual desire disorders?
Common questions
What is bremelanotide?
Does this mean bremelanotide doesn't work at all?
Read the original research
Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder.
Journal of sex research, 61(4), 540-561
Citation
Spielmans, Glen I; Ellefson, Elaine M. (2024). Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder.. Journal of sex research, 61(4), 540-561. https://doi.org/10.1080/00224499.2023.2175192