Reproductive Outcome Registration in Phase 3 Weight-Management Pharmacotherapy Trials: A Cross-Sectional Meta-Research Study.

Abstract

To quantify registered reproductive outcome measures in women and men in adult Phase 3 weight-management pharmacotherapy trials and compare them with registered body-composition measures. Cross-sectional meta-research study of ClinicalTrials.gov records as registered on 31 August 2026. Eligible trials were randomised, controlled, Phase 3 or 2/3, with registered minimum age ≥ 18 years, a pharmacological intervention, weight or BMI as a registered primary outcome and a weight-related registered condition. Registered outcome fields were classified with a published dictionary. Analyses used exact Clopper-Pearson intervals and paired counts; programme-level, mechanism and age-relaxed analyses were post hoc. Of 230 trials (91 development programmes; 3711 registered outcome measures), two registered any reproductive outcome measure (0.87%, 95% CI: 0.11-3.11), both in polycystic ovary syndrome populations with non-industry sponsors; none of 227 trials without a reproductive indication did. No trial enrolling men registered a named male gonadal-endocrine or semen measure (0/228, 95% CI: 0.00-1.60). Among trials of glucagon-like peptide-1-based agents it was 2/152 (1.32%). Body composition was registered in 33 trials, 31 without any reproductive measure and none the reverse; at programme level, 22 versus none. Admitting trials with minimum age below 18 years gave 7/254 (2.76%), including two industry trials registering gonadal hormones in adolescent safety panels. Qualifying reproductive outcomes were rarely registered in adult Phase 3 weight-management pharmacotherapy trials on ClinicalTrials.gov, including 31 of 33 trials registering body composition. This identifies a gap in publicly registered evidence, not absence of measurement; registering reproductive assessments where undertaken would improve their discoverability.