Effects of glucagon-like peptide-1 analogs on prolactin levels: A secondary analysis of a randomized, double-blind, placebo-controlled crossover trial

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Abstract

Prolactin (PRL) is involved in the modulation of sexual function. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been proposed to modulate reward-related processes beyond their effects on appetite, including sexual desire. In our previously published randomized parent trial of dulaglutide and sexual desire, we hypothesized that any potential effect on sexual desire could involve changes in PRL concentrations. Predefined secondary analysis of a single-center randomized, double blind, placebo-controlled, crossover trial involving 24 healthy eugonad men of normal weight (BMI 18.5-25 kg/m2 or BMI 25.1-30 kg/m2 and waist circumference <102 cm). PRL concentrations were the primary outcome of the present analysis and were measured at baseline and after 4 weeks of dulaglutide (1.5 mg s.c. weekly) and placebo treatment, alongside weight, appetite, and sexual desire. Median age of participants was 24.5 years (IQR [21.0, 29.0]), median BMI was 23.9 kg/m2 (IQR [22.2, 25.0]). PRL levels changed by -31.1 mU/L (SD 87.0 mU/L) on dulaglutide and +44.6 mU/L (SD 113.1 mU/L) on placebo over 4 weeks (estimated difference: -149.3 mU/L; 95% CI: [-298.5, -0.1]). On dulaglutide treatment, reductions in PRL correlated weakly with weight loss (r = 0.25), and more than half of participants (13/24) showed parallel decreases in PRL and appetite scores. Regarding sexuality, we found no association of PRL levels and sexual desire. Four weeks of dulaglutide treatment reduced PRL concentrations compared with placebo in healthy men. These findings may point to broader neuroendocrine effects of GLP-1 receptor activation and warrant further investigation. Trial registration: ClinicalTrials.gov NCT04687514.

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