Cardiometabolic effects of sequential prolactin states in dopamine agonist-treated prolactinoma patients: a...

Hyperprolactinemia has been associated with adverse cardiometabolic alterations, whereas the metabolic consequences of treatment-induced hypoprolactinemia remain uncertain. We aimed to evaluate longitudinal cardiometabolic changes across sequential prolactin states in dopamine agonist-treated prolactinoma patients.

We conducted a retrospective multicentre longitudinal cohort study including 47 prolactinoma patients from 19 tertiary hospitals in Spain. All patients sequentially transitioned from hyperprolactinemia (HyperPRL) to normoprolactinemia (NormoPRL) and subsequently to hypoprolactinemia (HypoPRL) during cabergoline therapy. Longitudinal changes in anthropometric, hemodynamic, and metabolic parameters were assessed using repeated-measures analyses and generalized estimating equation (GEE) models. Correlation and multivariable regression analyses were performed to evaluate associations between prolactin reduction and metabolic changes.

Transition from HyperPRL to NormoPRL was associated with significant reductions in body weight (80.4 ± 23.6 vs. 78.7 ± 22.8 kg; p = 0.009), body mass index (29.3 ± 7.4 vs. 28.4 ± 7.3 kg/m²; p = 0.034), and total cholesterol (194.3 ± 36.5 vs. 178.7 ± 34.8 mg/dL; p = 0.006). Triglyceride concentrations showed a trend toward reduction across prolactin states, with a significant decrease observed between HyperPRL and NormoPRL. No additional cardiometabolic improvements were detected after transition from NormoPRL to HypoPRL. GEE analyses confirmed significant longitudinal reductions in body weight and total cholesterol after adjustment for age, sex, and initial cabergoline dose, and results remained unchanged in sensitivity analyses additionally accounting for treatment duration. Although percentage prolactin reduction showed a weak inverse association with body weight change in exploratory analyses, no independent associations were identified after multivariable adjustment.

Normalization of prolactin concentrations was associated with significant improvements in body weight, BMI, and total cholesterol concentrations. In contrast, no significant cardiometabolic improvements were detected following the subsequent development of treatment-induced hypoprolactinemia. Furthermore, the magnitude of prolactin reduction was not independently associated with changes in anthropometric or metabolic parameters after multivariable adjustment. These findings suggest that the main cardiometabolic changes occur during the transition from hyperprolactinemia to normoprolactinemia. However, the specific cardiometabolic effects of treatment-induced hypoprolactinemia require confirmation in larger prospective studies.