Sex differences in cardiovascular risk factors and cardiovascular disease in patients with hyperprolactinemia: a multicenter cross-sectional study

Abstract

[Abstract] Introduction. Hyperprolactinemia is classically linked to reproductive dysfunction, but emerging evidence suggests an association with metabolic and cardiovascular (CV) risk. This study evaluated sex differences in CV risk factors (CVRFs) and cardiovascular disease (CVD) in patients with hyperprolactinemia.

Methods. A multicenter, retrospective cross-sectional study was conducted in 449 adult patients (199 men, 250 women) with confirmed hyperprolactinemia from 19 tertiary referral centers in Spain. Clinical, biochemical, and hormonal data were collected and analyzed. The prevalence of CVRFs and CVD was compared between sexes. Associations between serum prolactin levels and CVRFs/CVD were assessed using nonparametric tests, correlation analyses, and multivariable logistic regression.

Results. Men had significantly higher serum prolactin levels than women (median 796 [IQR 250–1499] vs. 114 [74.5–224] ng/mL; p < 0.001) and a greater crude prevalence of all major CVRFs (p < 0.001 for all). After adjustment for age, male sex remained independently associated with smoking (OR 2.16; p = 0.007) and hyperlipidemia (OR 1.97; p = 0.031). Serum prolactin levels positively correlated with age, BMI, systolic blood pressure, glucose, total cholesterol, and triglycerides (all p < 0.001). In sex-stratified analyses, prolactin was associated with BMI and lipid profile in men, and with hypertension and hyperlipidemia in women. Prolactin levels were significantly elevated in patients with any form of CVD (p = 0.007), particularly arrhythmias (p = 0.013), while a trend was noted for ischemic heart disease (p = 0.050).

Conclusion. Men with hyperprolactinemia exhibit a more adverse cardiometabolic profile, characterized by higher serum prolactin levels and a greater burden of classical CVRFs and CVD. Prolactin concentrations are positively associated with multiple metabolic and CV parameters, with sex-specific patterns suggesting distinct mechanisms of susceptibility and regulation. These findings underscore the importance of incorporating sex and hormonal context into CV risk assessment in patients with hyperprolactinemia.