Serum Prolactin and Bone Mineral Density in Women with Schizophrenia Receiving Prolactin-Raising Antipsychotics: A Cross-Sectional Study

Background/Objectives: Antipsychotic-induced hyperprolactinemia may adversely affect skeletal health through suppression of the hypothalamic–pituitary–gonadal axis; however, the independent association between circulating prolactin and bone mineral density (BMD) remains uncertain. Methods: This cross-sectional study examined the association between serum prolactin concentration and BMD Z-scores among women with schizophrenia receiving prolactin-raising antipsychotics. Sixty-eight women underwent serum prolactin measurement and dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, and total hip. Because prolactin concentrations were right-skewed, natural-log-transformed prolactin was used in linear regression analyses. Multivariable models adjusted for age, body mass index (BMI), duration of prolactin-raising antipsychotic exposure, chlorpromazine-equivalent dose, and physical activity, with heteroskedasticity-robust standard errors. Results: Median serum prolactin concentration was 44.51 ng/mL (IQR 16.36–78.37). Serum prolactin was not independently associated with BMD Z-score at the lumbar spine (adjusted β = 0.196, 95% CI −0.212 to 0.605; p = 0.340), femoral neck (β = 0.157, 95% CI −0.142 to 0.456; p = 0.298), or total hip (β = −0.224, 95% CI −0.587 to 0.139; p = 0.221). Higher BMI was positively associated with femoral neck and total hip Z-scores, while physical activity was positively associated with BMD Z-scores at all three sites. In a sensitivity analysis restricted to risperidone-treated participants (n = 60), serum prolactin remained unassociated with BMD Z-scores at all sites. Conclusions: In this cohort, contemporaneous serum prolactin concentration was not independently associated with BMD Z-scores. These findings support a multifactorial approach to skeletal health and warrant confirmation in larger longitudinal studies incorporating cumulative prolactin exposure and endocrine and bone-turnover markers.