The U-shaped relationships between prolactin level and insulin resistance in patients with schizophrenia under olanzapine treatment.

Patients with schizophrenia are at elevated risk for metabolic disturbances, particularly when treated with second-generation antipsychotics such as olanzapine. Prolactin elevation is a common adverse effect of antipsychotic therapy, yet its role in glucose homeostasis remains unclear. This study examined the association between serum prolactin levels and insulin resistance in patients with schizophrenia receiving long-term olanzapine treatment. A cross-sectional study was conducted among 310 patients with schizophrenia maintained on olanzapine monotherapy for ≥6 months. Insulin resistance was calculated using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), with a cut-off value of 2.0 indicating insulin resistance. Curve estimation, quartile-based analyses, and multivariate regression models were applied to explore both linear and non-linear associations between prolactin and metabolic indices. The prevalence of metabolic syndrome and hyperprolactinemia was 36.8% and 51.0%, respectively. Prolactin levels were significantly associated with insulin, body mass index (BMI), triglycerides, and HOMA-IR. A quadratic regression model provided the best fit for HOMA-IR, revealing a U-shaped relationship: both low and high prolactin levels were associated with higher insulin resistance. Multivariate analysis confirmed prolactin level and BMI as independent predictors of insulin resistance. Participants were grouped by quartiles of serum prolactin. Compared with Q2, both Q1 and Q4 showed elevated insulin levels and HOMA-IR, indicating nonlinear prolactin-metabolic associations in schizophrenia. This study reveals a U-shaped relationship between prolactin level and insulin resistance in olanzapine-treated schizophrenia. Both hypo- and hyperprolactinemia may be linked to metabolic risk, highlighting the importance of integrated metabolic and endocrine monitoring in psychiatric care.