Overall and Sex-Based Risk Factors for Hyperprolactinemia in Patients With Schizophrenia: A Retrospective Cohort Study

Background: Hyperprolactinemia (HPRL) can lead to various health complications. Among patients with schizophrenia, it may be linked to antipsychotic medications and other contributing factors. Sex-based differences in HPRL have been observed, and its association with breast cancer in this population remains unclear. Objective: To investigate overall and sex-specific risk factors for HPRL in patients with schizophrenia and to examine the incidence of breast cancer in this population. Methods: A retrospective cohort study was conducted among inpatients with schizophrenia who underwent prolactin monitoring in a Chinese hospital. Participants were categorized into HPRL and non-HPRL groups, and binary logistic regression was performed to identify factors associated with HPRL. Results: Among 1,425 patients analyzed, the overall incidence of HPRL was 63.37%, with higher rates in females (67.99%) compared to males (57.31%). HPRL was positively associated with thyroid- stimulating hormone levels, repetitive transcranial magnetic stimulation frequency, female sex, and the use of first-generation antipsychotics, amisulpride, olanzapine, risperidone, paliperidone, perospirone, and trihexyphenidyl. Negative associations were found with aspartate aminotransferase, fasting plasma glucose, total bilirubin levels, and aripiprazole use. Sex-specific factors included thyroid- stimulating hormone and sulpiride use in men; olanzapine use in women; and differing associations of aspartate aminotransferase, direct bilirubin, age, and urea nitrogen depending on sex. Four female patients developed breast cancer. Conclusion: Multiple pharmacological and non-pharmacological factors contribute to HPRL in patients with schizophrenia, with notable sex-specific differences. The potential role of HPRL in breast cancer development among female patients requires further investigation.