Schizophrenia may be a risk of polycystic ovary syndrome (PCOS) and primary ovarian insufficiency (POI): A Mendelian randomisation study

Polycystic ovary syndrome (PCOS) and primary ovarian insufficiency (POI) are significant causes of female infertility. Women with schizophrenia exhibit reduced fertility, and existing research indicates associations between schizophrenia and PCOS, though causality remains uncertain. Furthermore, the relationship between schizophrenia and POI has not been elucidated. The study utilised Genome-wide association study (GWAS) data from Psychiatric Genomics Consortium (PGC) database and European populations (schizophrenia: <i>n</i> = 127,906; PCOS: 642 cases, 118,228 controls; POI: 254 cases, 1,182,288 controls). Single-nucleotide polymorphisms (SNPs) of genome-wide significance were selected as instrumental variables (IVs). Various sensitivity analyses were employed to validate the causality between schizophrenia and PCOS/POI. Schizophrenia increased the risk of PCOS (OR= 1.070, 95% CI: 1.024 to 1.119, <i>p</i> = 0.002), and had a potential causal relationship with POI (OR= 1.316, 95% CI: 1.011 to 1.713, <i>p</i> = 0.041). These results were robust in sensitivity analysis, with no heterogeneity or pleiotropy detected. These results reveal the potential mechanisms underlying reduced fertility in schizophrenia and provide a novel perspective on the link between psychiatry and reproductive endocrinology, motivating further investigation. Meanwhile, this study underscores the clinical imperative for enhanced surveillance of ovarian function and timely fertility assessment in patients to optimise outcomes.