Risk of schizophrenia in patients with polycystic ovary syndrome: a nationwide population-based cohort study from Taiwan

Abstract

Objectives

To investigate whether patients with polycystic ovary syndrome (PCOS) are at increased risk for incident schizophrenia and whether PCOS treatment (clomiphene, cyproterone, or metformin) affects the incidence of schizophrenia.

Methods

An overall of 7146 PCOS patients and 28,580 non-PCOS controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were included between 2000 and 2012 and followed up until 2013 using a validated nationally representative sample from Taiwan. Participants newly diagnosed as schizophrenia were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of the schizophrenia incidence rate between the two studied groups.

Results

PCOS patients were at increased risk of incident schizophrenia compared to non-PCOS controls after adjusting for age, CCI score, comorbidities, and different treatment options (0.49 versus 0.09 per 1000 person-years, HR: 6.93, 95% CI: 3.25–14.7). After adjusting for above-mentioned covariates, metformin treatment had a protective effect against the incident schizophrenia compared to non-users (HR: 0.16, 95% CI: 0.06–0.41). Also, treatment with clomiphene and cyproterone had only a limited impact on the incident schizophrenia.

Conclusion

This study shows PCOS patients are at increased risk of incident schizophrenia, and the metformin treatment has a protective effect against incident schizophrenia.

Keywords:

• Polycystic ovarian syndrome
• schizophrenia
• clomiphene
• cyproterone
• metformin
• cohort

Acknowledgments

The authors would like to thank Shinn-Zong Lin for cross-hospital integration.

Author contributions

S.F. Chen managed the literature searches and wrote the Introduction of the manuscript. Y.C. Yang and C.Y. Hsu did all the analyses and wrote the Method and Results of the manuscript. Y.C. Shen conceived the study and wrote the Discussion of the manuscript. All authors have approved the final manuscript.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This study is supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW109-TDU-B-212-114004); MOST Clinical Trial Consortium for Stroke, Taiwan (MOST 108-2321-B-039-003); Tseng-Lien Lin Foundation, Taichung, Taiwan. The funding source has no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.