Identifying Potential Drivers of the Polycystic Ovary Syndrome Burden in the European Union: GBD 2023 SEV Exposure...

The Global Burden of Disease (GBD) study quantifies the burden of polycystic ovary syndrome (PCOS) but does not include PCOS-specific attributable risks. We combined GBD 2023 Summary Exposure Value (SEV) profiling with Mendelian randomization (MR) to identify and prioritize potential drivers of PCOS burden.

We analyzed PCOS incidence, prevalence, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) from 1990 to 2023. Temporal trends were assessed using Estimated Annual Percentage Change (EAPC) and Joinpoint regression. Within the European Union (EU), we evaluated associations between disease burden and Socio-demographic Index (SDI) and cross-checked these findings against Human Development Index (HDI) and Universal Health Coverage (UHC). Expert-screened SEVs were correlated with country-level age-standardized incidence rate (ASIR) using Pearson correlation with Benjamini-Hochberg adjustment; significant exposures were then clustered. Two-sample MR was used to test the effect of nitrogen dioxide (NO₂) on PCOS risk, accompanied by standard sensitivity analyses.

In 2023, the EU ASIR exceeded the global level despite a smaller EAPC, with marked heterogeneity across countries. SDI was positively correlated with PCOS ASRs. SEV screening identified eight exposures associated with ASIR, of which childhood sexual abuse and NO₂ pollution most clearly distinguished high- from low-ASIR countries. MR analysis supported a positive association between genetically predicted NO₂ exposure and PCOS risk (IVW OR 6.60, 95% CI 1.85-23.58; P = 0.00365), with broadly consistent results across sensitivity analyses.

Combining SEV profiling with MR offers a practical approach for prioritizing modifiable drivers of PCOS burden within the GBD framework. NO₂ demonstrated a causal signal, suggesting that air pollution control may represent a viable target for PCOS prevention.