Introduction:
This study aimed to investigate the causal relationships between air pollution, testosterone levels, and acne using a Mendelian randomization (MR) approach. Air pollution exposure, including nitrogen oxides (Nitrogen oxides air pollution, NOAP), particulate matter (PM2.5 absorbance, nitrogen dioxide (Nitrogen dioxide air pollution, NDAP), PM2.5, and PM10), was analyzed in relation to total testosterone (TTL) and bioavailable testosterone levels (BTL). Given the potential role of environmental and hormonal factors in acne pathogenesis, this study sought to clarify their causal contributions.

Material and methods:
This two-sample Mendelian randomization (MR) study was performed by applying genome-wide association study (GWAS) summary statistics. Multiple MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode, were applied to assess causality. Sensitivity analyses, such as MR-Egger regression, WM, and MR-PRESSO, were conducted to evaluate pleiotropy and heterogeneity.

Results:
Genetically predicted NDAP and PM2.5 exposure exhibited significant causal effects on both TTL and BTL, which in turn were associated with acne development. However, NOAP, PM2.5-10, and PM10 showed no causal links with acne. Sensitivity analyses confirmed the robustness of the IVW results, with no substantial evidence of pleiotropy or heterogeneity.

Conclusions:
This MR study provides evidence supporting a causal role of NDAP and PM2.5 in influencing testosterone levels and acne risk. These findings underscore the importance of environmental factors, particularly air pollution, in modulating hormonal pathways involved in acne. Future research should explore mechanisms underlying these associations,while public health strategies should consider reducing air pollution exposure as part of acne prevention and management approaches.