A two-sample bidirectional Mendelian randomization study investigating the causal relationship between polycystic ovary syndrome and testosterone
Objective Polycystic ovary syndrome(PCOS)commonly presents with elevated testosterone levels,manifesting as clinical and/or biochemical hyperandrogenism.Yet,the causal link between PCOS and testosterone(T)remains ambiguous.It's uncertain whether PCOS leads to increased T levels or if elevated T levels contribute to the development of PCOS.This study aims to investigate the causal relationship between PCOS and T levels.Methods Two-sample bidirectional Mendelian randomization(MR)studies were performed based on publicly available statistics from genome-wide association studies.PCOS,total T(TT)and bioavailable T levels were studied.The main analytical method used was inverse variance weighting(IVW).Pleiotropy was evaluated using the MR-Egger intercept.Q and P values were used to assess heterogeneity.Results Genetic determination of PCOS does not lead to an increase in total testosterone(TT)or bioactive testosterone(all P＞0.05).However,elevated TT is associated with an increased risk of PCOS(IVW,OR:1.256,95％CI:1.056-1.495,P=0.010).Additionally,bioactive T also increases the occurrence of PCOS(IVW,OR:1.495,95％CI:1.275-1.752,P=7.440×10-7).The F statistics showed that there was no weak instrumental variable.A sensitivity analysis was performed using the leave-one-out method.No pleiotropy was observed.The results were robust,and the conclusions were reliable.Conclusion This study demonstrates a causal relationship between T(both TT and bioavailable T)and PCOS,indicating that higher levels of T are associated with an increased risk of developing PCOS.These findings strongly support the theory of androgen-induced PCOS,particularly emphasizing the validity of utilizing the androgen-induced PCOS model in research.
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