Main MR analysis
For the main MR analysis, we used the inverse-variance weighted (IVW)
method 23. This method assumes that all instruments
are valid, although it can still provide unbiased estimates in some
scenarios where the IV assumptions are violated (e.g., balanced
horizontal pleiotropy). In this study, our focus is on effect size and
precision, and we interpret p-values as indicators of the strength of
evidence 24,25. Since we examined four sex hormones
(estradiol, TT, BT and SHBG) in the MR analysis, we considered a p-value
less than 0.0125 (0.05/4) as strong evidence for MR estimates, and a
p-value between 0.0125 and 0.05 as suggestive causal evidence.