The association between testosterone, estradiol, estrogen sulfotransferase and idiopathic pulmonary fibrosis: a bidirectional mendelian randomization study

BackgroundThe causal relationships between testosterone, estradiol, estrogen sulfotransferase, and idiopathic pulmonary fibrosis (IPF) are not well understood. This study employs a bidirectional two-sample Mendelian Randomization (MR) approach to explore these associations.MethodsAll genetic data utilized in our study were obtained from the IEU Open GWAS project. For the MR analysis, we employed the inverse variance weighted (IVW), MR-Egger, and weighted median methods to assess the causal relationships. We also conducted a multivariate MR (MVMR) analysis, with adjustments made for smoking. To ensure the robustness of our findings, sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression, the MR-PRESSO global test, and the leave-one-out method.ResultsGenetically predicted increases in serum testosterone levels by one standard deviation were associated with a 58.7% decrease in the risk of developing IPF (OR = 0.413, PIVW=0.029, 95% CI = 0.187 similar to 0.912), while an increase in serum estrogen sulfotransferase by one standard deviation was associated with a 32.4% increase in risk (OR = 1.324, PIVW=0.006, 95% CI = 1.083 similar to 1.618). No causal relationship was found between estradiol (OR = 1.094, PIVW=0.735, 95% CI = 0.650 similar to 1.841) and the risk of IPF. Reverse MR analysis did not reveal any causal relationship between IPF and testosterone (OR = 1.001, PIVW=0.51, 95% CI = 0.998 similar to 1.004), estradiol (OR = 1.001, PIVW=0.958, 95% CI = 0.982 similar to 1.019), or estrogen sulfotransferase (OR = 0.975, PIVW=0.251, 95% CI = 0.933 similar to 1.018). The MVMR analysis demonstrated that the association between testosterone (OR = 0.442, P = 0.037, 95% CI = 0.205 similar to 0.953) and estrogen sulfotransferase (OR = 1.314, P = 0.001, 95% CI = 1.118 similar to 1.545) and the risk of IPF persisted even after adjusting for smoking.ConclusionsIncreased serum levels of testosterone are associated with a reduced risk of IPF, while increased levels of serum estrogen sulfotransferase are associated with an increased risk. No causal relationship was found between estradiol and the development of IPF. No causal relationship was identified between IPF and testosterone, estradiol, or estrogen sulfotransferase.