DataSheet_1_Genetically predicted serum testosterone and risk of gynecological disorders: a Mendelian randomization study.docx

BackgroundTestosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies.MethodsWe leveraged public genome-wide association studies to analyze the effects of four testosterone related exposure factors on nine gynecological diseases. Causal estimates were calculated by inverse variance–weighted (IVW), MR–Egger and weighted median methods. The heterogeneity test was performed on the obtained data through Cochrane’s Q value, and the horizontal pleiotropy test was performed on the data through MR–Egger intercept and MR-PRESSO methods. “mRnd” online analysis tool was used to evaluate the statistical power of MR estimates.ResultsThe results showed that total testosterone and bioavailable testosterone were protective factors for ovarian cancer (odds ratio (OR) = 0.885, P = 0.012; OR = 0.871, P = 0.005) and endometriosis (OR = 0.805, P = 0.020; OR = 0.842, P = 0.028) but were risk factors for endometrial cancer (OR = 1.549, P < 0.001; OR = 1.499, P < 0.001) and polycystic ovary syndrome (PCOS) (OR = 1.606, P = 0.019; OR = 1.637, P = 0.017). dehydroepiandrosterone sulfate (DHEAS) is a protective factor against endometriosis (OR = 0.840, P = 0.016) and premature ovarian failure (POF) (OR = 0.461, P = 0.046) and a risk factor for endometrial cancer (OR= 1.788, P < 0.001) and PCOS (OR= 1.970, P = 0.014). sex hormone-binding globulin (SHBG) is a protective factor against endometrial cancer (OR = 0.823, P < 0.001) and PCOS (OR = 0.715, P = 0.031).ConclusionOur analysis suggested causal associations between serum testosterone level and ovarian cancer, endometrial cancer, endometriosis, PCOS, POF.

背景：睾酮在女性生理中扮演着至关重要的角色，然而，关于血清睾酮水平与妇科疾病风险之间的关联，在观察性研究中尚无定论。方法：本研究利用公开的全基因组关联研究，分析了四种与睾酮相关的暴露因素对九种妇科疾病的影响。通过逆方差加权（IVW）、MR-Egger及加权中位数法计算因果估计值。采用Cochrane的Q值对获得的数据进行异质性检验，并通过MR-Egger截距和MR-PRESSO方法对数据进行水平多效性检验。利用“mRnd”在线分析工具评估了MR估计的统计功效。结果：结果显示，总睾酮和生物可用睾酮是卵巢癌（比值比（OR）= 0.885，P = 0.012；OR = 0.871，P = 0.005）和子宫内膜异位症（OR = 0.805，P = 0.020；OR = 0.842，P = 0.028）的保护因素，但却是子宫内膜癌（OR = 1.549，P < 0.001；OR = 1.499，P < 0.001）和多囊卵巢综合征（PCOS）（OR = 1.606，P = 0.019；OR = 1.637，P = 0.017）的风险因素。脱氢表雄酮硫酸盐（DHEAS）是子宫内膜异位症（OR = 0.840，P = 0.016）和早发性卵巢功能不全（POF）（OR = 0.461，P = 0.046）的保护因素，同时也是子宫内膜癌（OR= 1.788，P < 0.001）和PCOS（OR= 1.970，P = 0.014）的风险因素。性激素结合球蛋白（SHBG）是子宫内膜癌（OR = 0.823，P < 0.001）和PCOS（OR = 0.715，P = 0.031）的保护因素。结论：本研究分析表明，血清睾酮水平与卵巢癌、子宫内膜癌、子宫内膜异位症、PCOS和POF之间存在因果关系。