The association of endogenous sex hormones with endometrial cancer risk: A systematic review and meta-analysis
The role of endogenous sex hormones in the risk of endometrial cancer (EC) remains contradictory across the studies. This meta-analysis was carried out to investigate the relation of circulating concentrations of sex hormones and sex hormone-binding globulin (SHBG) to EC risk. A search of the PubMed, Web of Science, and Scopus databases was conducted to include relevant studies. We used odds ratios (OR) with 95% confidence intervals (CI) to pool effect sizes using a random effects model. The analysis included 16 studies with 292,695 participants. SHBG levels showed an inverse relationship with EC (OR: 0.67). In contrast, higher circulating levels of total testosterone (OR: 1.70), free testosterone (OR: 1.75), dehydroepiandrosterone sulfate (OR: 1.39), and androstenedione (OR: 1.58) were positively associated with EC risk. Estrogens also demonstrated significant associations, so that estrone (OR: 1.55), unconjugated estrone (OR: 1.86), estradiol (OR: 1.38), unconjugated estradiol (OR: 2.14), estriol (OR: 1.75), and unconjugated estriol (OR: 1.99) were linked to increased EC risk, while conjugated estrogens showed no significant associations. A non-linear dose-response relationship was found for SHBG, estrone, estradiol, and total testosterone. The results were significantly affected by age, cancer type, geographic region, menopausal status, study type, and the level of adjustments for covariates. For all hormones, the significant associations were found only for postmenopausal women. This study found an inverse association between SHBG and EC, while identified a direct relationship between sex hormones, except for conjugated estrogens, and EC risk only in postmenopausal women.