Sex Hormones Increase Endometrial Cancer Risk in Postmenopausal Women: Study

Endometrial cancer, a prevalent gynecologic malignancy, is recognized as hormonally sensitive. Although endogenous sex hormones like estrogens and androgens have long been suspected to play a role in EC risk, results from different studies have been inconsistent. This new meta-analysis sought to combine the evidence regarding the association between several circulating sex hormones such as estrogens, androgens, and SHBG and EC risk, with specific emphasis on postmenopausal women where the hormonal alterations are more significant and the risk for EC is elevated.

The authors performed systematic searches in the PubMed, Web of Science, and Scopus databases to find relevant observational studies. Sixteen included studies were identified as eligible in the final analysis, and they had data that were pooled through a random effects model. The strength of association between hormone level and risk for EC was analyzed using odds ratios (ORs) and 95% confidence intervals (CIs). There was also an analysis of the non-linear dose–response association and the test of the effects of possible modifiers including age, menopausal status, type of cancer, study design, geographic location, and levels of covariate adjustments.

Key Findings

Strong and statistically significant associations between increased levels of certain endogenous hormones and increased EC risk were identified by the meta-analysis:

• Total testosterone: OR 1.70 (95% CI not reported)

• Free testosterone: OR 1.75

• Dehydroepiandrosterone sulfate (DHEAS): OR 1.39

• Androstenedione: OR 1.58

Estrogens also showed strong associations with increased EC risk:

• Estrone: OR 1.55

• Unconjugated estrone: OR 1.86

• Estradiol: OR 1.38

• Unconjugated estradiol: OR 2.14

• Estriol: OR 1.75

• Unconjugated estriol: OR 1.99

• Conjugated estrogens had no marked association with EC risk, implying that the type of estrogen can be very important.

This comprehensive meta-analysis results in the determination that higher endogenous sex hormone levels both androgens and estrogens are predictive of a markedly elevated risk for endometrial cancer in postmenopausal women. Higher levels of SHBG, conversely, would decrease the risk for EC. These results point toward hormone profiling as a worthwhile adjunct to risk assessment for EC and highlight an increased need for monitoring in women postmenopausal with a heightened level of hormones.

Reference:

Zhu, P., Ren, J., Sun, J., Geng, J., Wang, H., & Ma, M. (2025). The association of endogenous sex hormones with endometrial cancer risk: A systematic review and meta-analysis. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 113997, 113997. https://doi.org/10.1016/j.ejogrb.2025.113997