Circulating estrogens and postmenopausal ovarian and endometrial cancer risk among current hormone users in the Women's Health Initiative Observational Study

Cancer Causes Control. 2019 Nov;30(11):1201-1211. doi: 10.1007/s10552-019-01233-8. Epub 2019 Sep 21.


Purpose: Menopausal hormone therapy (MHT) use induces alterations in circulating estrogens/estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating estrogens/estrogen metabolites and ovarian and endometrial cancer risk among MHT users.

Methods: We conducted a nested case-control study among postmenopausal women using MHT at baseline in the Women's Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype.

Results: Estrogen/estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17-7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to estrogen/estrogen metabolite levels among women who took combined estrogen/progestin therapy (EPT).

Conclusions: These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating estrogens did not influence endometrial cancer risk among women with EPT-induced high-estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and estrogen levels in the context of MHT use.

Keywords: Current hormone therapy users; Endogenous estrogens; Endometrial cancer; Estrogen metabolites; Nested case–control study; Ovarian cancer.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Endometrial Neoplasms / blood*
  • Estradiol / blood*
  • Estrogens / blood*
  • Female
  • Hormone Replacement Therapy*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / blood*
  • Postmenopause
  • Risk


  • Estrogens
  • Estradiol