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

Britton Trabert, Sally B. Coburn, Roni T. Falk, Jo Ann E. Manson, Louise A. Brinton, Margery L. Gass, Lewis H. Kuller, Thomas E. Rohan, Ruth M. Pfeiffer, Lihong Qi, Marcia L. Stefanick, Nicolas Wentzensen, Garnet L. Anderson, Xia Xu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1201-1211
Number of pages11
JournalCancer Causes and Control
Volume30
Issue number11
DOIs
StatePublished - Nov 1 2019

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Women's Health
Endometrial Neoplasms
Ovarian Neoplasms
Observational Studies
Estrogens
Hormones
Progestins
Therapeutics
Estradiol
Logistic Models
Odds Ratio
Confidence Intervals

Keywords

  • Current hormone therapy users
  • Endogenous estrogens
  • Endometrial cancer
  • Estrogen metabolites
  • Nested case–control study
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Circulating estrogens and postmenopausal ovarian and endometrial cancer risk among current hormone users in the Women’s Health Initiative Observational Study. / Trabert, Britton; Coburn, Sally B.; Falk, Roni T.; Manson, Jo Ann E.; Brinton, Louise A.; Gass, Margery L.; Kuller, Lewis H.; Rohan, Thomas E.; Pfeiffer, Ruth M.; Qi, Lihong; Stefanick, Marcia L.; Wentzensen, Nicolas; Anderson, Garnet L.; Xu, Xia.

In: Cancer Causes and Control, Vol. 30, No. 11, 01.11.2019, p. 1201-1211.

Research output: Contribution to journalArticle

Trabert, B, Coburn, SB, Falk, RT, Manson, JAE, Brinton, LA, Gass, ML, Kuller, LH, Rohan, TE, Pfeiffer, RM, Qi, L, Stefanick, ML, Wentzensen, N, Anderson, GL & Xu, X 2019, 'Circulating estrogens and postmenopausal ovarian and endometrial cancer risk among current hormone users in the Women’s Health Initiative Observational Study', Cancer Causes and Control, vol. 30, no. 11, pp. 1201-1211. https://doi.org/10.1007/s10552-019-01233-8
Trabert, Britton ; Coburn, Sally B. ; Falk, Roni T. ; Manson, Jo Ann E. ; Brinton, Louise A. ; Gass, Margery L. ; Kuller, Lewis H. ; Rohan, Thomas E. ; Pfeiffer, Ruth M. ; Qi, Lihong ; Stefanick, Marcia L. ; Wentzensen, Nicolas ; Anderson, Garnet L. ; Xu, Xia. / Circulating estrogens and postmenopausal ovarian and endometrial cancer risk among current hormone users in the Women’s Health Initiative Observational Study. In: Cancer Causes and Control. 2019 ; Vol. 30, No. 11. pp. 1201-1211.
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abstract = "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.",
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AU - Falk, Roni T.

AU - Manson, Jo Ann E.

AU - Brinton, Louise A.

AU - Gass, Margery L.

AU - Kuller, Lewis H.

AU - Rohan, Thomas E.

AU - Pfeiffer, Ruth M.

AU - Qi, Lihong

AU - Stefanick, Marcia L.

AU - Wentzensen, Nicolas

AU - Anderson, Garnet L.

AU - Xu, Xia

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N2 - 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.

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