Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial

R. T. Chlebowski, G. L. Anderson, G. E. Sarto, R. Haque, C. D. Runowicz, A. K. Aragaki, C. A. Thomson, B. V. Howard, J. Wactawski-Wende, C. Chen, Thomas E. Rohan, M. S. Simon, S. D. Reed, J. E. Manson

Research output: Contribution to journalArticle

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Abstract

Background: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. Methods: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. Results: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P =. 007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P =. 008), but hazard ratios did not differ between phases (P difference =. 46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). Conclusion: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

Original languageEnglish (US)
Article numberdjv350
JournalJournal of the National Cancer Institute
Volume108
Issue number3
DOIs
StatePublished - Mar 1 2016

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Women's Health
Progestins
Endometrial Neoplasms
Estrogens
Confidence Intervals
Placebos
Incidence
Conjugated (USP) Estrogens
Medroxyprogesterone Acetate
Uterus
Histology
Randomized Controlled Trials
Hormones
Biopsy
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chlebowski, R. T., Anderson, G. L., Sarto, G. E., Haque, R., Runowicz, C. D., Aragaki, A. K., ... Manson, J. E. (2016). Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial. Journal of the National Cancer Institute, 108(3), [djv350]. https://doi.org/10.1093/jnci/djv350

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer : The Women's Health Initiative Randomized Trial. / Chlebowski, R. T.; Anderson, G. L.; Sarto, G. E.; Haque, R.; Runowicz, C. D.; Aragaki, A. K.; Thomson, C. A.; Howard, B. V.; Wactawski-Wende, J.; Chen, C.; Rohan, Thomas E.; Simon, M. S.; Reed, S. D.; Manson, J. E.

In: Journal of the National Cancer Institute, Vol. 108, No. 3, djv350, 01.03.2016.

Research output: Contribution to journalArticle

Chlebowski, RT, Anderson, GL, Sarto, GE, Haque, R, Runowicz, CD, Aragaki, AK, Thomson, CA, Howard, BV, Wactawski-Wende, J, Chen, C, Rohan, TE, Simon, MS, Reed, SD & Manson, JE 2016, 'Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial', Journal of the National Cancer Institute, vol. 108, no. 3, djv350. https://doi.org/10.1093/jnci/djv350
Chlebowski, R. T. ; Anderson, G. L. ; Sarto, G. E. ; Haque, R. ; Runowicz, C. D. ; Aragaki, A. K. ; Thomson, C. A. ; Howard, B. V. ; Wactawski-Wende, J. ; Chen, C. ; Rohan, Thomas E. ; Simon, M. S. ; Reed, S. D. ; Manson, J. E. / Continuous Combined Estrogen Plus Progestin and Endometrial Cancer : The Women's Health Initiative Randomized Trial. In: Journal of the National Cancer Institute. 2016 ; Vol. 108, No. 3.
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AU - Haque, R.

AU - Runowicz, C. D.

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