TY - JOUR
T1 - Continuous Combined Estrogen Plus Progestin and Endometrial Cancer
T2 - The Women's Health Initiative Randomized Trial
AU - Chlebowski, R. T.
AU - Anderson, G. L.
AU - Sarto, G. E.
AU - Haque, R.
AU - Runowicz, C. D.
AU - Aragaki, A. K.
AU - Thomson, C. A.
AU - Howard, B. V.
AU - Wactawski-Wende, J.
AU - Chen, C.
AU - Rohan, T. E.
AU - Simon, M. S.
AU - Reed, S. D.
AU - Manson, J. E.
N1 - Publisher Copyright:
© 2015 The Author 2015. Published by Oxford University Press. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84959009500&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959009500&partnerID=8YFLogxK
U2 - 10.1093/jnci/djv350
DO - 10.1093/jnci/djv350
M3 - Article
C2 - 26668177
AN - SCOPUS:84959009500
SN - 0027-8874
VL - 108
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 3
M1 - djv350
ER -
