R T Chlebowski1, G L Anderson2, G E Sarto2, R Haque2, C D Runowicz2, A K Aragaki2, C A Thomson2, B V Howard2, J Wactawski-Wende2, C Chen2, T E Rohan2, M S Simon2, S D Reed2, J E Manson2. 1. Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM) rowanchlebowski@gmail.com. 2. Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
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 0.625 mg 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.
RCT Entities:
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 0.625 mg 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.
Authors: Vanessa M Barnabei; Barbara B Cochrane; Aaron K Aragaki; Ingrid Nygaard; R Stan Williams; Peter G McGovern; Ronald L Young; Ellen C Wells; Mary Jo O'Sullivan; Bertha Chen; Robert Schenken; Susan R Johnson Journal: Obstet Gynecol Date: 2005-05 Impact factor: 7.661
Authors: James V Lacey; Louise A Brinton; Jay H Lubin; Mark E Sherman; Arthur Schatzkin; Catherine Schairer Journal: Cancer Epidemiol Biomarkers Prev Date: 2005-07 Impact factor: 4.254
Authors: Garnet L Anderson; Howard L Judd; Andrew M Kaunitz; David H Barad; Shirley A A Beresford; Mary Pettinger; James Liu; S Gene McNeeley; Ana Maria Lopez Journal: JAMA Date: 2003-10-01 Impact factor: 56.272
Authors: C M Nagle; L Marquart; C J Bain; S O'Brien; P H Lahmann; M Quinn; M K Oehler; A Obermair; A B Spurdle; P M Webb Journal: Eur J Cancer Date: 2013-04-11 Impact factor: 9.162
Authors: Peter M Ravdin; Kathleen A Cronin; Nadia Howlader; Christine D Berg; Rowan T Chlebowski; Eric J Feuer; Brenda K Edwards; Donald A Berry Journal: N Engl J Med Date: 2007-04-19 Impact factor: 91.245
Authors: Gerardo Heiss; Robert Wallace; Garnet L Anderson; Aaron Aragaki; Shirley A A Beresford; Robert Brzyski; Rowan T Chlebowski; Margery Gass; Andrea LaCroix; JoAnn E Manson; Ross L Prentice; Jacques Rossouw; Marcia L Stefanick Journal: JAMA Date: 2008-03-05 Impact factor: 56.272
Authors: David J Cote; John L Kilgallon; Noah L A Nawabi; Hassan Y Dawood; Timothy R Smith; Ursula B Kaiser; Edward R Laws; JoAnn E Manson; Meir J Stampfer Journal: J Clin Endocrinol Metab Date: 2022-03-24 Impact factor: 5.958
Authors: JoAnn E Manson; Aaron K Aragaki; Jacques E Rossouw; Garnet L Anderson; Ross L Prentice; Andrea Z LaCroix; Rowan T Chlebowski; Barbara V Howard; Cynthia A Thomson; Karen L Margolis; Cora E Lewis; Marcia L Stefanick; Rebecca D Jackson; Karen C Johnson; Lisa W Martin; Sally A Shumaker; Mark A Espeland; Jean Wactawski-Wende Journal: JAMA Date: 2017-09-12 Impact factor: 56.272
Authors: Todd R Sponholtz; Julie R Palmer; Lynn A Rosenberg; Elizabeth E Hatch; Lucile L Adams-Campbell; Lauren A Wise Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-02-23 Impact factor: 4.254
Authors: Elizabeth T Mansi; Kathleen E Malone; Mei-Tzu Tang; Nicole C Loroña; Christopher I Li Journal: Cancer Causes Control Date: 2022-01-21 Impact factor: 2.506
Authors: Madeline E Graham; William G Herbert; Stephanie D Song; Harshini N Raman; Jade E Zhu; Paulina E Gonzalez; Marina R S Walther-António; Marc J Tetel Journal: Trends Endocrinol Metab Date: 2021-05-25 Impact factor: 10.586