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Dual Outcome Intention-to-treat Analyses in the Women's Health Initiative Randomized Controlled Hormone Therapy Trials.

Published on Apr 21, 2020in American Journal of Epidemiology4.473
· DOI :10.1093/AJE/KWAA033
Ross L. Prentice102
Estimated H-index: 102
(Fred Hutchinson Cancer Research Center),
Aaron K. Aragaki42
Estimated H-index: 42
(Fred Hutchinson Cancer Research Center)
+ 10 AuthorsLihong Qi25
Estimated H-index: 25
(UC Davis: University of California, Davis)
Sources
Abstract
Dual outcome intention-to-treat hazard rate analyses have potential to complement single outcome analyses for the evaluation of treatments or exposures in relation to multivariate time-to-response outcomes. Here we consider pairs formed from important clinical outcomes for further insight into menopausal hormone therapy influences on chronic disease. The Women's Health Initiative randomized, placebo controlled, hormone therapy trials (1993 to present, at 40 U.S. clinical centers) of conjugated equine estrogens (CEE) among post-hysterectomy participants, and of these same estrogens plus medroxyprogesterone acetate (CEE+MPA) among participants with uterus, provides the context for analyses over the trial intervention periods, and over a nearly 20-year (median) cumulative follow-up. The rates of multiple outcome pairs were significantly influenced by hormone therapy, especially over cumulative follow-up, providing potential clinical and mechanistic insights. For example, hazard ratios for pairs defined by fracture during intervention followed by death from any cause were reduced, and by gallbladder disease followed by death were increased, among women randomized to either regimen, though these may primarily reflect single outcome associations. In comparison, hazard ratios for diabetes followed by death were reduced with CEE but not with CEE+MPA, and for hypertension followed by death were increased with CEE+MPA but not with CEE.
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References24
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#1Sybil L. CrawfordH-Index: 54
#2Carolyn J. CrandallH-Index: 33
Last. Hadine JoffeH-Index: 40
view all 7 authors...
AbstractObjective:To better understand how to educate patients and providers about study findings relevant to treatment guidelines, we assessed pre- versus post-Women's Health Initiative (WHI) differences in menopausal hormone therapy (MHT) initiation and continuation and their correlates, and in wo
2 CitationsSource
#1Yael Swica (Columbia University)H-Index: 4
#2Michelle P. WarrenH-Index: 38
Last. Catherine WomackH-Index: 14
view all 10 authors...
OBJECTIVE: The aim of the study was to determine the effect of menopausal hormone therapy on incident hypertension in the two Women's Health Initiative hormone therapy trials and in extended postintervention follow-up. METHODS: A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers. This analysis includes the subsample of 18,015 women who did not report hypertension at baseline and were not taking antihypertensive medication. Women with an intact uterus receive...
4 CitationsSource
#1Joel L. WeissfeldH-Index: 1
#2Wei LiuH-Index: 1
Last. Shelley R. SlaughterH-Index: 2
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OBJECTIVE:We aimed to provide information through 2015 about use in the United States of estrogen products, including orally and vaginally administered products, in postmenopausal women. METHODS:We used prescription claims for US commercial health insurance to calculate, in women 50 years of age or older (n = 12,007,364), the age-standardized and age-specific annual prevalence of estrogen use, by formulation and route of administration, for the period 2006 through 2015. RESULTS:The age-standardi...
3 CitationsSource
#1JoAnn E. Manson (Brigham and Women's Hospital)H-Index: 240
#2Aaron K. Aragaki (Fred Hutchinson Cancer Research Center)H-Index: 42
Last. Jean Wactawski-Wende (UB: University at Buffalo)H-Index: 19
view all 18 authors...
© 2017 American Medical Association. All rights reserved. IMPORTANCE: Health outcomes from the Women’s Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality. OBJECTIVE: To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women’s Health Initiative hormone therapy trials. DESIGN, SE...
108 CitationsSource
#1Joshua A. Roth (Fred Hutchinson Cancer Research Center)H-Index: 11
#2Ruth Etzioni (Fred Hutchinson Cancer Research Center)H-Index: 52
Last. Scott D. Ramsey (Fred Hutchinson Cancer Research Center)H-Index: 61
view all 11 authors...
One of the major debates in public funding of research is its overall return to society. In this context, studies that link National Institutes of Health (NIH)–sponsored research to changes in clinical practice patterns, patient outcomes, and costs are uncommon, although such information could inform debate about the role of publicly funded medical research in the nation’s portfolio of federal health spending. As an example, a decade ago, results of the Women’s Health Initiative (WHI) estrogen p...
23 CitationsSource
#1Shanshan Zhao (Fred Hutchinson Cancer Research Center)H-Index: 15
#2Rowan T. Chlebowski (UCLA: University of California, Los Angeles)H-Index: 80
Last. Ross L. Prentice (Fred Hutchinson Cancer Research Center)H-Index: 102
view all 13 authors...
Introduction: Paradoxically, a breast cancer risk reduction with conjugated equine estrogens (CEE) and a risk elevation with CEE plus medroxyprogesterone acetate (CEE + MPA) were observed in the Women’s Health Initiative (WHI) randomized controlled trials. The effects of hormone therapy on serum sex hormone levels, and on the association between baseline sex hormones and disease risk, may help explain these divergent breast cancer findings. Methods: Serum sex hormone concentrations were measured...
10 CitationsSource
#1JoAnn E. Manson (Harvard University)H-Index: 240
#2Rowan T. Chlebowski (UCLA: University of California, Los Angeles)H-Index: 80
Last. Robert B. Wallace (UI: University of Iowa)H-Index: 11
view all 33 authors...
RESULTS During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits diss...
588 CitationsSource
#1Bruce EttingerH-Index: 60
#2Sharon M. WangH-Index: 3
Last. Michael McBrideH-Index: 1
view all 7 authors...
Objective The results of the Women’s Health Initiative led to a sharp decline in postmenopausal hormone therapy use. Subsequently, treatment guidelines were revised to recommend hormone therapy at the lowest effective dose for the shortest possible duration. The objective of this analysis was to assess trends in nationwide hormone therapy prescription claims from 2002 to 2009. Methods This study was a retrospective database analyses of pharmacy claims from MedImpact Healthcare Systems Inc. Data ...
43 CitationsSource
#1Amy SteinkellnerH-Index: 2
#2Shannon E. DenisonH-Index: 2
Last. Steven J. BowlinH-Index: 4
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AbstractObjectiveNearly a decade ago, landmark clinical trials revealed an increase in the risks associated with hormone therapy in postmenopausal women, leading to early changes in prescribing patterns. Long-term prescribing patterns in the United States after these trials are unknown. The objectiv
60 CitationsSource
#1Garnet L. Anderson (Fred Hutchinson Cancer Research Center)H-Index: 70
#2Rowan T. Chlebowski (Los Angeles Biomedical Research Institute)H-Index: 80
Last. Jean Wactawski-Wende (UB: University at Buffalo)H-Index: 67
view all 15 authors...
Summary Background By contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort. Methods Between 1993 and 1998, the WHI enrolled 10 739 postmenopausal women from 40 US clinical centres ...
235 CitationsSource
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