TY - JOUR
T1 - Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy
AU - WHI Investigators
AU - Manson, Jo Ann E.
AU - Aragaki, Aaron K.
AU - Bassuk, Shari S.
AU - Chlebowski, Rowan T.
AU - Anderson, Garnet L.
AU - Rossouw, Jacques E.
AU - Howard, Barbara V.
AU - Thomson, Cynthia A.
AU - Stefanick, Marcia L.
AU - Kaunitz, Andrew M.
AU - Crandall, Carolyn J.
AU - Eaton, Charles B.
AU - Henderson, Victor W.
AU - Liu, Simin
AU - Luo, Juhua
AU - Rohan, Thomas
AU - Shadyab, Aladdin H.
AU - Wells, Gretchen
AU - Wactawski-Wende, Jean
AU - Prentice, Ross L.
N1 - Funding Information:
Financial Support: The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268 201600003C, and HHSN268201600004C. Wyeth Ayerst donated the study drugs.
Funding Information:
The WHI is funded by the National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health; and U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs. WHI investigators and representatives of the NHLBI collaborated on the design and conduct of the trial; data interpretation; management, analysis, review, or approval of the manuscript; and the decision to submit the manuscript for publication.
Funding Information:
Primary Funding Source: The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs.
Funding Information:
Disclosures: Dr. Manson reports grants from the National Institutes of Health during the conduct of the study. Dr. Chlebowski reports personal fees from AstraZeneca, Novartis, Genentech, PUMA, Immunomedics, and Amgen during the conduct of the study. Dr. Anderson reports grants from National Heart, Lung, and Blood Institute during the conduct of the study. Dr. Kaunitz reports grants from Bayer, Allergan, Mithra, and Therapeutics MD and personal fees from Bayer, Mithra, and Pfizer outside the submitted work. Dr. Eaton reports grants from National Institutes of Health-WHI during the conduct of the study. Dr. Wactawski-Wende reports grants from the National Institutes of Health during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do ?msNum=M19-0274.
Publisher Copyright:
© 2019 American College of Physicians.
PY - 2019/9/17
Y1 - 2019/9/17
N2 - Background: Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown. Objective: To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups. Design: Subgroup analyses of the randomized Women's Health Initiative Estrogen-Alone Trial. (ClinicalTrials.gov: NCT00000611) Setting: 40 U.S. clinical centers. Participants: 9939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. Intervention: Conjugated equine estrogens (CEE) (0.625 mg/d) or placebo for a median of 7.2 years. Measurements: Incidence of coronary heart disease and invasive breast cancer (the trial's 2 primary end points), all-cause mortality, and a “global index” (these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture) during the intervention phase and 18-year cumulative follow-up. Results: The effects of CEE alone did not differ significantly according to BSO status. However, age modified the effect of CEE in women with prior BSO. During the intervention phase, CEE was significantly associated with a net adverse effect (hazard ratio for global index, 1.42 [95% CI, 1.09 to 1.86]) in older women (aged ≥70 years), but the global index was not elevated in younger women (P trend by age = 0.016). During cumulative follow-up, women aged 50 to 59 years with BSO had a treatment-associated reduction in all-cause mortality (hazard ratio, 0.68 [CI, 0.48 to 0.96]), whereas older women with BSO had no reduction (P trend by age = 0.034). There was no significant association between CEE and outcomes among women with conserved ovaries, regardless of age. Limitations: The timing of CEE in relation to BSO varied; several comparisons were made without adjustment for multiple testing. Conclusion: The effects of CEE did not differ by BSO status in the overall cohort, but some findings varied by age. Among women with prior BSO, in those aged 70 years or older, CEE led to adverse effects during the treatment period, whereas women randomly assigned to CEE before age 60 seemed to derive mortality benefit over the long term.
AB - Background: Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown. Objective: To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups. Design: Subgroup analyses of the randomized Women's Health Initiative Estrogen-Alone Trial. (ClinicalTrials.gov: NCT00000611) Setting: 40 U.S. clinical centers. Participants: 9939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. Intervention: Conjugated equine estrogens (CEE) (0.625 mg/d) or placebo for a median of 7.2 years. Measurements: Incidence of coronary heart disease and invasive breast cancer (the trial's 2 primary end points), all-cause mortality, and a “global index” (these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture) during the intervention phase and 18-year cumulative follow-up. Results: The effects of CEE alone did not differ significantly according to BSO status. However, age modified the effect of CEE in women with prior BSO. During the intervention phase, CEE was significantly associated with a net adverse effect (hazard ratio for global index, 1.42 [95% CI, 1.09 to 1.86]) in older women (aged ≥70 years), but the global index was not elevated in younger women (P trend by age = 0.016). During cumulative follow-up, women aged 50 to 59 years with BSO had a treatment-associated reduction in all-cause mortality (hazard ratio, 0.68 [CI, 0.48 to 0.96]), whereas older women with BSO had no reduction (P trend by age = 0.034). There was no significant association between CEE and outcomes among women with conserved ovaries, regardless of age. Limitations: The timing of CEE in relation to BSO varied; several comparisons were made without adjustment for multiple testing. Conclusion: The effects of CEE did not differ by BSO status in the overall cohort, but some findings varied by age. Among women with prior BSO, in those aged 70 years or older, CEE led to adverse effects during the treatment period, whereas women randomly assigned to CEE before age 60 seemed to derive mortality benefit over the long term.
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U2 - 10.7326/M19-0274
DO - 10.7326/M19-0274
M3 - Article
C2 - 31499528
AN - SCOPUS:85072519391
VL - 171
SP - 406
EP - 414
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
SN - 0003-4819
IS - 6
ER -