Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy

WHI Investigators

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)406-414
Number of pages9
JournalAnnals of internal medicine
Volume171
Issue number6
DOIs
StatePublished - Sep 17 2019

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Conjugated (USP) Estrogens
Ovariectomy
Estrogens
Health
Therapeutics
Mortality
Hip Fractures
Women's Health
Hysterectomy
Pulmonary Embolism
Coronary Disease
Colorectal Neoplasms
Ovary
Age Groups
Stroke
Placebos
Breast Neoplasms

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy. / WHI Investigators.

In: Annals of internal medicine, Vol. 171, No. 6, 17.09.2019, p. 406-414.

Research output: Contribution to journalArticle

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title = "Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy",
abstract = "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.",
author = "{WHI Investigators} and Manson, {Jo Ann E.} and Aragaki, {Aaron K.} and Bassuk, {Shari S.} and Chlebowski, {Rowan T.} and Anderson, {Garnet L.} and Rossouw, {Jacques E.} and Howard, {Barbara V.} and Thomson, {Cynthia A.} and Stefanick, {Marcia L.} and Kaunitz, {Andrew M.} and Crandall, {Carolyn J.} and Eaton, {Charles B.} and Henderson, {Victor W.} and Simin Liu and Juhua Luo and Rohan, {Thomas E.} and Shadyab, {Aladdin H.} and Gretchen Wells and Jean Wactawski-Wende and Prentice, {Ross L.}",
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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 E.

AU - Shadyab, Aladdin H.

AU - Wells, Gretchen

AU - Wactawski-Wende, Jean

AU - Prentice, Ross L.

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

VL - 171

SP - 406

EP - 414

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 6

ER -