Estrogen Therapy and Coronary-Artery Calcification
Open accessAbstract
BACKGROUND: Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial. METHODS: In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status. RESULTS: The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence. CONCLUSIONS: Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways. (ClinicalTrials.gov number, NCT00000611.)
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Subsequent analyses of WHI data showed no increase in cardiovascular disease in women starting treatment within 10 years of menopause.
“Subsequent analyses of these data showed no increase in cardiovascular disease in women starting treatment within 10 years of menopause [82].”
From Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014) · cites this paper as [82]
The Abstract reports that secondary WHI analyses found no increased risk of coronary heart disease among women aged 50–59 receiving estrogen, and the Discussion says the findings offer some reassurance about coronary events in women recently past menopause. But the paper does not establish the claim for women specifically starting treatment within 10 years of menopause or for cardiovascular disease broadly; it also reports an increased stroke risk in the estrogen trial. (LLM, conf=0.87)
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- Authors
- Manson, J. E., Allison, M. A., Rossouw, J. E., Carr, J. J., Langer, R. D., Hsia, J., Kuller, L. H., Cochrane, B. B., Hunt, J. R., Ludlam, S. E., Pettinger, M. B., Gass, M., Margolis, K. L., Nathan, L., Ockene, J. K., Prentice, R. L., Robbins, J., & Stefanick, M. L.
- Affiliations
- Brigham and Women's Hospital (US)
- University of California San Diego (US)
- National Institutes of Health (US)
- Wake Forest University Health Sciences (US)
- Geisinger Health System (US)
- George Washington University (US)
- University of Pittsburgh (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- University of Cincinnati (US)
- University of Minnesota (US)
- University of California, Los Angeles (US)
- University of Massachusetts Chan Medical School (US)
- University of California, Davis (US)
- Stanford University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2007-06-21
- Volume
- 356
- Issue
- 25
- Pages
- 2591-2602
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2110885050
- Cited by
- 711
- References
- 38
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 12 · 2023: 17 · 2022: 16 · 2021: 19 · 2020: 24 · 2019: 19 · 2018: 25 · 2017: 27 · 2016: 26 · 2015: 37 · 2014: 35 · 2013: 50 · 2012: 42
- FWCI
- 69.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- Massachusetts Medical Society
- National Heart, Lung, and Blood Institute
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- estrogen therapy, coronary artery calcification, conjugated equine estrogens, Women's Health Initiative, coronary artery calcium score, postmenopausal women, hysterectomy, cardiovascular risk, medication adherence, coronary risk factors, cardiovascular disease prevention, hormone replacement therapy, coronary heart disease prevention
- MeSH terms
- Calcinosis, Coronary Disease, Estrogens, Conjugated (USP), Female, Humans, Hysterectomy, Middle Aged, Risk Factors, Tomography, X-Ray Computed, Estrogen Replacement Therapy, Multivariate Analysis, Logistic Models, Odds Ratio, Coronary Angiography, Postmenopause
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