The DOI matches its Crossref record, with a small difference in title or year; 34 of the 35 references it cites were found in a registry or an index.
Estrogen plus Progestin and the Risk of Coronary Heart Disease
Open accessAbstract
BACKGROUND: Recent randomized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease (CHD). In this report, we provide the final results with regard to estrogen plus progestin and CHD from the Women's Health Initiative (WHI). METHODS: The WHI included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line. Participants were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The primary efficacy outcome of the trial was CHD (nonfatal myocardial infarction or death due to CHD). RESULTS: After a mean follow-up of 5.2 years (planned duration, 8.5 years), the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits. Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95 percent confidence interval after adjustment for sequential monitoring, 0.97 to 1.60). The elevation in risk was most apparent at one year (hazard ratio, 1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy, higher base-line levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD. CONCLUSIONS: Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.
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In the citing paper
“Although there have been no placebo-controlled trials in children, observational studies have suggested that early treatment can reduce LDL-C burden, improve endothelial function, substantially attenuate the development of atherosclerosis, and improve coronary outcomes [369-371].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [371]
Experimental — accuracy not yet measuredIn the citing paper
“Although there have been no placebo-controlled trials in children, observational studies have suggested that early treatment can reduce LDL-C burden, improve endothelial function, substantially attenuate the development of atherosclerosis, and improve coronary outcomes [369-371].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [371]
In the citing paper
“Although there have been no placebo-controlled trials in children, observational studies have suggested that early treatment can reduce LDL-C burden, improve endothelial function, substantially attenuate the development of atherosclerosis, and improve coronary outcomes [369-371].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [371]
In the citing paper
“Although there have been no placebo-controlled trials in children, observational studies have suggested that early treatment can reduce LDL-C burden, improve endothelial function, substantially attenuate the development of atherosclerosis, and improve coronary outcomes [369-371].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [371]
In the citing paper
“Oestrogen replacement therapy, despite some favourable effects on the lipid profile, has not been demonstrated to reduce CV risk and cannot be recommended for CV prevention in women.166”
From ESC/EAS Guidelines for the management of dyslipidaemias (2011) · cites this paper as [166]
In the citing paper
“Oestrogen replacement therapy, despite some favourable effects on the lipid profile, has not been demonstrated to reduce CV risk and cannot be recommended for CVD prevention in women. 318”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [318]
In the citing paper
“and the higher palatability and acceptance of MeDiets in comparison with low-fat diets 17,18 lend support to our hypothesis.”
From Cohort Profile: Design and methods of the PREDIMED study (2012) · cites this paper as [18]
In the citing paper
“Oestrogen replacement therapy, despite some favourable effects on the lipid profile, has not been demonstrated to reduce CV risk and cannot be recommended for CVD prevention in women.318”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [318]
In the citing paper
“however, hormone replacement therapy does not consistently restore BP, suggesting additional regulatory mechanisms [ 177 ].”
From Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications (2026) · cites this paper as [177]
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Citations
Cites
Regression Models and Life-Tables
Cox, D. R. (1972) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1972.tb00899.x · Cited by 39,793
Writing Group for the Women's Health Initiative Investigators (2002) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.288.3.321 · Cited by 15,889
Hulley, S. (1998) · JAMA · doi:10.1001/jama.280.7.605 · Cited by 6,216
The Protective Effects of Estrogen on the Cardiovascular System
Mendelsohn, M. E., & Karas, R. H. (1999) · New England Journal of Medicine · doi:10.1056/nejm199906103402306 · Cited by 3,119
Grundy, S. M., Benjamin, I. J., Burke, G. L., Chait, A., Eckel, R. H., Howard, B. V., Mitch, W., Smith, S. C., & Sowers, J. R. (1999) · Circulation · doi:10.1161/01.cir.100.10.1134 · Cited by 2,698
Design of the Women’s Health Initiative Clinical Trial and Observational Study
The Women’s Health Initiative Study Group (1998) · Controlled Clinical Trials · doi:10.1016/s0197-2456(97)00078-0 · Cited by 2,580
Hormone Therapy To Prevent Disease and Prolong Life in Postmenopausal Women
Grady, D., Rubin, S. M., Petitti, D. B., Fox, C. S., Black, D. M., Ettinger, B. B., Ernster, V. L., & Cummings, S. R. (1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-117-12-1016 · Cited by 2,329
Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy
Grady, D. G., Herrington, D. M., Bittner, V., Blumenthal, R. S., Davidson, M., Hlatky, M. A., Hsia, J. A., Hulley, S. B., Herd, A. J., Khan, S. S., et al. (2002) · JAMA · doi:10.1001/jama.288.1.49 · Cited by 1,921
Self-citationEffect of Statin Therapy on C-Reactive Protein Levels
Albert, M. A., Danielson, E., Rifai, N., Ridker, P. M., & for the PRINCE Investigators (2001) · JAMA · doi:10.1001/jama.286.1.64 · Cited by 1,644
Effects of Estrogen Replacement on the Progression of Coronary-Artery Atherosclerosis
Herrington, D. M., Reboussin, D. M., Brosnihan, K. B., Sharp, P. C., Shumaker, S. A., Snyder, T. E., Furberg, C. D., Kowalchuk, G. J., Stuckey, T. D., Rogers, W. J., et al. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008243430801 · Cited by 1,242
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Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L., Jones, D. W., Materson, B. J., Oparil, S., Wright, J. T., et al. (2003) · Hypertension · doi:10.1161/01.hyp.0000107251.49515.c2 · Cited by 13,271
Self-citationMach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961
2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes
Knuuti, J., Wijns, W., Saraste, A., Capodanno, D., Barbato, E., Funck-Brentano, C., Prescott, E., Storey, R. F., Deaton, C., Cuisset, T., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz425 · Cited by 7,166
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854
Metadata
- Authors
- Manson, J. E., Hsia, J., Johnson, K. C., Rossouw, J. E., Assaf, A. R., Lasser, N. L., Trevisan, M., Black, H. R., Heckbert, S. R., Detrano, R., Strickland, O. L., Wong, N. D., Crouse, J. R., Stein, E., & Cushman, M.
- Affiliations
- Brigham and Women's Hospital (US)
- George Washington University (US)
- University of Tennessee Health Science Center (US)
- National Heart, Lung, and Blood Institute (US)
- Memorial Hospital of Rhode Island (US)
- Rutgers New Jersey Medical School (US)
- University at Buffalo, State University of New York (US)
- Rush University Medical Center (US)
- University of Washington (US)
- University of California, Los Angeles (US)
- Emory University (US)
- University of California, Irvine (US)
- Wake Forest University (US)
- University of Vermont (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-08-07
- Volume
- 349
- Issue
- 6
- Pages
- 523-534
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1981922048
- Cited by
- 2,065
- References
- 35
- Citations by year
- 2026: 32 · 2025: 43 · 2024: 34 · 2023: 32 · 2022: 33 · 2021: 43 · 2020: 51 · 2019: 48 · 2018: 51 · 2017: 59 · 2016: 42 · 2015: 67 · 2014: 73 · 2013: 109 · 2012: 99
- FWCI
- 123.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- estrogen plus progestin, coronary artery disease, hormone replacement therapy, Women's Health Initiative, postmenopausal women, conjugated equine estrogens, medroxyprogesterone acetate, myocardial infarction, cardiovascular risk, LDL cholesterol, C-reactive protein, trial termination
- MeSH terms
- Aged, Coronary Disease, Double-Blind Method, Drug Combinations, Estrogens, Conjugated (USP), Female, Follow-Up Studies, Heart Diseases, Humans, Middle Aged, Myocardial Infarction, Risk Factors, Proportional Hazards Models, Case-Control Studies, Treatment Outcome, Medroxyprogesterone Acetate, Postmenopause, Hormone Replacement Therapy, Progesterone Congeners
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