A “window of opportunity:” the reduction of coronary heart disease and total mortality with menopausal therapies is age- and time-dependent
Open accessAbstract
The totality of data indicates that the "window of opportunity" for reducing coronary heart disease (CHD) and overall mortality is initiation of hormone therapy (HT) within 6 years of menopause and/or before 60 years of age. Reduction of CHD risk and overall mortality with prolonged HT use in this subgroup of women is consistent across randomized controlled trials and observational studies. As such, HT use for 5 to 30 years in postmenopausal women who initiate HT in their 50s substantially increases quality-adjusted life-years (QALYs) by 1.5 QALYs and is highly cost-effective at $2438 per QALY gained. Cumulated randomized controlled trial results indicate a consistency along with observational data that young postmenopausal women with menopausal symptoms who use HT for long periods of time have lower rates of CHD and overall mortality than comparable postmenopausal women who do not use HT.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944 · see citing works
Expert Panel on Detection, E. (2001) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.285.19.2486 · Cited by 26,011 · see citing works
Hulley, S. (1998) · JAMA · doi:10.1001/jama.280.7.605 · Cited by 6,216 · see citing works
Estrogen plus Progestin and the Risk of Coronary Heart Disease
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., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030808 · Cited by 2,065 · see citing works
A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women
Ridker, P. M., Cook, N. R., Lee, I.-M., Gordon, D., Gaziano, J. M., Manson, J. E., Hennekens, C. H., & Buring, J. E. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050613 · Cited by 1,945 · see citing works
Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause
Rossouw, J. E., Prentice, R. L., Manson, J. E., Wu, L., Barad, D., Barnabei, V. M., Ko, M., LaCroix, A. Z., Margolis, K. L., & Stefanick, M. L. (2007) · JAMA · doi:10.1001/jama.297.13.1465 · Cited by 1,741 · see citing works
Postmenopausal Estrogen and Progestin Use and the Risk of Cardiovascular Disease
Grodstein, F., Stampfer, M. J., Manson, J. E., Colditz, G. A., Willett, W. C., ROSNER, B. A., Speizer, F. E., & Hennekens, C. H. (1996) · New England Journal of Medicine · doi:10.1056/nejm199608153350701 · Cited by 1,294 · see citing works
Grodstein, F., Manson, J. E., Colditz, G. A., Willett, W. C., Speizer, F. E., & Stampfer, M. J. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-133-12-200012190-00008 · Cited by 1,063 · see citing works
Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women
Mosca, L. J., Appel, L. J., Benjamin, E. J., Berra, K. A., Chandra‐Strobos, N., Fabunmi, R. P., Grady, D. G., Haan, C. K., Hayes, S. N., Judelson, D. R., et al. (2004) · Circulation · doi:10.1161/01.cir.0000114834.85476.81 · Cited by 917 · see citing works
Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men
Berger, J. S., Roncaglioni, M. C., Avanzini, F., Pangrazzi, I., Tognoni, G., & Brown, D. (2006) · JAMA · doi:10.1001/jama.295.3.306 · Cited by 781 · see citing works
Estrogen Therapy and Coronary-Artery Calcification
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., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa071513 · Cited by 711 · see citing works
Estrogen in the Prevention of Atherosclerosis
Hodis, H. N., Mack, W. J., Lobo, R. A., Shoupe, D., Sevanian, A., Mahrer, P. R., Selzer, R. H., Liu, C., Ci-hua, L., & Azen, S. P. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-135-11-200112040-00005 · Cited by 688 · see citing works
Self-citationDecreased Mortality in Users of Estrogen Replacement Therapy
HENDERSON, B. E. (1991) · Archives of Internal Medicine · doi:10.1001/archinte.1991.00400010095012 · Cited by 634 · see citing works
Conjugated Equine Estrogens and Coronary Heart Disease
Hsia, J. A. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.3.357 · Cited by 604 · see citing works
The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women
Grodstein, F., & Stampfer, M. J. (1995) · Progress in Cardiovascular Diseases · doi:10.1016/s0033-0620(95)80012-3 · Cited by 417 · see citing works
Freeman, M. R., Schneck, F. X., Gagnon, M. L., Corless, C. L., Söker, S., Niknejad, K., Peoples, G. E., & Klagsbrun, M. (1995) · PubMed · Cited by 393 · see citing works
Hormone Therapy and the Progression of Coronary-Artery Atherosclerosis in Postmenopausal Women
Hodis, H. N., Mack, W. J., Azen, S. P., Lobo, R. A., Shoupe, D., Mahrer, P. R., Faxon, D. P., Cashin-Hemphill, L., Sanmarco, M. E., French, W. J., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030830 · Cited by 386 · see citing works
Self-citationSalpeter, S. R., Walsh, J. M. E., Greyber, E., & Salpeter, E. E. (2006) · Journal of General Internal Medicine · doi:10.1111/j.1525-1497.2006.00389.x · Cited by 362 · see citing works
Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women
Mosca, L. J., Appel, L. J., Benjamin, E. J., Berra, K. A., Chandra‐Strobos, N., Fabunmi, R. P., Grady, D. G., Haan, C. K., Hayes, S. N., Judelson, D. R., et al. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000114834.85476.81 · Cited by 342 · see citing works
The risk of acute myocardial infarction after oestrogen and oestrogen‐progestogen replacement
Falkeborn, M., Persson, I. R., Adami, H., Bergström, R., Eaker, E. D., Lithell, H., Mohsen, R., & Naessén, T. (1992) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1992.tb14414.x · Cited by 334 · see citing works
Psaty, B. M. (1994) · Archives of Internal Medicine · doi:10.1001/archinte.154.12.1333 · Cited by 301 · see citing works
Mortality associated with hormone replacement therapy in younger and older women
Salpeter, S. R., Walsh, J. M. E., Greyber, E., Ormiston, T. M., & Salpeter, E. E. (2004) · Journal of General Internal Medicine · doi:10.1111/j.1525-1497.2004.30281.x · Cited by 292 · see citing works
Drug Treatment of Hyperlipidemia in Women
Walsh, J. M. E. (2004) · JAMA · doi:10.1001/jama.291.18.2243 · Cited by 270 · see citing works
Prentice, R. L., Langer, R., Stefanick, M. L., Howard, B. V., Pettinger, M. B., Anderson, G. L., Barad, D. H., Curb, J. D., Kotchen, J. M., Kuller, L. H., et al. (2005) · American Journal of Epidemiology · doi:10.1093/aje/kwi223 · Cited by 261 · see citing works
George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis reversal.
Blankenhorn, D. H., & Hodis, H. (1994) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.14.2.177 · Cited by 226 · see citing works
Self-citationBayesian Meta-analysis of Hormone Therapy and Mortality in Younger Postmenopausal Women
Salpeter, S. R., Cheng, J., Thabane, L., Buckley, N. S., & Salpeter, E. E. (2009) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.05.021 · Cited by 201 · see citing works
Psaty, B. M. (1994) · Archives of Internal Medicine · doi:10.1001/archinte.1994.00420120047005 · Cited by 196 · see citing works
Prentice, R. L., Langer, R. D., Stefanick, M. L., Howard, B. V., Pettinger, M. B., Anderson, G. L., Barad, D. H., Curb, J. D., Kotchen, J. M., Kuller, L. H., et al. (2006) · American Journal of Epidemiology · doi:10.1093/aje/kwj079 · Cited by 160 · see citing works
Petretta, M., Costanzo, P., Perrone-Filardi, P., & Chiariello, M. (2010) · International Journal of Cardiology · doi:10.1016/j.ijcard.2008.08.001 · Cited by 141 · see citing works
The use of hormonal replacement therapy and the risk of stroke and myocardial infarction in women.
Thompson, S. G., Meade, T. W., & Greenberg, G. M. (1989) · Journal of Epidemiology & Community Health · doi:10.1136/jech.43.2.173 · Cited by 117 · see citing works
Toh, S., Hernández–Dı́az, S., Logan, R., Rossouw, J. E., & Hernán, M. Á. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-152-4-201002160-00005 · Cited by 111 · see citing works
Heckbert, S. R. (1997) · Archives of Internal Medicine · doi:10.1001/archinte.1997.00440330066007 · Cited by 109 · see citing works
Collins, P. D., Mosca, L. J., Geiger, M. J., Grady, D. G., Kornitzer, M., Amewou-Atisso, M. G., Effron, M. B., Dowsett, S. A., Barrett-Connor, E. L., & Wenger, N. K. (2009) · Circulation · doi:10.1161/circulationaha.108.817577 · Cited by 107 · see citing works
The Cost-effectiveness of Hormone Therapy in Younger and Older Postmenopausal Women
Salpeter, S. R., Buckley, N. S., Liu, H., & Salpeter, E. E. (2008) · The American Journal of Medicine · doi:10.1016/j.amjmed.2008.07.026 · Cited by 75 · see citing works
Ferrara, A. M., Quesenberry, C. P., Karter, A. J., Njoroge, C. W., Jacobson, A. S., & Selby, J. V. (2003) · Circulation · doi:10.1161/01.cir.0000042701.17528.95 · Cited by 73 · see citing works
Estrogen for women at varying risk of coronary disease
Grodstein, F., & Stampfer, M. J. (1998) · Maturitas · doi:10.1016/s0378-5122(98)00055-3 · Cited by 68 · see citing works
Hormone Replacement Therapy Is Associated with Less Coronary Atherosclerosis in Postmenopausal Women
Akhrass, F., Evans, A. T., Wang, Y., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031008 · Cited by 63 · see citing works
Postmenopausal hormone therapy in clinical perspective
Hodis, H. N., & Mack, W. J. (2007) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e31802e8508 · Cited by 49 · see citing works
Self-citationBarrett-Connor, E. L., & Laughlin, G. A. (2005) · Menopause The Journal of The North American Menopause Society · doi:10.1097/00042192-200512010-00009 · Cited by 46 · see citing works
Chilvers, C. E. D. (2003) · European Heart Journal · doi:10.1016/j.ehj.2003.09.019 · Cited by 46 · see citing works
de Kleijn, M. J. J., Bots, M. L., Bak, A. A. A., Westendorp, I. C. D., Planellas, J., Bennink, H. J. T. C., Witteman, J. C. M., & Grobbee, D. E. (1999) · Maturitas · doi:10.1016/s0378-5122(99)00035-3 · Cited by 46 · see citing works
Postmenopausal Hormone Therapy and Cardiovascular Disease in Perspective
Hodis, H. N., & Mack, W. J. (2008) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0b013e318181de86 · Cited by 41 · see citing works
Self-citationTreatment of the Postmenopausal Woman
(2007) · Elsevier eBooks · doi:10.1016/b978-0-12-369443-0.x5000-5 · Cited by 37 · see citing works
Hodis, H. N., & Mack, W. J. (2007) · Elsevier eBooks · doi:10.1016/b978-012369443-0/50047-8 · Cited by 6 · see citing works
Self-citationNonhormonal Therapies for Menopausal Hot Flashes: Systematic Review and Meta-analysis
Nelson, H. D., Vesco, K. K., Haney, E., Fu, R., Nedrow, A., Miller, J., Nicolaidis, C., Walker, M., & Humphrey, L. (2006) · JAMA · doi:10.1001/jama.295.17.2057 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Understanding the broad influence of sex hormones and sex differences in the brain
McEwen, B. S., & Milner, T. A. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23809 · Cited by 642 · see citing works
Soy and Health Update: Evaluation of the Clinical and Epidemiologic Literature
Messina, M. (2016) · Nutrients · doi:10.3390/nu8120754 · Cited by 537 · see citing works
Effects of transdermal versus oral hormone replacement therapy in postmenopause: a systematic review
Goldštajn, M. Š., Mikuš, M., Ferrari, F. A., Bosco, M., Uccella, S., Noventa, M., Török, P., Terzic, S., Laganà, A. S., & Garzon, S. (2022) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-022-06647-5 · Cited by 111 · see citing works
Udeh-Momoh, C., & Watermeyer, T. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101459 · Cited by 67 · see citing works
Lee, A. A., & Den Hartigh, L. J. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1682231 · Cited by 32 · see citing works
“Developing therapies require the precision of understanding the interplay between the human hormonal milieu and metabolic health to manage metabolic dysfunction in diverse populations.”
S-Equol, an Antioxidant Metabolite of Soy Daidzein, and Oxidative Stress in Aging
Jackson, R. L., Greiwe, J. S., & Schwen, R. J. (2014) · Aging · doi:10.1016/b978-0-12-405933-7.00015-9 · Cited by 4 · see citing works
- Authors
- Hodis, H. N., & Mack, W. J.
- Affiliations
- University of Southern California (US)
- ORCID
- Mack, Wendy J.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 1379
- Pages
- 244-252
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC3046231
- OpenAlex
- W2161123157
- Cited by
- 83
- References
- 46
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 9 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 8 · 2012: 6
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01AG-024154)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- hormone replacement therapy, coronary artery disease, all-cause mortality, window of opportunity, postmenopausal women, age at menopause, treatment duration, quality-adjusted life years, cost-effectiveness, menopausal symptoms
- MeSH terms
- Age Factors, Animals, Coronary Disease, Female, Humans, Menopause, Time Factors, Estrogen Replacement Therapy, Randomized Controlled Trials as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review