Cited by 779Menopause: Health Impacts and TreatmentsEstrogen and related hormone effectsHormonal and reproductive studies

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

Open access

Hodis, Howard N., Mack, Wendy J., Henderson, Victor W., Shoupe, Donna, Budoff, Matthew J., Hwang-Levine, Juliana, Li, Yanjie, Feng, Mei, Dustin, Laurie, Kono, Naoko, Stanczyk, Frank Z., Selzer, Robert H., Azen, Stanley P.·2016·New England Journal of Medicine

DOI 10.1056/nejmoa1505241PMC PMC4921205

Open this paper in CoChat — free account Open PDF

Abstract

BACKGROUND: Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. METHODS: A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. RESULTS: After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. CONCLUSIONS: Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.).

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

Crossref · 10.1056/nejmoa1505241

Cites

42 of 42 references verified0 citation errors · 0 not checkable

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.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A Simple Sequentially Rejective Multiple Test Procedure
(1979) · Scandinavian Journal of Statistics · doi:10.2307/4615733 · Cited by 21,526
A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association
Wg, A., Edwards, J., Frye, R., Gg, G., Gott, V. L., Griffith, L., McGoon, D. C., Murphy, M., & Roe, B. B. (1975) · Circulation · doi:10.1161/01.cir.51.4.5 · Cited by 3,255
Diagnostic Performance of 64-Multidetector Row Coronary Computed Tomographic Angiography for Evaluation of Coronary Artery Stenosis in Individuals Without Known Coronary Artery Disease
Budoff, M. J., Dowe, D. A., Jollis, J. G., Gitter, M. J., Sutherland, J., Halamert, E., Scherer, M. D., Bellinger, R. L., Martin, A., Benton, R., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.07.031 · Cited by 2,121
Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials
Manson, J. E., Chlebowski, R. T., Stefanick, M. L., Aragaki, A. K., Rossouw, J. E., Prentice, R. L., Anderson, G., Howard, B. V., Thomson, C. A., LaCroix, A. Z., et al. (2013) · JAMA · doi:10.1001/jama.2013.278040 · Cited by 1,650
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
The Role of Carotid Arterial Intima-Media Thickness in Predicting Clinical Coronary Events
Hodis, H. N., Mack, W. J., LaBree, L., Selzer, R. H., Liu, C.-R., Liu, C.-H., & Azen, S. P. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-4-199802150-00002 · Cited by 1,217
Calcified Coronary Artery Plaque Measurement with Cardiac CT in Population-based Studies: Standardized Protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) Study
Carr, J. J., Nelson, J. C., Wong, N. D., McNitt‐Gray, M. F., Arad, Y., Jacobs, D. R., Sidney, S., Bild, D. E., Williams, O. D., & Detrano, R. (2005) · Radiology · doi:10.1148/radiol.2341040439 · Cited by 855
Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial
Schierbeck, L. L., Rejnmark, L., Tofteng, C. L., Stilgren, L. S., Eiken, P., Mosekilde, L., Køber, L., & Jensen, J. B. (2012) · BMJ · doi:10.1136/bmj.e6409 · Cited by 753
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
Estrogen Improves Endothelium-Dependent, Flow-Mediated Vasodilation in Postmenopausal Women
Lieberman, E. H., Gerhard, M. D., Uehata, A., Walsh, B. W., Selwyn, A. P., Ganz, P., Yeung, A. C., & Creager, M. A. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-121-12-199412150-00005 · Cited by 701

Flagged first, then by citations

Show all 42 references

Research works printed but not linked: 2

Holm S, 1979, Scand J Stat, 6, 65
Boardman HM, 2015, Cochrane Database Syst Rev, CD002229

Sorted by citations

Items 101–200 of 775

Estrogen-SIRT1 Axis Plays a Pivotal Role in Protecting Arteries Against Menopause-Induced Senescence and Atherosclerosis
Sasaki, Y., Ikeda, Y., Miyauchi, T., Uchikado, Y., Akasaki, Y., & Ohishi, M. (2019) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.47993 · Cited by 75
Age at menopause and risk of heart failure and atrial fibrillation: a nationwide cohort study
Shin, J., Han, K., Jung, J., Park, H., Kim, W., Huh, Y., Kim, Y., Kim, D., Kim, S. M., Choi, Y. S., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac364 · Cited by 77
Estrogens and Coronary Artery Disease
Meyer, M. R., & Barton, M. (2016) · Advances in pharmacology · doi:10.1016/bs.apha.2016.05.003 · Cited by 79
Postmenopausal health interventions: Time to move on from the Women’s Health Initiative?
Zaw, J. J. T., Howe, P. R. C., & Wong, R. H. X. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.10.005 · Cited by 74
Estrogen Contributions to Microvascular Dysfunction Evolving to Heart Failure With Preserved Ejection Fraction
Sickinghe, A. A., Korporaal, S. J. A., den Ruijter, H. M., & Kessler, E. L. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00442 · Cited by 75
“The risks of HT outweighed the benefits in all age groups (81).”
Background
The Critical Period for Neuroprotection by Estrogen Replacement Therapy and the Potential Underlying Mechanisms
Guo, H., Liu, M., Zhang, L., Wang, L., Hou, W., Ma, Y., & Ma, Y. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200123165652 · Cited by 74
Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons
Gartlehner, G., Patel, S. V., Reddy, S., Rains, C. B., Coker-Schwimmer, M. J. L., & Kahwati, L. C. (2022) · JAMA · doi:10.1001/jama.2022.18324 · Cited by 85
Menopausal Hormone Therapy and Cardiovascular Risk: Where are we Now?
Anagnostis, P. G., Paschou, S. Α., Katsiki, N., Krikidis, D., Lambrinoudaki, I. V., & Goulis, D. G. (2018) · Current Vascular Pharmacology · doi:10.2174/1570161116666180709095348 · Cited by 78
A roadmap for sex- and gender-disaggregated health research
Peters, S. A. E., & Woodward, M. (2023) · BMC Medicine · doi:10.1186/s12916-023-03060-w · Cited by 84
“It now seems that timing is critical, and the benefits only seem to be present when the therapy is initiated temporally close to menopause and not when initiated later [74].”
Background
Recent Progress in Vascular Aging: Mechanisms and Its Role in Age-related Diseases
Xu, X., Wang, B. Z., Ren, C., Hu, J., Greenberg, D. A., Chen, T., Xie, L., & Jin, K. (2017) · Aging and Disease · doi:10.14336/ad.2017.0507 · Cited by 72
“However, some evidence suggest that estrogen can delay the progression of atherosclerotic lesions, measured by carotid artery intima-media thickness, in early postmenopausal women [123].”
Background
Arterial structure and function during and after long-duration spaceflight
Lee, S. M. C., Ribeiro, L. C., Martin, D. S., Zwart, S. R., Feiveson, A. H., Laurie, S. S., Macias, B. R., Crucian, B. E., Krieger, S., Weber, D., et al. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00550.2019 · Cited by 76
Cardiovascular risk in menopausal women and our evolving understanding of menopausal hormone therapy: risks, benefits, and current guidelines for use
Prabakaran, S., Schwartz, A. M., & Lundberg, G. P. (2021) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188211013917 · Cited by 83
Exploring the effects of estrogen deficiency and aging on organismal homeostasis during menopause
Camon, C., Garratt, M., & Correa, S. M. (2024) · Nature Aging · doi:10.1038/s43587-024-00767-0 · Cited by 84
“…improve CVD that has already been established in older postmenopausal research participants, as shown in the Early versus Late Intervention Trial with Estradiol (ELITE) study, a randomized, double-blinded, placebo-controlled trial examining atherosclerotic plaque progression during menopause 142 .”
Update on hormone therapy for the management of postmenopausal women
Pan, M., Pan, X., Zhou, J., Wang, J., Qi, Q., & Wang, L. (2022) · BioScience Trends · doi:10.5582/bst.2021.01418 · Cited by 73
“studies (7-9), international societies and organizations such as the International Menopause Society (IMS), the North American Menopause Society (NAMS), the European Menopause and Andropause Society (EMAS) have formulated guidelines and announced consensus opinions on the use of HT.”
Background
Sex differences in the inflammatory response to stroke
Tariq, M. B., Lee, J., & McCullough, L. D. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00969-x · Cited by 72
“Ongoing clinical trials that enrolled women at the time of menopause are currently ongoing [105, 106].”
Background
Advances in the management of osteoporosis
Hoong, C. W. S., Saul, D., Khosla, S., & Sfeir, J. G. (2025) · BMJ · doi:10.1136/bmj-2024-081250 · Cited by 77
“111 112-115 In the past decade, the availability of 17 β -estradiol, transdermal estrogens, and ultra low dose formulations has further mitigated risks of thromboembolism while maintaining gains in BMD. 116 117 The use of HRT or tibolone is currently limited to women 60 years with vasomotor or…”
Estrogen Receptor Control of Atherosclerotic Calcification and Smooth Muscle Cell Osteogenic Differentiation
McRobb, L. S., McGrath, K. C. Y., Tsatralis, T., Liong, E. C., Tan, J. T. M., Hughes, G., Handelsman, D. J., & Heather, A. K. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309054 · Cited by 68
Menopause in CKD
Vellanki, K., & Hou, S. (2018) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2017.12.019 · Cited by 68
Gaps, limitations and new insights on endogenous estrogen and follicle stimulating hormone as related to risk of cardiovascular disease in women traversing the menopause: A narrative review
Khoudary, S. R. E. (2017) · Maturitas · doi:10.1016/j.maturitas.2017.08.003 · Cited by 66
Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs
Fuggle, N. R., Cooper, C. C., Harvey, N. C., Al‐Daghri, N. M., Brandi, M. L., Bruyère, O., Cano, A., Dennison, E. M., Díez‐Pérez, A., Kaufman, J., et al. (2020) · Drugs · doi:10.1007/s40265-020-01364-2 · Cited by 68
Sex differences in abdominal aortic aneurysms
Boese, A. C., Chang, L., Yin, K., Chen, Y. E., Lee, J., & Hamblin, M. H. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00519.2017 · Cited by 68
Ovarian steroid hormones: A long overlooked but critical contributor to brain aging and Alzheimer’s disease
Jett, S., Schelbaum, E., Jang, G., Boneu, C., Dyke, J. P., Pahlajani, S. S., Brinton, R. D., & Mosconi, L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.948219 · Cited by 66
“subclinical atherosclerosis when therapy was initiated soon after menopause (Hodis et al., 2016), which has been linked to a 30% reduced number of heart attacks and cardiac deaths (Salpeter”
Background
Role of estrogen in women's Alzheimer's disease risk as modified by APOE
Valencia‐Olvera, A. C., Weng, J. M., Christensen, A., LaDu, M. J., & Pike, C. J. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13209 · Cited by 75
Estrogen Receptor and Vascular Aging
Davezac, M., Buscato, M., Zahreddine, R., Lacolley, P. J., Henrion, D., Lenfant, F., Arnal, J., & Fontaine, C. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.727380 · Cited by 72
“Finally, the “timing hypothesis” was confirmed in 2016 by the Early versus Late Intervention Trial with Estradiol (ELITE) group results, showing beneficial effects of E2 therapy on carotid atherosclerosis in early (≤6 years) compared to late (≥10 years) menopausal women (Hodis et al., 2016).”
Result
Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets
Mericskay, M., Zuurbier, C. J., Heather, L. C., Karlstaedt, A., Inserte, J., Bertrand, L., Kararigas, G., Ruiz‐Meana, M., Maack, C., & Schiattarella, G. G. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01166-7 · Cited by 68
Anti-Atherosclerotic Effects of a Phytoestrogen-Rich Herbal Preparation in Postmenopausal Women
Myasoedova, V. A., Kirichenko, T. V., Melnichenko, A. А., Orekhova, V. A., Ravani, A. L., Poggio, P., Sobenin, I. A., Bobryshev, Y. V., & Orekhov, A. N. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081318 · Cited by 65
Physiologically assessed hot flashes and endothelial function among midlife women
Thurston, R. C., Chang, Y., Barinas‐Mitchell, E., Jennings, J. R., von Känel, R., Landsittel, D., & Matthews, K. A. (2017) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000857 · Cited by 61
Regulatory Actions of Estrogen Receptor Signaling in the Cardiovascular System
Ueda, K., Adachi, Y., Liu, P., Fukuma, N., & Takimoto, E. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00909 · Cited by 60
“However, recent clinical trials and meta-analyses have suggested that estrogen treatment has beneficial effects for preventing CVD and does not affect mortality if HT is initiated early after menopause (6, 11).”
BackgroundMethodInfluential
A Review of Hormone and Non-Hormonal Therapy Options for the Treatment of Menopause
Madsen, T. E., Sobel, T., Negash, S., Shrout, T. A., Stefanick, M. L., Manson, J. E., & Allison, M. (2023) · International Journal of Women s Health · doi:10.2147/ijwh.s379808 · Cited by 78
“sclerosis compared with placebo when started within 6 years of menopause but not when MHT was started more than 10 years since menopause.(60) These findings support the hypothesis and support current recommendations that the benefits of MHT for VMS likely outweigh risks for women if started less than 10 years after me…”
Result
Early Postmenopausal Phase Is Associated With Reduced Prostacyclin-Induced Vasodilation That Is Reversed by Exercise Training
Nyberg, M., Egelund, J., Mandrup, C. M., Nielsen, M. B., Mogensen, A. S., Stallknecht, B. M., Bangsbo, J., & Hellsten, Y. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07866 · Cited by 59
“Along these lines, the beneficial effects of estrogen supplementation in terms of atherosclerosis and cardiovascular disease are most pronounced during the peri- and early postmenopausal years when estrogen receptors (ERs) or other compensatory mechanisms may function.(17,18) To what extent the beneficial effects of e…”
Background
An update on hormone therapy in postmenopausal women: mini-review for the basic scientist
Miller, V. M., & Harman, S. M. (2017) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00383.2017 · Cited by 56
The Canadian Women’s Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women — Chapter 4: Sex- and Gender-Unique Disparities: CVD Across the Lifespan of a Woman
Mulvagh, S. L., Mullen, K., Nerenberg, K. A., Kirkham, A. A., Green, C. R., Dhukai, A. R., Grewal, J., Hardy, M., Harvey, P., Ahmed, S. B., et al. (2021) · CJC Open · doi:10.1016/j.cjco.2021.09.013 · Cited by 62
Alzheimer’s disease, apolipoprotein E and hormone replacement therapy
Depypere, H. T., Vierin, A., Weyers, S., & Sieben, A. (2016) · Maturitas · doi:10.1016/j.maturitas.2016.09.009 · Cited by 60
Sex hormones and stroke: Beyond estrogens
Sohrabji, F., Okoreeh, A. K., & Panta, A. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.10.010 · Cited by 59
Estrogen-Mediated Gaseous Signaling Molecules in Cardiovascular Disease
Teoh, J., Li, X., Simoncini, T., Zhu, D., & Fu, X. (2020) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2020.06.001 · Cited by 57
Estrogen Receptors: Therapeutic Perspectives for the Treatment of Cardiac Dysfunction after Myocardial Infarction
da Silva, J. S., Montagnoli, T. L., Rocha, B., Tacco, M. L. C. A., Marinho, S. C. P., & Zapata‐Sudo, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020525 · Cited by 59
Postmenopausal hormone therapy and risk of stroke: A pooled analysis of data from population-based cohort studies
Carrasquilla, G. D., Frumento, P., Berglund, A., Borgfeldt, C., Bottai, M., Chiavenna, C., Eliasson, M., Engström, G., Hallmans, G., Jansson, J., et al. (2017) · PLoS Medicine · doi:10.1371/journal.pmed.1002445 · Cited by 55
Menopausal Hormone Therapy and Long-Term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials
Manson, J. E., Aragaki, A. K., Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Chlebowski, R. T., Howard, B. V., Thomson, C. A., Margolis, K. L., et al. (2018) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000527868.87744.14 · Cited by 54
Sex–Gender Disparities in Cardiovascular Diseases: The Effects of Estrogen on eNOS, Lipid Profile, and NFATs During Catecholamine Stress
Noah, M. L. N., Adzika, G. K., Mprah, R., Adekunle, A. O., Adu‐Amankwaah, J., & Sun, H. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.639946 · Cited by 56
Sex and Gender: Critical Variables in Pre-Clinical and Clinical Medical Research
Morselli, E., Frank, A. P., Santos, R. D. S., de Fátima, L. A., Palmer, B. F., & Clegg, D. J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.017 · Cited by 56
Endogenous Sex Hormones and Endothelial Function in Postmenopausal Women and Men: The Multi-Ethnic Study of Atherosclerosis
Mathews, L. M., Subramanya, V., Zhao, D., Ouyang, P., Vaidya, D. M., Güallar, E., Yeboah, J., Herrington, D. M., Hays, A. G., Budoff, M. J., et al. (2019) · Journal of Women s Health · doi:10.1089/jwh.2018.7441 · Cited by 60
Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System
Ueda, K., Fukuma, N., Adachi, Y., Numata, G., Tokiwa, H., Toyoda, M., Otani, A., Hashimoto, M., Liu, P., & Takimoto, E. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.738218 · Cited by 57
Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high‐intensity exercise training are enhanced in the early postmenopausal phase
Nyberg, M., Egelund, J., Mandrup, C. M., Roland, C. B., Hansen, K. M., Hergel, I.-M., Valbak‐Andersen, N., Frikke‐Schmidt, R., Stallknecht, B. M., Bangsbo, J., et al. (2017) · The Journal of Physiology · doi:10.1113/jp273871 · Cited by 52
“…by physiological changes associated with the transition from the pre- to the early perimenopausal phase because these changes may lead to compensatory vascular mechanisms and consequently enhanced exercise hyperaemia during the menopausal transition (Clarkson et al. 2013; Hodis et al. 2016).”
Background
Estrogen, menopause, and Alzheimer’s disease: understanding the link to cognitive decline in women
Mervosh, N. L., & Devi, G. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1634302 · Cited by 62
Estrogenic vascular effects are diminished by chronological aging
Nicholson, C., Sweeney, M., Robson, S. C., & Taggart, M. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-12153-5 · Cited by 51
Estrogen Plays a Crucial Role in Rab9‐Dependent Mitochondrial Autophagy, Delaying Arterial Senescence
Sasaki, Y., Ikeda, Y., Uchikado, Y., Akasaki, Y., Sadoshima, J., & Ohishi, M. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.019310 · Cited by 52
Alisol B 23-acetate adjusts bile acid metabolisim via hepatic FXR-BSEP signaling activation to alleviate atherosclerosis
Fu, Y., Feng, H., Ding, X., Meng, Q.-H., Zhang, S.-R., Li, J., Chao, Y., Ji, T., Bi, Y., Zhang, W., et al. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154120 · Cited by 54
Effects of oral conjugated equine estrogens with or without medroxyprogesterone acetate on incident hypertension in the Women's Health Initiative hormone therapy trials
Swica, Y., Warren, M. P., Manson, J. E., Aragaki, A. K., Bassuk, S. S., Shimbo, D., Kaunitz, A. M., Rossouw, J. E., Stefanick, M. L., & Womack, C. R. (2018) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001067 · Cited by 51
The Timing Hypothesis: Hormone Therapy for Treating Symptomatic Women During Menopause and Its Relationship to Cardiovascular Disease
Mehta, J. M., Chester, R. C., & Kling, J. M. (2018) · Journal of Women s Health · doi:10.1089/jwh.2018.7201 · Cited by 50
“7,8,13,14 The timing hypothesis posits that hormones started at the time of menopause may reduce cardio-vascular risk and events, whereas hormones started further from menopause can increase risk.”
Genetic, Molecular, and Cellular Determinants of Sex-Specific Cardiovascular Traits
Vaura, F. C., Palmu, J., Aittokallio, J., Kauko, A., & Niiranen, T. (2022) · Circulation Research · doi:10.1161/circresaha.121.319891 · Cited by 58
JCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease
Fujiyoshi, A., Kohsaka, S., Hata, J., Hara, M., Kai, H., Masuda, D., Miyamatsu, N., Nishio, Y., Ogura, M., Sata, M., et al. (2024) · Circulation Journal · doi:10.1253/circj.cj-23-0285 · Cited by 55
The exercise timing hypothesis: can exercise training compensate for the reduction in blood vessel function after menopause if timed right?
Gliemann, L., & Hellsten, Y. (2019) · The Journal of Physiology · doi:10.1113/jp277056 · Cited by 47
“A third potential reason for a timing effect could be the same as indicated in studies on hormone replacement therapy (Hodis et al. , 2016), that prevention of a decline in cardiovascular health may be more easily achieved than reversal of already established detrimental changes in the vascular…”
BackgroundMethodResultInfluential
Sex and Gender Aspects in Vascular Ageing – Focus on Epidemiology, Pathophysiology, and Outcomes
Seeland, U., Nemcsik, J., Lønnebakken, M. T., Kublickiene, K. R., Schluchter, H., Park, C. M., Pucci, G., Mozos, I. M., & Bruno, R. M. (2021) · Heart Lung and Circulation · doi:10.1016/j.hlc.2021.07.006 · Cited by 47
Risk for Venous Thromboembolism in Transgender Patients Undergoing Cross-Sex Hormone Treatment: A Systematic Review
Kotamarti, V. S., Greige, N., Heiman, A. J., Patel, A., & Ricci, J. A. (2021) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2021.04.006 · Cited by 45
Targeted basic research to highlight the role of estrogen and estrogen receptors in the cardiovascular system
Dworatzek, E., & Mahmoodzadeh, S. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.01.019 · Cited by 44
Impact of Different Visual Field Testing Paradigms on Sample Size Requirements for Glaucoma Clinical Trials
Wu, Z., & Medeiros, F. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-23220-w · Cited by 45
Safety and benefit considerations for menopausal hormone therapy
Pickar, J. H., Archer, D. F., Kagan, R., Pinkerton, J. V., & Taylor, H. S. (2017) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2017.1343298 · Cited by 44
“Postmenopausal women without CVD at baseline (n = 643) were randomized to daily oral estradiol with (if women had a uterus) or without (if no uterus) vaginal micronized progesterone gel for 10 days each month or to placebo; women were randomized according to time since menopause (<6 years, n = 271; ≥10 years, n = 372)…”
MethodResult
Jiangu granules ameliorate postmenopausal osteoporosis via rectifying bone homeostasis imbalance: A network pharmacology analysis based on multi-omics validation
Li, C., Lin, X., Lin, Y., Lin, Y., & Lin, H. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.155137 · Cited by 44
Estrogen Signaling in the Adrenal Cortex
Caroccia, B., Seccia, T. M., Barton, M., & Rossi, G. P. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07660 · Cited by 44
Ovarian steroids act as respiratory stimulant and antioxidant against the causes and consequences of sleep-apnea in women
Boukari, R., Laouafa, S., Ribon‐Demars, A., Bairam, A., & Joseph, V. (2017) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2017.01.013 · Cited by 46
Estradiol Therapy After Menopause Mitigates Effects of Stress on Cortisol and Working Memory
Herrera, A. Y., Hodis, H. N., Mack, W. J., & Mather, M. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00825 · Cited by 44
Assessing assumptions for statistical analyses in randomised clinical trials
Nielsen, E. E., Nørskov, A. K., Lange, T., Thabane, L., Wetterslev, J., Beyersmann, J., de Uña‐Álvarez, J., Torri, V., Billot, L., Putter, H., et al. (2019) · BMJ Evidence-Based Medicine · doi:10.1136/bmjebm-2019-111174 · Cited by 44
“This trial, however, did neither specify the nature of the alternative analyses nor report the results of these assessments in the main publication.(4)”
A Contemporary View of Menopausal Hormone Therapy
Levy, B. S., & Simon, J. A. (2024) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000005553 · Cited by 45
“In contrast to the KEEPS trial, the ELITE (Early Versus Late Postmenopausal Treatment With Estra-diol) 26 study did find significant benefit for oral estra-diol-17 b therapy on carotid intima – media thickness accumulation of plaque.”
Result
The British Menopause Society & Women’s Health Concern 2016 recommendations on hormone replacement therapy in menopausal women
Hamoda, H., Panay, N., Arya, R., Savvas, M., & on behalf of The British Menopause Society and Women’s Health Concern (2016) · Post Reproductive Health · doi:10.1177/2053369116680501 · Cited by 43
“The ‘Early versus Late Intervention Trial with Estradiol’ (ELITE) by Hodis et al. (2016) reported on the cardiovascular effects of HRT in relation to the timing of initiation of treatment.”
Background
Sex differences in acute cardiovascular care: a review and needs assessment
Vallabhajosyula, S., Verghese, D., Desai, V. K., Sundaragiri, P. R., & Miller, V. M. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab063 · Cited by 44
“onary calcification and carotid artery intima-medial thickening when treatment began within 5 years of menopause.(52,56) For women who”
Background
Reproductive Health as a Marker of Subsequent Cardiovascular Disease
Manson, J. E., & Woodruff, T. K. (2016) · JAMA Cardiology · doi:10.1001/jamacardio.2016.2662 · Cited by 41
Menopause: A Global Perspective and Clinical Guide for Practice
Voedisch, A. J., Dunsmoor-Su, R. F., & Kasirsky, J. (2021) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0000000000000639 · Cited by 49
Nitric oxide-heat shock protein axis in menopausal hot flushes: neglected metabolic issues of chronic inflammatory diseases associated with deranged heat shock response
Miragem, A. A., & de Bittencourt, P. I. H. (2017) · Human Reproduction Update · doi:10.1093/humupd/dmx020 · Cited by 39
17β-Estradiol nongenomically induces vascular endothelial H2S release by promoting phosphorylation of cystathionine γ-lyase
Xu, X., Yan, Q., Liu, X., Li, P., Li, X., Chen, Y., Simoncini, T., Liu, J., Zhu, D., & Fu, X. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008597 · Cited by 39
“The incidence and severity of cardiovascular disease (CVD)5 are significantly increased in postmenopausal women (1).”
MethodInfluential
Hyperuricemia and Endothelial Function: Is It a Simple Association or Do Gender Differences Play a Role in This Binomial?
Ciarambino, T., Crispino, P., & Giordano, M. (2022) · Biomedicines · doi:10.3390/biomedicines10123067 · Cited by 39
“Since females are more protected than males against major cardiovascular events, it has long been assumed that estrogen is able to genetically mediate and regulate the expression of eNOS in endothelial cells [47,74] Furthermore, the activation of the enzyme and the formation of NO can also occur through rapid signalin…”
Background
Menopause and Chronic Kidney Disease
Ahmed, S. B. (2017) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2017.05.013 · Cited by 38
Sex as a biological variable in the pathology and pharmacology of neurodegenerative and neurovascular diseases
Honarpisheh, P., & McCullough, L. D. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14675 · Cited by 41
“Women started on oestrogen‐based hormone therapy around the time of menopause have slower progression of atherosclerosis as measured by CIMT compared to placebo‐treated women (Hodis et al., 2016).”
Method
Bone and heart health in menopause
Nash, Z., Wattar, B. H. A., & Davies, M. C. (2022) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2022.03.002 · Cited by 43
Advances in diagnosis and treatment of perimenopausal syndrome
Chen, W., Chen, M., Tang, H., Wei, W., Shao, P., Dou, S., Wu, J., Lu, B., Shi, R., & Chen, J. (2023) · Open Life Sciences · doi:10.1515/biol-2022-0754 · Cited by 37
Hormone Therapy Use and Risk of Chronic Disease in the Nurses’ Health Study: A Comparative Analysis With the Women's Health Initiative
Bhupathiraju, S. N., Grodstein, F., ROSNER, B. A., Stampfer, M. J., Hu, F. B., Willett, W. C., & Manson, J. E. (2017) · American Journal of Epidemiology · doi:10.1093/aje/kwx131 · Cited by 37
“Still, there were no differences in coronary artery disease, assessed by coronary artery stenosis, after 5 years of therapy (45).”
Sex Hormones and Healthy Psychological Aging in Women
Navarro‐Pardo, E., Holland, C., & Cano, A. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00439 · Cited by 36
“The notion of a critical period for positive cognitive effect or avoidance of a negative impact on cognition or increase in dementia risk is mirrored in investigations of HT where HT is shown to be beneficial in the early peri- and post-menopausal period, but not in older women or those who may already have advanced a…”
Background
Estrogen-mediated protection against coronary heart disease: The role of the Notch pathway
Fortini, F., Sega, F. V. D., Caliceti, C., Lambertini, E., Pannuti, A., Peiffer, D. S., Balla, C., & Rizzo, P. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.02.008 · Cited by 37
Roles of Hormone Replacement Therapy and Menopause on Osteoarthritis and Cardiovascular Disease Outcomes: A Narrative Review
Mei, Y., Williams, J. S., Webb, E. K., Shea, A. K., MacDonald, M. J., & Al‐Khazraji, B. K. (2022) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2022.825147 · Cited by 37
“, more than 10 years after menopause) (110).”
Background
Ischemic stroke across sexes: What is the status quo?
Liberale, L., Carbone, F., Montecucco, F., Gebhard, C., Lüscher, T. F., Wegener, S., & Camici, G. G. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.05.001 · Cited by 37
Heart rate variability as a function of menopausal status, menstrual cycle phase, and estradiol level
Ramesh, S., James, M. T., Holroyd-Leduc, J. M., Wilton, S. B., Sola, D. Y., & Ahmed, S. B. (2022) · Physiological Reports · doi:10.14814/phy2.15298 · Cited by 42
Sex and stroke risk factors: A review of differences and impact
Hanna, M., Wabnitz, A., & Grewal, P. (2024) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2024.107624 · Cited by 49
Sex and sex steroids as determinants of cardiovascular risk
Cignarella, A., Bolego, C., & Barton, M. (2024) · Steroids · doi:10.1016/j.steroids.2024.109423 · Cited by 39
Cardiometabolic Effects of Endocrine Treatment of Estrogen Receptor–Positive Early Breast Cancer
Cheung, Y.-M. M., Ramchand, S. K., Yeo, B. J., & Grossmann, M. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00096 · Cited by 37
“10 years postmenopausal [8, 9], the so-called “timing hypothesis” [10].”
Improving clinical outcomes through attention to sex and hormones in research
Mielke, M. M., & Miller, V. M. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00531-z · Cited by 40
Menopausal hormone therapy for primary prevention: why the USPSTF is wrong
Langer, R. D., Simon, J. A., Pines, A., Løbo, R. A., Hodis, H. N., Pickar, J. H., Archer, D. F., Sarrel, P. M., & Utian, W. H. (2017) · Climacteric · doi:10.1080/13697137.2017.1362156 · Cited by 36
Link between Endometriosis, Atherosclerotic Cardiovascular Disease, and the Health of Women Midlife
Taşkın, Ö., Rikhraj, K. J. K., Tan, J., Sedlak, T., Rowe, T., & Bedaiwy, M. A. (2019) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2019.02.022 · Cited by 37
A Practical Guide to Gynecologic and Reproductive Health in Women Undergoing Hematopoietic Stem Cell Transplant
Murphy, J., McKenna, M. M., Abdelazim, S., Battiwalla, M., & Stratton, P. (2019) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2019.07.038 · Cited by 35
Menopausal hormone therapy: a better and safer future
Davey, D. A. (2018) · Climacteric · doi:10.1080/13697137.2018.1439915 · Cited by 34
Cerebrovascular disease in women
Kumar, A., & McCullough, L. D. (2021) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286420985237 · Cited by 35
Physiologically assessed hot flashes and endothelial function among midlife women
Thurston, R. C., Chang, Y., Barinas‐Mitchell, E., Jennings, J. R., von Känel, R., Landsittel, D., & Matthews, K. A. (2018) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001239 · Cited by 34
“Notably, effect modification by age is a frequent observation for relations between reproductive hormonal factors (eg, hormone therapy) and CVD risk in women.(22,44,45) The mechanisms that may link hot flashes to poorer endothelial function require elucidation.”
Sex-specific risk factors for cardiovascular disease in women-making cardiovascular disease real
Merz, C. N. B., Ramineni, T., & Leong, D. (2018) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000543 · Cited by 37
The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis
Muraca, M., & Cappariello, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228682 · Cited by 35
“Use is limited in early menopause, no more than 10 years, because of concerns about cardiovascular safety [35].”
Background
Age-Specific Sex Differences in Magnetic Resonance Imaging-Depicted Carotid Intraplaque Hemorrhage
Singh, N., Moody, A. R., Zhang, B., Kaminski, I., Kapur, K., Chiu, S., & Tyrrell, P. N. (2017) · Stroke · doi:10.1161/strokeaha.117.017877 · Cited by 33
Targeting estrogen receptor signaling for treating heart failure
Qian, C., Liu, J.-J., & Liu, H.-D. (2023) · Heart Failure Reviews · doi:10.1007/s10741-023-10356-9 · Cited by 30
“Hodis et al. [62] discovered that the effects of estradiol (with or without progesterone) on the development of atherosclerosis varied depending on the timing of therapy initiation, with benefit noted when it was started in women who were less than 6 years past menopause but not in those who were…”
Background
Estradiol Treatment Initiated Early After Ovariectomy Regulates Myocardial Gene Expression and Inhibits Diastolic Dysfunction in Female Cynomolgus Monkeys: Potential Roles for Calcium Homeostasis and Extracellular Matrix Remodeling
Michalson, K. T., Groban, L., Howard, T. D., Shively, C. A., Sophonsritsuk, A., Appt, S. E., Cline, J. M., Clarkson, T. B., Carr, J. J., Kitzman, D. W., et al. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.009769 · Cited by 31
The vascular protective role of oestradiol: a focus on postmenopausal oestradiol deficiency and aneurysmal subarachnoid haemorrhage
Ramesh, S. S., Christopher, R., Devi, B. I., & Bhat, D. I. (2019) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12541 · Cited by 34
Predominance of Heart Failure With Preserved Ejection Fraction in Postmenopausal Women: Intra- and Extra-Cardiomyocyte Maladaptive Alterations Scaffolded by Estrogen Deficiency
Adekunle, A. O., Adzika, G. K., Mprah, R., Noah, M. L. N., Adu‐Amankwaah, J., Rizvi, R., Akhter, N., & Sun, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.685996 · Cited by 32
Sex Differences in Dementia
Hogervorst, E., Temple, S., & O’Donnell, E. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2022_408 · Cited by 35
Menopause and Aging
Løbo, R. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-47912-7.00014-7 · Cited by 33
Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause
Sriprasert, I., Hodis, H. N., Karim, R., Stanczyk, F. Z., Shoupe, D., Henderson, V. W., & Mack, W. J. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01600 · Cited by 32

Authors: Hodis, H. N., Mack, W. J., Henderson, V. W., Shoupe, D., Budoff, M. J., Hwang-Levine, J., Li, Y., Feng, M., Dustin, L., Kono, N., Stanczyk, F. Z., Selzer, R. H., & Azen, S. P.
Affiliations: General Department of Preventive Medicine (VN)
Stanford University (US)
University of California, Los Angeles (US)
ORCID: Mack, Wendy J.
Henderson, Victor W.
Budoff, Matthew J.
Li, Yanjie
Stanczyk, Frank Z.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2016-03-31
Volume: 374
Issue: 13
Pages: 1221-1231
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1505241
PMC: PMC4921205
OpenAlex: W2330799317
Cited by: 779
References: 42
Citations by year: 2026: 95 · 2025: 67 · 2024: 54 · 2023: 72 · 2022: 80 · 2021: 83 · 2020: 65 · 2019: 77 · 2018: 73 · 2017: 74 · 2016: 36
FWCI: 86.77
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institute on Aging (R01-AG024154-S2, R01AG-024154-01-05, R01AG024154, R01AG-024154-06-08)
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 › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords: hormone replacement therapy, estradiol, timing of hormone therapy initiation, carotid intima-media thickness, subclinical atherosclerosis, coronary artery calcium, coronary artery stenosis, coronary plaque, cardiovascular risk, menopause, progesterone, oral estradiol, cardiac CT, cardiovascular disease prevention, postmenopausal women
MeSH terms: Administration, Intravaginal, Administration, Oral, Carotid Arteries, Coronary Artery Disease, Drug Administration Schedule, Estradiol, Female, Humans, Middle Aged, Progesterone, Estrogen Replacement Therapy, Linear Models, Postmenopause, Disease Progression, Atherosclerosis, Carotid Intima-Media Thickness

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

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks