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

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Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

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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

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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.).

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Background
17β-estradiol lowers triglycerides in adipocytes via estrogen receptor α and it may be attenuated by inflammation
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“Estradiol also has a certain protective effect on cardiovascular diseases [66, 67].”
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'Tis but a scratch: a critical review of the Women's Health Initiative evidence associating menopausal hormone therapy with the risk of breast cancer
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“In this issue of the Journal , Hodis et al. 6 provide a test of this hypothesis in the Early versus Late Intervention Trial with Estradiol (ELITE).”
Background
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“In older women of Estrogen Early versus Late Intervention with Estadiol (ELITE), estrogen treatments reduced the rate of increase of carotid intima-medial thickness (Hodis et al., 2016), a result consistent with the finding of this study that estrogen lowered the endothelial-prominent GDF15 SASP.”
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“In the ELITE trial, in 643 women there was one case of MI in the early postmenopausal group (n¼ 1 placebo, n¼ 0 MHT) and three cases in the late postmenopausal group (n¼ 2 placebo, n¼ 1 MHT), one case of transient ischemic attack in the early postmenopausal group (n¼ 1 placebo, n¼ 0 MHT) and two cases in the late post…”
BackgroundMethodInfluential
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Sex hormones, vascular factors and cognition
Szoeke, C. E. I., Downie, S., Parker, A. F., & Phillips, S. (2021) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100927 · Cited by 26
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Background
Estradiol mediates colonic epithelial protection in aged mice after stroke and is associated with shifts in the gut microbiome
Lee, J., Peesh, P., Quaicoe, V. A., Tan, C., Banerjee, A., Mooz, P., Ganesh, B. P., Petrosino, J. F., Bryan, R. M., McCullough, L. D., et al. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2271629 · Cited by 28
“…control studies, including the Kronos Early Estrogen and Prevention Study (KEEPs) and Early versus Late Intervention Trial with Estradiol (ELITE), 27 demonstrate that the risk of adverse cardiovascular events for HT is low for women 60 y of age or within 10 y from menopause, showing the…”
Background
Apolipoprotein E4 genotype in combination with poor metabolic profile is associated with reduced cognitive performance in healthy postmenopausal women: implications for late onset Alzheimer's disease
Karim, R., Koç, M., Rettberg, J. R., Hodis, H. N., Henderson, V. W., John, J. A. S., Allayee, H., Brinton, R. D., & Mack, W. J. (2018) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001160 · Cited by 24
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“Hormone replacement therapy (HT), if started in early menopause, has been suggested to be beneficial for CV health by decreasing both carotid artery intima-media thickness and blood pressure (28), but evidence regarding PWV and AIx have remained inconclusive.”
Background
Neuronal GPER Participates in Genistein-Mediated Neuroprotection in Ischemic Stroke by Inhibiting NLRP3 Inflammasome Activation in Ovariectomized Female Mice
Wang, S., Zhang, Z., Wang, J., Ma, L., Zhao, J., Wang, J., Fang, Z., Hou, W., & Guo, H. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02894-4 · Cited by 25
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“The Early versus Late Intervention with Estrogen (ELITE) trial reported that early intervention is the key to success of HRT because initiation of HRT 10 years after menopause did not show any benefit in reducing risk of atherosclerotic vascular disease (Hodis et al. 2016).”
Background
The synergistic effects of vitamin D and estradiol deficiency on metabolic syndrome in Chinese postmenopausal women
Huang, H., Guo, J., Chen, Q., Chen, X., Yang, Y., Zhang, W., Liu, Y., Chen, X., & Yang, D. (2019) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001370 · Cited by 25
A single dose of estrogen during hemorrhagic shock protects against Kidney Injury whereas estrogen restoration in ovariectomized mice is ineffective
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“Although cIMT progression was slower in the estradiol group, the clinical significance of this was unclear as events were too few to detect differences between randomization arms [3].”
BackgroundInfluential
Effect of menopausal hormone therapy on arterial wall echomorphology: Results from the Early versus Late Intervention Trial with Estradiol (ELITE)
Karim, R., Xu, W., Kono, N., Sriprasert, I., Li, Y., Yan, M., Stanczyk, F. Z., Shoupe, D., Mack, W. J., & Hodis, H. N. (2022) · Maturitas · doi:10.1016/j.maturitas.2022.02.007 · Cited by 24
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“Indeed, data from the Early versus Late Estrogen Trial demonstrated that while women who were 10 years past menopause experience no coronary benefit from hormone therapy, women who were less than 6 years past menopause has less progression of subclinical atherosclerosis (269).”
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“Moreover, MHT has been shown to protect against global ischaemia-induced neuronal cell death and reduced carotid artery intima-media thickness in early menopause but not late menopause 86 .”
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“events and a widely used surrogate measure for intervention studies.(17,18) Plaque is a direct measure of atherosclerosis, and its presence in the carotid arteries may better predict CVD risk compared with CIMT alone.”
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Gersh, F. L., O’Keefe, J. H., & Lavie, C. J. (2021) · Heart · doi:10.1136/heartjnl-2019-316323 · Cited by 23
Phytoestrogen-Rich Natural Preparation for Treatment of Climacteric Syndrome and Atherosclerosis Prevention in Perimenopausal Women
Kirichenko, T. V., Myasoedova, V. A., Orekhova, V. A., Ravani, A. L., Никитина, Н. А., Grechko, A. V., Sobenin, I. A., & Orekhov, A. N. (2017) · Phytotherapy Research · doi:10.1002/ptr.5841 · Cited by 23
“Hodis and colleagues have shown the antiatherosclerotic effect of HT on c-IMT progression in women with early postmenopause but not late postmenopause (Hodis et al., 2016).”
Background
Evidence on the use of progesterone in menopausal hormone therapy
Mirkin, S. (2018) · Climacteric · doi:10.1080/13697137.2018.1455657 · Cited by 23
How Does Mental Health Impact Women's Heart Health?
O'Neil, A. E., Russell, J. D., & Murphy, B. M. (2020) · Heart Lung and Circulation · doi:10.1016/j.hlc.2020.05.111 · Cited by 23
Sexual dimorphism in cardiac remodeling: the molecular mechanisms ruled by sex hormones in the heart
Ferreira, C., Trindade, F., Ferreira, R. M., Neves, J. S., Leite-Moreira, A. F., Amado, F. M. L., Santos, M., & Nogueira‐Ferreira, R. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02169-w · Cited by 23
“Besides, the start of HRT early after menopause significantly decreases the risk of mortality, myocardial infarction, or HF [28, 31].”
Background
Applications of Calcium-Based Nanomaterials in Osteoporosis Treatment
Deng, Y., Wei, W., & Tang, P. (2022) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c01306 · Cited by 23
The Current Strategy in Hormonal and Non-Hormonal Therapies in Menopause—A Comprehensive Review
Pop, A. L., Năsui, B. A., Roxana Georgiana, B. O. R. S., Peneş, O. N., Prada, A. G., Cloțea, E., Crisan, S., Cobelschi, C., Mehedințu, C., Cârstoiu, M., et al. (2023) · Life · doi:10.3390/life13030649 · Cited by 26
“In addition, atherosclerosis deposits evaluated by cardiac CT did not vary significantly with estradiol therapy in both menopause groups [41].”
Background
Understanding of and clinical approach to cardiometabolic transition at the menopause
Lambrinoudaki, I. V., & Armeni, E. (2023) · Climacteric · doi:10.1080/13697137.2023.2202809 · Cited by 24
“The ELITE trial (Effects of Early versus Late Postmenopausal Treatment with Estradiol) included 643 postmenopausal women who were randomized to 1 mg estradiol (combined with or without vaginal progesterone) versus placebo and were followed up for up to 5 years [67,68].”
MethodResult
Novel effects of phytoestrogenic soy isoflavones on serum calcium and chloride in premenopausal women: A 2-year double-blind, randomized, placebo-controlled study
Lu, L. W., Chen, N., Nayeem, F., Ramanujam, V. M. S., Kuo, Y., Brunder, D. G., Nagamani, M., & Anderson, K. E. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2017.11.002 · Cited by 22
“We chose to study premenopausal women because soy is usually consumed lifelong by populations accustomed to legumes as staple food sources, and there is evidence that earlier initiation of hormone replacements may lead to better health outcomes [30, 31].”
Background
Increased cardiac and stroke death risk in the first year after discontinuation of postmenopausal hormone therapy
Venetkoski, M., Savolainen-Peltonen, H. M., Rahkola‐Soisalo, P., Hoti, F. J., Vattulainen, P., Gissler, M., Ylikorkala, O., & Mikkola, T. S. (2017) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001023 · Cited by 22
“Increasing evidence suggests that shorter periods between the onset of menopause and the initiation of HT are associated with stronger protection against cardiovascular disease.(3,4) In the Women’s Health Initiative clinical trial, the use of conjugated equine estrogen”
Background
Traditional and Emerging Sex-Specific Risk Factors for Cardiovascular Disease in Women
Mehta, P. K., Gaignard, S. M., Schwartz, A. M., & Manson, J. E. (2022) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2308288 · Cited by 23
“…tested the timing hypothesis, found that oral estradiol (1 mg/day), with or without progesterone vaginal gel, was associated with less progression of carotid-intima media thickness (CIMT) at a 5-year median follow-up if initiated early (within 6 years postmenopause) compared to placebo [113].”
BackgroundInfluential
Qixian granule inhibits ferroptosis in vascular endothelial cells by modulating TRPML1 in the lysosome to prevent postmenopausal atherosclerosis
Zhang, M., Mao, C., Dai, Y., Xu, X., & Wang, X. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.118076 · Cited by 21
Stroke in Women
Christensen, H., & Bushnell, C. (2020) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000836 · Cited by 23
Progestogen safety and tolerance in hormonal replacement therapy
Palacios, S., & Mejía, A. (2016) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2016.1223041 · Cited by 21
Associations between hip bone mineral density, aortic calcification and cardiac workload in community-dwelling older Australians
Rodríguez, A. J., Scott, D. S., Hodge, A. M., English, D. R., Giles, G. G., & Ebeling, P. R. (2017) · Osteoporosis International · doi:10.1007/s00198-017-4024-1 · Cited by 21
“Estradiol therapy in a randomised trial was successful in reducing subclinical atherosclerosis, suggesting a direct role for oestrogen-containing hormones in cardiovascular disease in older females [20].”
Background
Emerging Research on the Implications of Hormone Replacement Therapy on Coronary Heart Disease
Keck, C., & Taylor, M. H. (2018) · Current Atherosclerosis Reports · doi:10.1007/s11883-018-0758-2 · Cited by 21
Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus?
Yassine, H. N., Anderson, A., Brinton, R. D., Carmichael, O. T., Espeland, M. A., Hoscheidt, S. M., Hugenschmidt, C. E., Keller, J. N., Peters, A. L., & Pi-Sunyer, X. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.03.020 · Cited by 22
Postmenopausal Hormone Therapy—Local and Systemic: A Pharmacologic Perspective
Smith, T. L., Sahni, S., & Thacker, H. L. (2020) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1740 · Cited by 21
Effects of aging and endurance exercise training on cardiorespiratory fitness and cardiac structure and function in healthy midlife and older women
Carrick‐Ranson, G., Howden, E. J., Brazile, T. L., Levine, B. D., & Reading, S. A. (2023) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00798.2022 · Cited by 20
Reproductive milestones across the lifespan and cardiovascular disease risk in women
Stuenkel, C. A. (2023) · Climacteric · doi:10.1080/13697137.2023.2259793 · Cited by 21
“After 5 years of follow-up, carotid intima-media thickness had not progressed to the same degree in the women who started estrogen <6 years since menopause; CAC was similar between treatment groups [92].”
Background
The role of sex hormones in aldosterone biosynthesis and their potential impact on its mineralocorticoid receptor
Vecchiola, A., Uslar, T., Friedrich, I., Aguirre, J., Sandoval, A., Carvajal, C. A., Tapia-Castillo, A., Martínez, A., & Fardella, C. (2024) · Cardiovascular Endocrinology & Metabolism · doi:10.1097/xce.0000000000000305 · Cited by 20
“The cessation of estrogen production in postmenopausal women leads to an increase in BP, and early estrogen replacement therapy could prevent this increase in BP and atherosclerotic progression [17,18].”
Background
A theory of eu-estrogenemia: a unifying concept
Turner, R. J., & Kerber, I. J. (2017) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000895 · Cited by 20
Guideline No. 422e: Menopause and Cardiovascular Disease
Abramson, B. L., Black, D., Christakis, M. K., Fortier, M. P., & Wolfman, W. (2021) · Journal of Obstetrics and Gynaecology Canada · doi:10.1016/j.jogc.2021.09.010 · Cited by 20
From sex hormone decrease to hormonal treatment: impacts on cardiovascular risk with ageing
Fontaine, C., Gosset, A., Davezac, M., Buscato, M., Grouthier, V., Renault, M., Henrion, D., Trémollières, F., Schumacher, M., Lenfant, F., et al. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf086 · Cited by 19
Menopausal Hormone Therapy—Risks, Benefits and Emerging Options: A Narrative Review
Arnautu, A. M., Nimigean, V. R., Nacea, C. A., Tilici, D.-M., & Păun, D. L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262211098 · Cited by 19
“In particular, studies such as ELITE and KEEPS suggested a more favorable vascular profile when therapy is initiated closer to the menopause transition (“timing hypothesis”), while confirming symptomatic efficacy [3,4].”
Menopausal hormone therapy for women living with HIV
King, E. M., Prior, J. C., Pick, N., van Schalkwyk, J., Kestler, M., Tkachuk, S., Loutfy, M. R., & Murray, M. C. M. (2021) · The Lancet HIV · doi:10.1016/s2352-3018(21)00148-x · Cited by 18
The effects of estrogen and hormone replacement therapy on platelet activity: a review.
Hashemzadeh, M., Haseefa, F., Peyton, L., Park, S., & Movahed, M. R. (2022) · PubMed Central · Cited by 19
Menopausal hormone therapy and coronary heart disease: the roller-coaster history
Nudy, M. S., Buerger, J. D., Dreibelbis, S., Jiang, X., Hodis, H. N., & Schnatz, P. F. (2023) · Climacteric · doi:10.1080/13697137.2023.2282690 · Cited by 20
“There was no significant difference in women who initiated HT 10 years or more after menopause (median 14 years) [69].”
BackgroundInfluential
Effects of Short-Term Dried Plum (Prune) Intake on Markers of Bone Resorption and Vascular Function in Healthy Postmenopausal Women: A Randomized Crossover Trial
Al-Dashti, Y. A., Holt, R. R., Carson, J. G., Keen, C. L., & Hackman, R. M. (2019) · Journal of Medicinal Food · doi:10.1089/jmf.2018.0209 · Cited by 19
“62 Whether or not differential responses occur between ‘‘early versus late’’ menopause with dietary bioactives merits further study.”
The Effect of Perimenopausal Transdermal Estradiol and Micronized Progesterone on Markers of Risk for Arterial Disease
Gordon, J. L., Rubinow, D. R., Watkins, L. L., Hinderliter, A. L., Caughey, M. C., & Girdler, S. S. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz262 · Cited by 19
Menopausal hormone therapy and risk of incident hypertension: role of the route of estrogen administration and progestogens in the E3N cohort
Madika, A., MacDonald, C. J., Fournier, A., Mounier‐Véhier, C., Béraud, G., & Boutron‐Ruault, M. (2021) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001839 · Cited by 19
“Our results are in line with some previous studies.2,6,7,10,13 In a large Australian cohort of 43,405 women, the risk of hypertension was higher in current or past MHT users compared with never users.2 In the Women’s Health Initiative trial, the use of CEE administered orally, with or without medroxyprogesterone, was…”
Background
Menopause: A complex and controversial journey
Chalouhi, S. E. (2017) · Post Reproductive Health · doi:10.1177/2053369117711346 · Cited by 19
“On the other hand, and despite the feminist’s argument against HRT, its lucrative implication in the treatment of menopause and its potential risks (largely drawn from the women’s Health Initiative trial (WHI)), the latest research concerning HRT proves its relative safety and argues strongly against the WHI’s finding…”
Result
Quercetin alleviates postmenopausal atherosclerosis by suppressing endothelial cell ferroptosis via regulating the KEAP1/NRF2/GPX4 signalling pathway
Lv, Y., Weng, X., Zhu, Y., Zhang, X., Ma, Y., Dai, X., Bai, X., Zhang, S., Qi, J., Zhu, X., et al. (2025) · British Journal of Pharmacology · doi:10.1111/bph.70200 · Cited by 20
“However, findings from large-scale clinical trials indicate that the therapeutic efficacy of hormone replacement therapy (HRT) remains controversial, and its routine clinical use is still not recommended (Hodis et al., 2016).”
Role of reproductive and menopausal factors in functional and structural progression of rheumatoid arthritis: results from the SCQM cohort
Alpizar-Rodriguez, D., Förger, F., Courvoisier, D. S., Gabay, C., & Finckh, A. (2018) · Lara D. Veeken · doi:10.1093/rheumatology/key311 · Cited by 18
Estradiol‐17β inhibits homocysteine mediated damage by promoting H2S production via upregulating CBS and CSE expression in human umbilical vein endothelial cells
Zhang, D., Hong, X., Wang, J., Jiang, Y., Zhang, Y., Chen, J., & Niu, X. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29527 · Cited by 18
“In addition, epidemiology shows that women of reproductive age have a lower incidence of CV events than that of men at the same age, while the incidence of CV events in postmenopausal women is gradually dropping to be consistent with that of men.(18) Changes in female peri‐ menopausal estrogen are characterized by inc…”
Result
Subclinical carotid artery atherosclerosis and cognitive function in older adults
Lin, F., Pa, J., Karim, R., Hodis, H. N., Han, S. D., Henderson, V. W., John, J. A. S., & Mack, W. J. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-00997-7 · Cited by 18
“1 mm, the approximate standard deviation from the study population [13, 28, 29].”
Background
Relationships between endogenous and exogenous testosterone and cardiovascular disease in men
Thirumalai, A., & Anawalt, B. D. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-022-09752-7 · Cited by 20
A multi-tissue transcriptomic landscape of female mice in estrus and diestrus provides clues for precision medicine
Zhou, Y., Yan, H., Liu, W., Hu, C., Zhou, Y., Sun, R., Tang, Y., Zheng, C., Yang, J., & Cui, Q. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.983712 · Cited by 19
“So far, some researches have revealed the efficiency of HT in preventing cardiovascular diseases in early menopausal women (Barrett-Connor and Bush, 1991; Hodis et al., 2016), but there are also researches reporting neutral effects (Hulley et al.”
Background
National Institute on Aging 's 50th anniversary: Advancing aging research and the health and well‐being of older adults
Kelley, A. S., Addie, S., Carrington‐Lawrence, S., Ferrucci, L., Jones, P., Hadley, E., Haim, T., Harper, J., Kahana, S. Y., Kelley, M. S., et al. (2024) · Journal of the American Geriatrics Society · doi:10.1111/jgs.18837 · Cited by 18
“21 • Deprescribing .”
Risks and benefits of hormone therapy after menopause for cognitive decline and dementia: A conceptual review
Rocca, W. A., Kantarci, K., & Faubion, S. S. (2024) · Maturitas · doi:10.1016/j.maturitas.2024.108003 · Cited by 18
Use of cardiovascular age for assessing risks and benefits of menopausal hormone therapy
Santen, R. J. (2017) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000847 · Cited by 18
Sex and ethnic differences in the cardiovascular complications of type 2 diabetes
Yeo, J. L., Brady, E. M., McCann, G. P., & Gulsin, G. S. (2021) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188211034297 · Cited by 19
Clinical trials in menopause
Marko, K. I., & Simon, J. A. (2017) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000978 · Cited by 18
Influence of menopausal hormone therapy on body composition and metabolic parameters
Costa, G. B. C., Carneiro, G., Umeda, L., Pardini, D., & Zanella, M. T. (2020) · BioResearch Open Access · doi:10.1089/biores.2019.0050 · Cited by 17
“(measured as carotid artery intima-media thickness) than was placebo when therapy was initiated within 6 years after menopause.(7) These results are consistent with results of other studies that have suggested that the effects of HT on CVD may depend on the timing of therapy initiation relative to menopause.”
Result
Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability
Ansari, N. N., Spilioti, E., Kyrou, I., Kalotychou, V., Chatzigeorgiou, A., Sanoudou, D., Dahlman‐Wright, K., Randeva, H. S., Papavassiliou, A. G., Moutsatsou, P., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810960 · Cited by 17
“protective effects without adverse effects [83,84].”
BackgroundResult
Hypertension across a Woman's lifespan
D’Ignazio, T., Grand’Maison, S., Bérubé, L., Forcillo, J., & Pacheco, C. (2022) · Maturitas · doi:10.1016/j.maturitas.2022.11.006 · Cited by 19
Sex Hormones, the Stool Microbiome, and Subclinical Atherosclerosis in Women With and Without HIV
Peters, B. A., Hanna, D. B., Wang, Y., Weber, K. M., Topper, E. T., Appleton, A. A., Sharma, A., Hodis, H. N., Santoro, N. F., Guillemette, C., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad510 · Cited by 17
The impact of female sex hormones on cardiovascular disease: from mechanisms to hormone therapy
Kan, Y., Peng, Y., Zhao, Z.-H., Dong, S., Xu, Y.-X., Ma, X., Liu, X., Liu, Y., & Yu-Jie, Z. H. O. U. (2024) · 老年心脏病学杂志：英文版 · doi:10.26599/1671-5411.2024.06.003 · Cited by 25

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

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Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

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