{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T21:25:24Z","timestamp":1787261124940,"version":"build-2736575974"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":217,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Does postmenopausal hormone replacement therapy (HRT), initiated within 1\u00a0year after menopause diagnosis, confer differential long-term health effects according to age at menopause?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Long-term postmenopausal HRT was associated with age-dependent clinical outcomes, with broadly consistent cardiovascular and skeletal associations across age groups, but more variable metabolic and oncological associations according to age at menopause.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>The \u2018timing hypothesis\u2019 suggests that HRT initiated closer to menopause may have more favorable cardiometabolic associations than later initiation, but evidence across distinct age-at-menopause strata remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This retrospective new-user cohort study utilized de-identified data from the TriNetX Research Network, which provided access to electronic medical records for \u223c111 million patients globally. To establish a relatively healthy baseline cohort, we included women aged 30\u201390\u2009years without prior major systemic diseases who had a documented diagnosis of menopause. To ensure adequate time for the development of hard clinical endpoints, we required that the index event (initial menopause diagnosis) occurred at least 10\u2009years before data extraction (31 December 2025), thereby guaranteeing a minimum follow-up period of one decade. To reduce immortal time bias and survivor bias inherent in prevalent-user designs, we employed a new-user, time-to-event cohort design. Women with a pre-existing history of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), osteoporosis, compression fracture, venous thromboembolism (VTE), breast cancer, or colorectal cancer on or before the index date were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Women who initiated postmenopausal HRT containing estrogen and\/or progestogen within 1\u00a0year after menopause diagnosis were propensity score-matched 1:1 with non-users using baseline demographic, clinical, and laboratory covariates. Primary matching yielded 83\u00a0670 matched pairs in women who experienced menopause at age \u226460\u2009years and 12\u00a0175 matched pairs in women who experienced menopause at age &amp;gt;60\u2009years. Time-to-event analyses using Cox proportional hazards regression were conducted across four clinically defined menopausal age strata: premature ovarian insufficiency (POI, &amp;lt;40\u2009years), early menopause (40\u201345\u2009years), normal menopause (46\u201360\u2009years), and late menopause (&amp;gt;60\u2009years). Hazard ratios (HRs) were calculated for incident T2DM, CVD, compression fracture, breast cancer, colorectal cancer, and VTE. Interaction P-values were calculated using the normal menopause group (46\u201360\u2009years) as the reference for interaction testing. Sensitivity analyses were conducted in both the overall \u226460-year and &amp;gt;60-year cohorts using an alternative 1:1 matching strategy based only on age, race, and baseline BMI, excluding laboratory parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>In the overall matched cohort of women experiencing menopause at age \u226460\u2009years, postmenopausal HRT was associated with lower hazards across all evaluated systemic endpoints. Compared with non-users, postmenopausal HRT was associated with lower hazards of T2DM (events: 3517 vs 4580; crude incidence: 4.20% vs 5.47%; HR: 0.595, 95% CI: 0.575\u20130.615) and CVD (events: 3960 vs 4413; crude incidence: 4.74% vs 5.29%; HR: 0.699, 95% CI: 0.688\u20130.709). Skeletal health was preserved, evidenced by a lower hazard of compression fractures (events: 426 vs 441; crude incidence: 0.51% vs 0.53%; HR: 0.780, 95% CI: 0.719\u20130.846). Furthermore, postmenopausal HRT was associated with lower hazards of breast cancer (events: 1281 vs 1504; crude incidence: 1.53% vs 1.80%; HR: 0.786, 95% CI: 0.743\u20130.831), colorectal cancer (events: 222 vs 276; crude incidence: 0.27% vs 0.33%; HR: 0.847, 95% CI: 0.738\u20130.971), and VTE (events: 1247 vs 1346; crude incidence: 1.49% vs 1.61%; HR: 0.859, 95% CI: 0.811\u20130.910). In the primary age-stratified model, the &amp;gt;60-year cohort showed a higher breast cancer hazard (HR: 1.151, 95% CI: 1.057\u20131.255); in the corresponding &amp;gt;60-year group sensitivity analysis, using alternative matching, the estimate remained directionally similar (HR: 1.218, 95% CI: 1.027\u20131.444). Across the remaining &amp;gt;60-year sensitivity outcomes, the direction of association was preserved, including continued lower hazards of T2DM, CVD, VTE, and compression fracture, while the colorectal cancer association remained neutral.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>Important limitations include residual confounding, incomplete socioeconomic and screening data, limited details on HRT formulation, route, dose and duration, unavailable breast cancer subtype information, unavailable exact maximum follow-up duration, and the inability to directly incorporate standardized patient-level geography into the matching or regression models. Region-restricted inference was additionally constrained because the Europe, Middle East, and Africa (EMEA)\u2009&amp;gt;\u200960-year HRT cohort contained only 48 exposed users, precluding stable matched analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>While cardiovascular and skeletal associations appeared broadly consistent across menopausal ages, the associations with breast cancer in the older age group highlight the critical need for individualized prescribing. These real-world findings are most consistent with earlier initiation of postmenopausal HRT for symptomatic women and those with POI, while urging extreme caution with initiation in late-onset menopause.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>No specific external funding was received. The study was supported by departmental funds from the Department of Obstetrics and Gynecology, Taichung Veterans General Hospital.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCLOSURES<\/jats:title>\n                    <jats:p>The authors declare no competing interests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/hropen\/hoag072","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:49:57Z","timestamp":1786016997000},"source":"Crossref","is-referenced-by-count":0,"title":["Long-term systemic outcomes of postmenopausal hormone replacement therapy by age at menopause: a real-world cohort study"],"prefix":"10.1093","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1338-5614","authenticated-orcid":false,"given":"Ting-Fang","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]},{"name":"Institute of Medicine, Chung Shan Medical University , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hsing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]},{"name":"Institute of Biomedical Sciences, PhD Programme in Translational Medicine and the Rong-Hsing Research Centre for Translational Medicine, National Chung-Hsing University , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsiang","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]},{"name":"Department of Public Health, Chung Shan Medical University , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Ting","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Tien","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]},{"name":"Centre for General Education, Ling Tung University , Taichung,","place":["Taiwan"]},{"name":"School of Medicine, China Medical University , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Ku","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]},{"name":"Department of Animal Science and Biotechnology, Tung Hai University , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lou","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]},{"name":"Department of Food and Nutrition, Providence University , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheau-Feng","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology & Women\u2019s Health Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]},{"name":"Department of Palliative Care Unit, Taichung Veterans General Hospital , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8858-0916","authenticated-orcid":false,"given":"Tsung-Hsien","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University , Taichung,","place":["Taiwan"]},{"name":"Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital , Taichung,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2026082016481078200_hoag072-B1","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/ijc.32868","article-title":"Postmenopausal hormone replacement therapy and colorectal cancer risk by molecular subtypes and pathways","volume":"147","author":"Amitay","year":"2020","journal-title":"Int J Cancer"},{"key":"2026082016481078200_hoag072-B2","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1158\/1078-0432.CCR-13-0325","article-title":"Molecular pathways: estrogen pathway in colorectal cancer","volume":"19","author":"Barzi","year":"2013","journal-title":"Clin Cancer Res"},{"key":"2026082016481078200_hoag072-B3","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1097\/GME.0000000000002267","article-title":"\u2018Tis but a scratch: a critical review of the Women\u2019s Health Initiative evidence associating menopausal hormone therapy with the risk of breast cancer","volume":"30","author":"Bluming","year":"2023","journal-title":"Menopause"},{"key":"2026082016481078200_hoag072-B4","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1080\/13697137.2023.2184252","article-title":"Menopause and diabetes","volume":"26","author":"Cerdas P\u00e9rez","year":"2023","journal-title":"Climacteric"},{"key":"2026082016481078200_hoag072-B5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1001\/jama.2020.9482","article-title":"Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women\u2019s Health Initiative randomized clinical trials","volume":"324","author":"Chlebowski","year":"2020","journal-title":"Jama"},{"key":"2026082016481078200_hoag072-B6","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/S1470-2045(12)70425-4","article-title":"Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies","volume":"13","author":"Collaborative Group on Hormonal Factors in Breast Cancer","year":"2012","journal-title":"Lancet Oncol"},{"key":"2026082016481078200_hoag072-B7","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/S0140-6736(19)31709-X","article-title":"Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence","volume":"394","author":"Collaborative Group on Hormonal Factors in Breast Cancer","year":"2019","journal-title":"Lancet"},{"key":"2026082016481078200_hoag072-B8","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1001\/jama.2022.24140","article-title":"Management of menopausal symptoms: a review","volume":"329","author":"Crandall","year":"2023","journal-title":"Jama"},{"key":"2026082016481078200_hoag072-B9","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.ajpath.2021.05.011","article-title":"The role of estrogen in insulin resistance: a review of clinical and preclinical data","volume":"191","author":"De Paoli","year":"2021","journal-title":"Am J Pathol"},{"key":"2026082016481078200_hoag072-B10","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/S0140-6736(02)08827-X","article-title":"Treatment of postmenopausal osteoporosis","volume":"359","author":"Delmas","year":"2002","journal-title":"Lancet"},{"key":"2026082016481078200_hoag072-B11","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1210\/jc.2019-00221","article-title":"Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society Clinical Practice guideline","volume":"104","author":"Eastell","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082016481078200_hoag072-B12","doi-asserted-by":"crossref","first-page":"e506","DOI":"10.1161\/CIR.0000000000000912","article-title":"Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the American Heart Association","volume":"142","author":"El Khoudary","year":"2020","journal-title":"Circulation"},{"key":"2026082016481078200_hoag072-B13","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1001\/jama.2017.16952","article-title":"Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: evidence report and systematic review for the US Preventive Services Task Force","volume":"318","author":"Gartlehner","year":"2017","journal-title":"Jama"},{"key":"2026082016481078200_hoag072-B14","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1001\/jama.2022.18324","article-title":"Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: updated evidence report and systematic review for the US Preventive Services Task Force","volume":"328","author":"Gartlehner","year":"2022","journal-title":"Jama"},{"key":"2026082016481078200_hoag072-B15","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ogc.2011.05.002","article-title":"The timing of the age at which natural menopause occurs","volume":"38","author":"Gold","year":"2011","journal-title":"Obstet Gynecol Clin North Am"},{"key":"2026082016481078200_hoag072-B16","doi-asserted-by":"crossref","first-page":"101551","DOI":"10.1016\/j.beem.2021.101551","article-title":"Menopausal hormone therapy for the management of osteoporosis","volume":"35","author":"Gosset","year":"2021","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"2026082016481078200_hoag072-B17","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/13697130500042417","article-title":"KEEPS: the Kronos Early Estrogen Prevention Study","volume":"8","author":"Harman","year":"2005","journal-title":"Climacteric"},{"key":"2026082016481078200_hoag072-B18","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0140-6736(05)66519-1","article-title":"Treatment of menopausal symptoms: what shall we do now?","volume":"366","author":"Hickey","year":"2005","journal-title":"Lancet"},{"key":"2026082016481078200_hoag072-B19","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/PPO.0000000000000591","article-title":"Menopausal hormone replacement therapy and reduction of all-cause mortality and cardiovascular disease: it is about time and timing","volume":"28","author":"Hodis","year":"2022","journal-title":"Cancer J"},{"key":"2026082016481078200_hoag072-B20","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1056\/NEJMoa1505241","article-title":"Vascular effects of early versus late postmenopausal treatment with estradiol","volume":"374","author":"Hodis","year":"2016","journal-title":"N Engl J Med"},{"key":"2026082016481078200_hoag072-B21","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/GME.0000000000000343","article-title":"Methods and baseline cardiovascular data from the early versus late intervention trial with estradiol testing the menopausal hormone timing hypothesis","volume":"22","author":"Hodis","year":"2015","journal-title":"Menopause"},{"key":"2026082016481078200_hoag072-B22","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41574-022-00708-0","article-title":"The interplay between diabetes mellitus and menopause: clinical implications","volume":"18","author":"Lambrinoudaki","year":"2022","journal-title":"Nat Rev Endocrinol"},{"key":"2026082016481078200_hoag072-B23","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.jacc.2022.05.016","article-title":"Contributions of the Women\u2019s Health Initiative to cardiovascular research: JACC state-of-the-art review","volume":"80","author":"LaMonte","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"2026082016481078200_hoag072-B24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/13697137.2020.1851183","article-title":"Hormone replacement therapy \u2013 where are we now?","volume":"24","author":"Langer","year":"2021","journal-title":"Climacteric"},{"key":"2026082016481078200_hoag072-B25","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s00198-018-4414-z","article-title":"Estrogen therapy for osteoporosis in the modern era","volume":"29","author":"Levin","year":"2018","journal-title":"Osteoporos Int"},{"key":"2026082016481078200_hoag072-B26","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1158\/0008-5472.CAN-11-2619","article-title":"Postmenopausal hormone therapy is associated with a reduced risk of colorectal cancer lacking CDKN1A expression","volume":"72","author":"Lin","year":"2012","journal-title":"Cancer Res"},{"key":"2026082016481078200_hoag072-B27","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1007\/s00198-022-06483-y","article-title":"Menopausal hormone therapy reduces the risk of fracture regardless of falls risk or baseline FRAX probability-results from the Women\u2019s Health Initiative hormone therapy trials","volume":"33","author":"Lorentzon","year":"2022","journal-title":"Osteoporos Int"},{"key":"2026082016481078200_hoag072-B28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2217\/WHE.14.82","article-title":"Current concepts in premature ovarian insufficiency","volume":"11","author":"Maclaran","year":"2015","journal-title":"Womens Health (Lond)"},{"key":"2026082016481078200_hoag072-B29","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1210\/jcem.85.4.6530","article-title":"Effects of the menopause, gender, and estrogen replacement therapy on vascular nitric oxide activity","volume":"85","author":"Majmudar","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082016481078200_hoag072-B30","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1001\/jama.2024.6542","article-title":"The Women\u2019s Health Initiative randomized trials and clinical practice: a review","volume":"331","author":"Manson","year":"2024","journal-title":"Jama"},{"key":"2026082016481078200_hoag072-B31","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1056\/NEJM200107053450106","article-title":"Clinical practice. Postmenopausal hormone-replacement therapy","volume":"345","author":"Manson","year":"2001","journal-title":"N Engl J Med"},{"key":"2026082016481078200_hoag072-B32","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1210\/er.2012-1055","article-title":"The role of estrogens in control of energy balance and glucose homeostasis","volume":"34","author":"Mauvais-Jarvis","year":"2013","journal-title":"Endocr Rev"},{"key":"2026082016481078200_hoag072-B33","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1097\/GME.0000000000001326","article-title":"The Kronos Early Estrogen Prevention Study (KEEPS): what have we learned?","volume":"26","author":"Miller","year":"2019","journal-title":"Menopause"},{"key":"2026082016481078200_hoag072-B34","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/S0140-6736(23)02800-3","article-title":"Optimising health after early menopause","volume":"403","author":"Mishra","year":"2024","journal-title":"Lancet"},{"key":"2026082016481078200_hoag072-B35","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/cen.14469","article-title":"Impact of menopausal hormone therapy on colorectal cancer risk: a systematic review","volume":"95","author":"Nakhostin","year":"2021","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2026082016481078200_hoag072-B36","doi-asserted-by":"crossref","first-page":"4873","DOI":"10.1113\/JP278063","article-title":"Mechanisms underlying the influence of oestrogen on cardiovascular physiology in women","volume":"597","author":"Novella","year":"2019","journal-title":"J Physiol"},{"key":"2026082016481078200_hoag072-B37","first-page":"123","article-title":"A systematic review and meta-regression analysis to examine the \u2018timing hypothesis\u2019 of hormone replacement therapy on mortality, coronary heart disease, and stroke","volume":"22","author":"Nudy","year":"2019","journal-title":"Int J Cardiol Heart Vasc"},{"key":"2026082016481078200_hoag072-B38","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3109\/13697137.2016.1164408","article-title":"Hormone therapy and large bowel cancer revisited","volume":"19","author":"Pines","year":"2016","journal-title":"Climacteric"},{"key":"2026082016481078200_hoag072-B39","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1056\/NEJMcp1714787","article-title":"Hormone therapy for postmenopausal women","volume":"382","author":"Pinkerton","year":"2020","journal-title":"N Engl J Med"},{"key":"2026082016481078200_hoag072-B40","doi-asserted-by":"crossref","first-page":"4542","DOI":"10.1200\/JCO.2009.22.0764","article-title":"Use of hormone replacement therapy and the risk of colorectal cancer","volume":"27","author":"Rennert","year":"2009","journal-title":"J Clin Oncol"},{"key":"2026082016481078200_hoag072-B41","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1177\/2047487314556004","article-title":"Cardiovascular disease risk in women with premature ovarian insufficiency: a systematic review and meta-analysis","volume":"23","author":"Roeters van Lennep","year":"2016","journal-title":"Eur J Prev Cardiol"},{"key":"2026082016481078200_hoag072-B42","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1001\/jama.288.3.321","article-title":"Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women\u2019s Health Initiative randomized controlled trial","volume":"288","author":"Rossouw","year":"2002","journal-title":"Jama"},{"key":"2026082016481078200_hoag072-B43","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1158\/0008-5472.CAN-12-4051","article-title":"Colorectal cancer risk associated with hormone use varies by expression of estrogen receptor-\u03b2","volume":"73","author":"Rudolph","year":"2013","journal-title":"Cancer Res"},{"key":"2026082016481078200_hoag072-B44","doi-asserted-by":"crossref","first-page":"dgaa073","DOI":"10.1210\/clinem\/dgaa073","article-title":"Underlying breast cancer risk and menopausal hormone therapy","volume":"105","author":"Santen","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082016481078200_hoag072-B45","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1055\/s-0045-1810601","article-title":"The long-term health effects of early menopause","volume":"43","author":"Savukoski","year":"2025","journal-title":"Semin Reprod Med"},{"key":"2026082016481078200_hoag072-B46","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1001\/jama.2025.14187","article-title":"New analysis of Women\u2019s Health Initiative data aims to \u201cclear the air\u201d over menopausal hormone therapy","volume":"334","author":"Schweitzer","year":"2025","journal-title":"Jama"},{"key":"2026082016481078200_hoag072-B47","doi-asserted-by":"crossref","first-page":"H395","DOI":"10.1152\/ajpheart.00430.2018","article-title":"Aging women and their endothelium: probing the relative role of estrogen on vasodilator function","volume":"317","author":"Somani","year":"2019","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026082016481078200_hoag072-B48","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.2337\/dc23-0451","article-title":"Effect of postmenopausal hormone therapy on glucose regulation in women with type 1 or type 2 diabetes: a systematic review and meta-analysis","volume":"46","author":"Speksnijder","year":"2023","journal-title":"Diabetes Care"},{"key":"2026082016481078200_hoag072-B50","doi-asserted-by":"crossref","first-page":"1617731","DOI":"10.3389\/fendo.2025.1617731","article-title":"Chapter 3. Impact of estrogens on hemostasis","volume":"16","author":"Stanczyk","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026082016481078200_hoag072-B51","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1056\/NEJMcp2116488","article-title":"Primary ovarian insufficiency","volume":"388","author":"Stuenkel","year":"2023","journal-title":"N Engl J Med"},{"key":"2026082016481078200_hoag072-B52","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ejca.2017.06.013","article-title":"Association of the oestrogen receptor beta with hormone status and prognosis in a cohort of female patients with colorectal cancer","volume":"83","author":"Topi","year":"2017","journal-title":"Eur J Cancer"},{"key":"2026082016481078200_hoag072-B53","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1001\/jama.2022.18625","article-title":"Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: US Preventive Services Task Force recommendation statement","volume":"328","author":"US Preventive Services Task Force","year":"2022","journal-title":"Jama"},{"key":"2026082016481078200_hoag072-B54","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2337\/db18-0638","article-title":"Estrogen improves insulin sensitivity and suppresses gluconeogenesis via the transcription factor Foxo1","volume":"68","author":"Yan","year":"2019","journal-title":"Diabetes"},{"key":"2026082016481078200_hoag072-B55","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1097\/GME.0000000000002376","article-title":"Relationship between menopausal hormone therapy and colorectal cancer: a cohort study utilizing the health insurance database in South Korea (HISK)-II","volume":"31","author":"Yuk","year":"2024","journal-title":"Menopause"}],"container-title":["Human Reproduction Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hropen\/advance-article-pdf\/doi\/10.1093\/hropen\/hoag072\/70510308\/hoag072.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hropen\/article-pdf\/2026\/3\/hoag072\/70510308\/hoag072.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hropen\/article-pdf\/2026\/3\/hoag072\/70510308\/hoag072.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T20:48:27Z","timestamp":1787258907000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hropen\/article\/doi\/10.1093\/hropen\/hoag072\/8753570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5,19]]}},"URL":"https:\/\/doi.org\/10.1093\/hropen\/hoag072","relation":{},"ISSN":["2399-3529"],"issn-type":[{"value":"2399-3529","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"hoag072"}}