{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:35:11Z","timestamp":1792802111244,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also stimulates the endometrium and thus may increase the risk of endometrial cancer (EC). Materials and Methods: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled and uncontrolled clinical trials reporting on the prevalence and\/or incidence of EC among women using MHT. Results: 31 publications reporting on 21,306 women with EC diagnosed during or after MHT were identified. A significantly reduced risk of EC among continuous-combined (cc)MHT users with synthetic progestins (SPs) was demonstrated in 10\/19 studies with odds ratios (ORs)\/hazard ratios (HRs) between 0.24 and 0.71. Only one study documented an increased risk of EC among long-term users (\u226510 years), not confirmed in three other sub-group analyses of women with \u22656, \u22655, and &gt;10 years of ccMHT use. A significantly increased risk of EC among users of sequential-combined (sc)MHT with SPs was demonstrated in 6\/12 studies with ORs\/HRs between 1.38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc\/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9\/12 studies with ORs\/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women. Conclusion: ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc\/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.<\/jats:p>","DOI":"10.3390\/cancers12082195","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T09:41:21Z","timestamp":1596706881000},"page":"2195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6904-3258","authenticated-orcid":false,"given":"Clemens B.","family":"Tempfer","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Ruhr-Universit\u00e4t Bochum, Bochum, Germany and Comprehensive Cancer Center of the Ruhr-Universit\u00e4t Bochum (RUCCC), 44708 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad","family":"Hilal","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Ruhr-Universit\u00e4t Bochum, Bochum, Germany and Comprehensive Cancer Center of the Ruhr-Universit\u00e4t Bochum (RUCCC), 44708 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kern","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, St. Elisabeth-Krankenhaus Bochum, 44787 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingolf","family":"Juhasz-Boess","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University of Freiburg, 79110 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0852-6002","authenticated-orcid":false,"given":"G\u00fcnther A.","family":"Rezniczek","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Ruhr-Universit\u00e4t Bochum, Bochum, Germany and Comprehensive Cancer Center of the Ruhr-Universit\u00e4t Bochum (RUCCC), 44708 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/GCO.0000000000000338","article-title":"Treatment strategies for endometrial cancer: Current practice and perspective","volume":"29","author":"Lee","year":"2017","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1002\/ijc.31961","article-title":"Risk factors for endometrial cancer: An umbrella review of the literature","volume":"145","author":"Raglan","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_3","unstructured":"(2020, June 23). Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom, Langversion 1.0. AWMF Registernummer: 032\/034-OL. Available online: http:\/\/www.leitlinienprogramm-onkologie.de\/leitlinien\/endometriumkarzinom\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1210\/me.2010-0458","article-title":"Ligand-dependent degradation of SRC-1 is pivotal for progesterone receptor transcriptional activity","volume":"25","author":"Amazit","year":"2011","journal-title":"Mol. Endocrinol."},{"key":"ref_5","unstructured":"Wilson, J., Foster, D., and Kronenberg, H. (1998). Mechanisms of action of hormones that act as transcription-regulatory factors. Williams Textbook of Endocrinology, W.B. Saunders Company."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chlebowski, R.T., Anderson, G.L., Sarto, G.E., Haque, R., Runowicz, C.D., Aragaki, A.K., Thomson, C.A., Howard, B.V., Wactawski-Wende, J., and Chen, C. (2016). Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women\u2019s Health Initiative Randomized Trial. J. Natl. Cancer Inst., 108.","DOI":"10.1093\/jnci\/djv350"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1158\/1055-9965.EPI-09-0712","article-title":"Long-term postmenopausal hormone therapy and endometrial cancer","volume":"19","author":"Razavi","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/aje\/kwu146","article-title":"Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992\u20132008","volume":"180","author":"Fournier","year":"2014","journal-title":"Am. J. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1089\/jwh.2018.6956","article-title":"Increased Incidence of Endometrial Cancer Following the Women\u2019s Health Initiative: An Assessment of Risk Factors","volume":"28","author":"Constantine","year":"2019","journal-title":"J. Womens Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s10552-019-01233-8","article-title":"Circulating estrogens and postmenopausal ovarian and endometrial cancer risk among current hormone users in the Women\u2019s Health Initiative Observational Study","volume":"30","author":"Trabert","year":"2019","journal-title":"Cancer Causes Control"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1158\/1055-9965.EPI-17-0722","article-title":"Exogenous Hormone Use and Endometrial Cancer in U.S. Black Women","volume":"27","author":"Sponholtz","year":"2018","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/ijc.29878","article-title":"The influence of hormone therapies on type I and II endometrial cancer: A nationwide cohort study","volume":"138","author":"Kjaer","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.maturitas.2016.05.013","article-title":"Hormone replacement therapy and the risk of endometrial cancer: A systematic review","volume":"91","year":"2016","journal-title":"Maturitas"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s10552-015-0598-0","article-title":"Menopausal hormone therapy and mortality among endometrial cancer patients in the NIH-AARP Diet and Health Study","volume":"26","author":"Felix","year":"2015","journal-title":"Cancer Causes Control"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jsbmb.2013.05.001","article-title":"Menopausal hormone therapy and risk of endometrial cancer","volume":"142","author":"Brinton","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/ijc.27623","article-title":"Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk?","volume":"132","author":"Trabert","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.canep.2013.03.008","article-title":"Recent changes in endometrial cancer trends among menopausal-age U.S. women","volume":"37","author":"Wartko","year":"2013","journal-title":"Cancer Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1002\/ijc.26163","article-title":"Variations in sex hormone metabolism genes, postmenopausal hormone therapy and risk of endometrial cancer","volume":"130","author":"Razavi","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1002\/ijc.25762","article-title":"Endometrial cancer associated with various forms of postmenopausal hormone therapy: A case control study","volume":"128","author":"Jaakkola","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1007\/s10552-011-9840-6","article-title":"Long-term use of continuous-combined estrogen-progestin hormone therapy and risk of endometrial cancer","volume":"22","author":"Phipps","year":"2011","journal-title":"Cancer Causes Control"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1093\/aje\/kwq300","article-title":"Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition","volume":"172","author":"Allen","year":"2010","journal-title":"Am. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1158\/1055-9965.EPI-10-0832","article-title":"Body mass index, hormone replacement therapy, and endometrial cancer risk: A meta-analysis","volume":"19","author":"Crosbie","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1016\/j.ejca.2009.05.012","article-title":"The influence of menopausal hormone therapy on tumour characteristics and survival in endometrial cancer patients","volume":"45","author":"Hall","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1158\/1055-9965.EPI-07-2567","article-title":"Body mass and endometrial cancer risk by hormone replacement therapy and cancer subtype","volume":"17","author":"McCullough","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1158\/1055-9965.EPI-06-0675","article-title":"Lifetime weight history and endometrial cancer risk by type of menopausal hormone use in the NIH-AARP diet and health study","volume":"16","author":"Chang","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"139.e1","DOI":"10.1016\/j.ajog.2007.01.019","article-title":"Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer","volume":"197","author":"Doherty","year":"2007","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/cncr.22525","article-title":"Endometrial cancer and menopausal hormone therapy in the National Institutes of Health-AARP Diet and Health Study cohort","volume":"109","author":"Lacey","year":"2007","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1080\/13697130600953661","article-title":"Endometrial safety, overall safety and tolerability of transdermal continuous combined hormone replacement therapy over 96 weeks: A randomized open-label study","volume":"9","author":"Samsioe","year":"2006","journal-title":"Climacteric"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/aje\/kwj316","article-title":"Case-control study of postmenopausal hormone replacement therapy and endometrial cancer","volume":"164","author":"Strom","year":"2006","journal-title":"Am. J. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/S0140-6736(05)66455-0","article-title":"Endometrial cancer and hormone-replacement therapy in the Million Women Study","volume":"365","author":"Beral","year":"2005","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ejogrb.2005.02.018","article-title":"Hormone replacement therapy (HRT) and endometrial morphology under consideration of the different molecular pathways in endometrial carcinogenesis","volume":"122","author":"Horn","year":"2005","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/ijc.20389","article-title":"Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study","volume":"112","author":"Bakken","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.ajog.2004.04.041","article-title":"Dose of progestin in postmenopausal-combined hormone therapy and risk of endometrial cancer","volume":"191","author":"Reed","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_34","first-page":"848","article-title":"Risk of endometrial cancer and estrogen replacement therapy history by CYP17 genotype","volume":"61","author":"Feigelson","year":"2001","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0895-4356(99)00192-4","article-title":"Hormone replacement therapy and endometrial cancer in Ontario, Canada","volume":"53","author":"Jain","year":"2000","journal-title":"J. Clin. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1067\/mob.2000.108081","article-title":"Continuous combined hormone replacement therapy and risk of endometrial cancer","volume":"183","author":"Hill","year":"2000","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1001\/jama.1996.03530290040035","article-title":"Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen\/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial","volume":"275","author":"Judd","year":"1996","journal-title":"JAMA"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/8\/2195\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:57:04Z","timestamp":1760176624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/8\/2195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,6]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["cancers12082195"],"URL":"https:\/\/doi.org\/10.3390\/cancers12082195","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,6]]}}}