{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T15:33:21Z","timestamp":1782228801248,"version":"3.54.5"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1175","license":[{"start":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T00:00:00Z","timestamp":1686441600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Observational studies have shown an association between age at menarche (AAM) and the risk of gynecological diseases. However, the causality cannot be determined due to residual confounding.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a Mendelian randomization (MR) study to evaluate the causal effect of AAM on several gynecological diseases, including endometriosis, female infertility, pre-eclampsia or eclampsia, uterine fibroids, breast cancer, ovarian cancer, and endometrial cancer. Single nucleotide polymorphisms were used as genetic instruments. The inverse variance weighted method was used as the primary approach and several other MR models were conducted for comparison. Cochran\u2019s Q test, Egger\u2019s intercept test, and leave-one-out analysis were conducted for sensitivity analysis. Radial MR analysis was conducted when detecting the existence of heterogeneity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>After Bonferroni correction and thorough sensitivity analysis, we observed a robust causal effect of AAM on endometrial cancer (odds ratio:\u00a00.80; 95% confidence interval:\u00a00.72\u20130.89; P\u2009=\u20094.61\u2009\u00d7\u200910\u22125) and breast cancer (odds ratio:\u00a00.94; 95% confidence interval:\u00a00.90\u20130.98; P\u2009=\u2009.003). Sensitivity analysis found little evidence of horizontal pleiotropy. The inverse variance weighted method also detected weak evidence of associations of AAM with endometriosis and pre-eclampsia or eclampsia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This MR study demonstrated a causal effect of AAM on gynecological diseases, especially for breast cancer and endometrial cancer, which indicates AAM might be a promising index to use for disease screening and prevention in clinical practice.<\/jats:p>\n                  <jats:p>Key messages What is already known on this topic \u2013 Observational studies have reported associations between age at menarche (AAM) and a variety of gynecological diseases but the causality has not been determined. What this study adds \u2013 This Mendelian randomization study demonstrated that AAM causally affects the risk of breast cancer and endometrial cancer. How this study might affect research, practice, or policy \u2013 The findings of our study imply that AAM could be a candidate marker for early screening of populations at higher risk of breast cancer and endometrial cancer.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/postmj\/qgad023","type":"journal-article","created":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T14:54:56Z","timestamp":1686495296000},"page":"993-999","source":"Crossref","is-referenced-by-count":13,"title":["Health outcomes of age at menarche in European women: a two-sample Mendelian randomization study"],"prefix":"10.1093","volume":"99","author":[{"given":"Yang","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Medical Intensive Care Unit, Wuhan Asia General Hospital , Wuhan, Hubei, 430056 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Xia","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Hospital of Hubei Province Department of Medical Intensive Care Unit, , Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Medical Intensive Care Unit, Wuhan Asia General Hospital , Wuhan, Hubei, 430056 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiang","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Hospital of Hubei Province Department of Medical Intensive Care Unit, , Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Intensive Care Unit, Wuhan Asia General Hospital , Wuhan, Hubei, 430056 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songbo","family":"Xie","sequence":"additional","affiliation":[{"name":"Jianli People\u2019s Hospital Intensive Care Unit, , Jingzhou, Hubei, 433399 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Hospital of Hubei Province Department of Medical Intensive Care Unit, , Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,10]]},"reference":[{"key":"2023082210050702900_ref1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1196\/annals.1429.026","article-title":"Pubertal development and menarche","volume":"1135","author":"DiVall","year":"2008","journal-title":"Ann N Y Acad 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