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Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Hypothyroidism, characterized by reduced thyroid hormone levels, and endometrial cancer, a prevalent gynecological malignancy, have been suggested to have a potential association in previous observational studies. However, the causal relationship between them remains uncertain. This study aimed to investigate the causal relationship between hypothyroidism and endometrial cancer using a bilateral Mendelian randomization approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A bidirectional two-sample Mendelian randomization study was conducted using summary statistics from genome-wide association studies to identify genetic variants associated with hypothyroidism and endometrial cancer. The inverse variance weighting method was used as the main analysis, and sensitivity analyses were conducted to validate the MR results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results of our analysis did not support a causal effect of hypothyroidism (OR: 0.93, p=0.08) or autoimmune hypothyroidism (OR: 0.98, p=0.39) on endometrial cancer risk. In the reverse MR analysis, we did not find a significant causal effect of endometrial cancer on hypothyroidism (OR: 0.96, p=0.75) or autoimmune hypothyroidism (OR: 0.92, p=0.50). Based on subgroup analysis by pathological subtypes of endometrial cancer, the above findings were further substantiated (all p-value &amp;gt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our Mendelian randomization analysis suggests a lack of causal association between hypothyroidism and endometrial cancer. To gain a deeper understanding of this association, it is essential to conduct large-scale randomized controlled trials in the future to validate our findings.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1308208","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T04:37:56Z","timestamp":1715834276000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Assessment of bidirectional relationships between hypothyroidism and endometrial cancer: a two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Bolin","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengnan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinli","family":"Pei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinming","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002108","article-title":"Cancer statistics in China and United States, 2022: profiles, trends, and determinants","volume":"135","author":"Xia","year":"2022","journal-title":"Chin Med J (Engl)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1701\u20132163(15)30970\u20131","article-title":"Epidemiology and investigations for suspected endometrial cancer","volume":"35","author":"Renaud","year":"2013","journal-title":"J Obstet Gynaecol Can"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.009","article-title":"Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"33","author":"Oaknin","year":"2022","journal-title":"Ann Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.987401","article-title":"Hypothyroidism has a protective causal association with hepatocellular carcinoma: A two-sample Mendelian randomization study","volume":"13","author":"Lu","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2018.0224","article-title":"Relationship between hypothyroidism and endometrial cancer","volume":"10","author":"Wang","year":"2019","journal-title":"Aging Dis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.jmig.2015.02.017","article-title":"Long-term clinical outcomes after resectoscopic endometrial ablation of nonatypical endometrial hyperplasia in women with abnormal uterine bleeding","volume":"22","author":"Vilos","year":"2015","journal-title":"J Minim Invasive Gynecol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13215444","article-title":"Does clinical and biochemical thyroid dysfunction impact on endometrial cancer survival outcomes? 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