20.500.12556/RUL-156244 The effect of androgens on the risk of endometriosis sub-phenotypes and ovarian neoplasms a Mendelian randomization study Endometriosis is a complex gynecological pathology with a broad spectrum of symptoms, affecting around 10% of reproductive-aged women. Ovarian cancer (OC) is a heterogeneous disease for which we lack effective diagnostic and therapeutic strategies. The etiology and pathogenesis of both diseases remain ambiguous. Androgens in endometriosis could have a distinct role beyond serving as estrogen sources, whereas in the case of serous OC could be important in the formation of precursor lesions which ultimately lead to tumor formation. Here we performed two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the androgen precursor - dehydroepiandrosterone sulphate (DHEAS), bioactive androgen - testosterone (T), androgen metabolite - androsterone sulphate, steroid hormone binding globulin (SHBG) and albumin and the risk of endometrioses of various sub-phenotypes and ovarian neoplasms across the benign-borderline-malignant spectrum. Stringent quality control procedures were followed to select eligible instrumental variables that were strongly associated with the selected exposures, sensitivity analyses were performed to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis and ovarian neoplasms. We discovered an inverse association between genetically predicted levels of all androgens and risk of endometriosis, the same trend was most evident in the ovarian sub-phenotype. Total T levels were also inversely associated with peritoneal sub-phenotype of endometriosis. Likewise, T was causally associated with decreased risk of clear-cell OC, an endometriosis-associated OC subtype, and with malignant serous OC of both low- and high-grade, but with higher risk of their counterpart of low malignant potential. These findings support further investigation of androgen's action at a molecular level in ovary-associated endometriotic lesions, clear cell ovarian tumors and serous precursor lesions. androgen hormones endometriosis sub-phenotypes ovarian neoplasms two-sample Mendelian randomization androgeni hormoni subfenotipi endometrioze novotvorbe jajčnikov Mendlova randomizacija dveh vzorcev true false true Angleški jezik Slovenski jezik Članek v reviji 2024-05-15 14:03:23 2024-05-15 14:03:29 2024-05-16 03:53:24 0000-00-00 00:00:00 2024 0 0 9 str. art. 106482 Vol. 239 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006:577 1879-1220 10.1016/j.jsbmb.2024.106482 187494659 1-s2.0-S096007602400030X-main.pdf 1-s2.0-S096007602400030X-main.pdf 1 E85AA29B1D43C4F6870C74946235A3F5 97fa533fe8ddf55602dc3c303b3e65e7f5220ba1660c7e71f2e33002f94e4e51 690ebe66-12b3-11ef-af1f-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=183601 https://www.sciencedirect.com/science/article/pii/S096007602400030X 0 241206bc-12b3-11ef-af1f-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=183600 Medicinska fakulteta 0 0 0