The effect of androgens on the risk of endometriosis sub-phenotypes and ovarian neoplasms : a Mendelian randomization study

Gjorgoska, Marija (author), Lanišnik-Rižner, Tea (author)

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.

• Language: English
• Keywords: androgen hormones, endometriosis sub-phenotypes, ovarian neoplasms, two-sample Mendelian randomization
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 9 str.
• Numbering: Vol. 239, art. 106482
• PID: 20.500.12556/RUL-156244
• UDC: 616-006:577
• ISSN on article: 1879-1220
• DOI: 10.1016/j.jsbmb.2024.106482
• COBISS.SI-ID: 187494659
• Publication date in RUL: 15.05.2024

Record is a part of a journal

• Title: The journal of steroid biochemistry and molecular biology
• Shortened title: J. steroid biochem. mol. biol.
• Publisher: Elsevier
• ISSN: 1879-1220
• COBISS.SI-ID: 57401603

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: androgeni hormoni, subfenotipi endometrioze, novotvorbe jajčnikov, Mendlova randomizacija dveh vzorcev