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

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

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.

• Jezik: Angleški jezik
• Ključne besede: androgen hormones, endometriosis sub-phenotypes, ovarian neoplasms, two-sample Mendelian randomization
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 9 str.
• Številčenje: Vol. 239, art. 106482
• PID: 20.500.12556/RUL-156244
• UDK: 616-006:577
• ISSN pri članku: 1879-1220
• DOI: 10.1016/j.jsbmb.2024.106482
• COBISS.SI-ID: 187494659
• Datum objave v RUL: 15.05.2024

Gradivo je del revije

• Naslov: The journal of steroid biochemistry and molecular biology
• Skrajšan naslov: J. steroid biochem. mol. biol.
• Založnik: Elsevier
• ISSN: 1879-1220
• COBISS.SI-ID: 57401603

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: androgeni hormoni, subfenotipi endometrioze, novotvorbe jajčnikov, Mendlova randomizacija dveh vzorcev