Estetrol, a potencial treatment for endometriosis – in vivo study

ZABALA A; VALLCANERAS S; CONFORTI R; DELSOUC M; MONTT-GUEVARA MM; GIANNINI A; SIMONCINI T; CASAIS M

Amsterdam

Congreso; 15th Congress of the European Society of Gynecology; 2023

European Society of Gynecology

Context: Endometriosis (EDT) is a gynecological chronic disease characterized by the growth of endometrial-like tissue outside the uterus. It affects at least 10% of women worldwide, severely impacting their health and life quality. Commonly, it is associated with severe pelvic pain and infertility. Endometriosis is known as an estrogen-dependent and P4-resistant disease, mainly characterized by the alteration in the expression of estrogen (ERs) and progesterone (PRs) receptors. Other studies have proposed that high ERβ levels suppress ERα expression, thus contributing to secondary PR deficiency and progesterone resistance. Estetrol (E4) is a natural estrogen produced only by the fetal liver during pregnancy. Nowadays, it is a potential drug for human use in hormone replacement therapy, osteoporosis, and contraception. E4 is considered a weak estrogen, and to date, there are no studies about E4 as a treatment for EDT in vivo models. Objective: Evaluate the effects of E4 on an experimental model of endometriosis in vivo. Methods: Endometriosis was induced surgically in female C57BL/6 mice. E4 was delivered continuously by Alzet pump (3 mg/kg/day) from the 15th postoperative day. Controls only received the vehicle. Over 4 weeks of treatment, the animals were euthanized. Eutopic lesions were counted, measured with a caliper, removed, and weighed. Analysis of cell proliferation and apoptosis of the tissue was made by PCNA immunohistochemistry and TUNEL, respectively. Determination of receptor expression (Erα, ERβ, and PRAB) was carried out by RT-qPCR. Results: In this study, E4 significantly reduced the volume (p