Estetrol Inhibits Endometriosis Development in an In Vivo Murine Model

Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E) is a weak estrogen that recently has been approved for contraception. We evaluated the effect of E on the growth of endometriotic-like lesions and the expression of TNF-α, estrogen receptors (ERs), and progesterone receptors (PRs) in an in vivo murine model. Endometriosis was induced surgically in female C57BL/6 mice. E was delivered via Alzet pump (3 mg/kg/day) from the 15th postoperative day for 4 weeks. E significantly reduced the volume ( < 0.001) and weight ( < 0.05) of ectopic lesions. Histologically, E did not affect cell proliferation (PCNA immunohistochemistry) but it did increase cell apoptosis (TUNEL assay) ( < 0.05). Furthermore, it modulated oxidative stress (SOD, CAT, and GPX activity, < 0.05) and increased lipid peroxidation (TBARS/MDA, < 0.01). Molecular analysis showed mRNA (RT-qPCR) and protein (ELISA) expression of TNF-α decreased ( < 0.05) and mRNA expression of reduced ( < 0.05), in contrast with the increased expression of ( < 0.01) and ( < 0.05). The present study demonstrates for the first time that E limited the development and progression of endometriosis in vivo.