2024 Volume 71 Issue 5 Pages 543
Dear Editor,
In February 2024, Wakatsuki’s group published an exciting article in this journal evaluating the effect of estetrol on the invasion of endometrial cells [1]. However, there is an essential reference that is not incorporated and supports the results and conclusions of the authors. In April 2023, the article called “Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures” was published by Patino-Garcia et al. Here, the researchers use the wound method to evaluate the effect of estetrol on the migration of 11Z and Hs832 cells, which correspond to human endometrial epithelium and stroma. After 48 hours of incubation, estetrol did not show significant differences compared to the control, and on the contrary, incubation with estradiol significantly increased cell migration in both lines [2].
On the other hand, Wakatsuki’s study uses the wound assay in shorter times (8 hours) and incorporates the matrigel invasion assay and a cell tracking analysis, which strengthens the article’s conclusions [1]. Furthermore, the study is not limited to characterizing the effects of estetrol on the cells under study. Instead, it showed how estetrol could inhibit the action of estradiol, alluding to the anti-estrogenic role of this molecule due to its weak affinity for estrogen receptors. Similar results have been found in breast cancer, where estetrol has antiestrogenic effects in those tumors that express the estrogen receptor alpha [3].
Estetrol is a natural estrogen produced by the fetal liver during pregnancy and reaches values of up to 1.02 ng/mL in maternal serum [4]. It is currently used as a contraceptive treatment and to reduce menopause symptoms. Additionally, studies continue to evaluate its use in breast cancer due to the antiestrogenic effect reported. Therefore, the role of estetrol in each known estrogen-dependent pathology will likely be evaluated, and new potential uses will be determined from in vitro studies onwards.
In summary, Wakatsuki’s article confirms the findings of the article mentioned above [2] and goes one step further by showing an antiestrogenic effect when combining estetrol with estradiol. In this way, it is suggested that this reference be considered, given that it supports the solid development of science when complementary results emerge from independent research teams from different parts of the world.
