IMS Menopause Live

Estetrol a promising native estrogen for oral contraception and the relief of menopausal symptoms

23 May 2022

Summary

The use of hormonal therapy has been associated with an increased risk of venous thromboembolism (VTE) and breast cancer. Recently, Gérard et al. [1] reported in a narrative review the profile of estetrol (E4), an estrogen produced by the human fetal liver, with properties that may provide a better safety profile. Unlike other estrogens, E4 activates the nuclear estrogen receptor (ER) α signaling pathway but does not activate membrane ERα signaling pathway in specific tissues. It is considered the first Native Estrogen with Selective action in Tissues (NEST) due to its differential activation of the nuclear and membrane ERα pathways. E4 does not stimulate the membrane ERα and antagonizes the estradiol-induced membrane effects. E4 has recently been approved in Europe and several countries (USA, Canada, Australia) as a new estrogenic component of a combined oral contraceptive, associated with drospirenone. The association of 15 mg of E4 plus drospirenone 3 mg has good contraceptive efficacy, safety, and user tolerability. E4 has a low impact on the liver and the breast, and a higher effect on the endometrium, vaginal epithelium, and the cardiovascular system. In comparison to other contraceptives, the association of E4/drospirenone showed less impact on several parameters, including laboratory markers of hypercoagulability. Finally, in addition to its use in contraception, E4 has the potential to be used in the treatment for menopausal symptoms.

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