Neuroprotective effects of estetrol in combined oral contraceptives: A review

One of the most effective contraception methods is combined hormonal contraceptives. According to the current prescribing information, in addition to their primary effect, they have several concomitant positive effects on the female body – non-contraceptive effects. These include a well-predictable and controlled "menstrual cycle" (menstrual-like reaction), anti-androgenic effect, anti-anemic effect due to reduced menstrual blood loss, reducing the severity of dysmenorrhea and premenstrual syndrome, reducing the risk of pelvic inflammatory diseases, ectopic pregnancy, and some benign and malignant tumors of the reproductive system. Combined oral contraceptives (COCs) also have effects on the central nervous system, hypothalamic-pituitary structures that regulate sex hormones, and the psycho-emotional health of women. For a long time, the main estrogen component of COCs remained ethinylestradiol. Although not well-studied, its mechanisms of action on the nervous system are similar, regardless of the progestogen component. However, the effect was not entirely positive: taking contraceptives containing ethinylestradiol can lead to increased emotional lability, anxiety, and depressive disorders. It drives researchers to search for new estrogen without these adverse properties. Such is the long-known but overlooked esthetrol. Numerous studies indicate a pronounced neuroprotective effect of esthetrol, which can increase patients' satisfaction with hormonal contraceptives and their compliance. It also opens up great opportunities for the use of this drug beyond gynecological practice.