Abstract
Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERβ, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.
Highlights
Estetrol (E4) is a human natural estrogen which was discovered in 1965 in urines of pregnant women [1,2]
(20 mg E4/LNG like EE/DRSP) Endometrial thickness suppressed in all groups Post-treatment ovulation occurred in all patients in the first month
Lowest frequency of unscheduled bleeding and/or spotting and absence of withdrawal bleeding in the 15 mg E4/DRSP group
Summary
Estetrol (E4) is a human natural estrogen which was discovered in 1965 in urines of pregnant women [1,2]. It is only produced during human pregnancy and it reaches the maternal circulation through the placenta [3,4]. Human maternal plasma levels increase during pregnancy, reaching high concentrations towards the end of gestation (≥1 ng/mL). Fetal plasma levels have been reported to be nearly 20 times higher than maternal plasma levels at parturition [5]. The role as a marker of fetal health have been studied for many years but no correlation was found [7,8]. In this review we summarize the actual knowledge about E4, focusing the attention on its new application for hormonal contraception
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