Estetrol

Estetrol (E4), or 15α-hydroxyestriol, is an estrogen steroid hormone, found in detectable levels in maternal serum at around week 20.

Estetrol is a human steroid, produced by the fetal liver during pregnancy only. This natural hormone was discovered in urine of pregnant women by Diczfalusy and coworkers in 1965. Estetrol has the structure of an estrogenic steroid with four hydroxyl groups which explains the acronym E4. Estetrol is synthesized in the fetal liver from estradiol (E2) and estriol (E3) by the two enzymes 15α- and 16α-hydroxylase. After birth the neonatal liver rapidly loses its capacity to synthesize E4 because these two enzymes are no longer expressed.

Estetrol reaches the maternal circulation through the placenta and was already detected at nine weeks of pregnancy in maternal urine. During the second trimester of pregnancy high levels were found in maternal plasma, with steadily rising concentrations of unconjugated E4 to about 1 ng/mL (> 3 nmol/L) towards the end of pregnancy. So far the physiological function of E4 is unknown. The possible use of E4 as a marker for fetal well-being has been studied quite extensively. However, due to the large intra- and inter-individual variation of maternal E4 plasma levels during pregnancy this appeared not to be feasible.