Estriol

The Estriol (E3) assay—also referred to as free estriol or unbound estriol—is used to appraise placental performance and fetal status, particularly in pregnancies complicated by preeclampsia, fetal growth restriction, diabetes, Rh isoimmunization, and trophoblastic disease (hydatidiform mole, choriocarcinoma). As part of second‑trimester maternal serum screening with alpha‑fetoprotein and hCG, estriol contributes to risk estimation for trisomy 21, trisomy 18, and open neural tube defects. Serial measurements are preferred for clinical decision‑making. Low concentrations may be seen with anencephaly or placental sulfatase deficiency, whereas levels can be higher with multiple gestation. Outside pregnancy, marked elevations may occur with estrogen‑producing tumors of the ovary, testis, or adrenal.

Unconjugated estriol is the dominant estrogen of normal gestation and reflects the integrated activity of the fetus and placenta. Because the placenta lacks a complete steroidogenic pathway, it relies on precursors—primarily maternal and fetal DHEA‑S—with approximately 90% of placental estriol originating from fetal liver metabolism. Maternal serum concentrations increase as pregnancy advances and show diurnal fluctuation; interpretation requires gestational age–specific context, with preference for serial trends over isolated results. Reduced estriol may occur with anencephaly or placental sulfatase deficiency, while higher values are expected in multiple gestations. Estriol is included with alpha‑fetoprotein and hCG in second‑trimester screening to estimate the probability of common chromosomal abnormalities and structural defects. Markedly elevated values outside pregnancy can be associated with estrogen‑secreting neoplasms of the ovary, testis, or adrenal. Single measurements are difficult to interpret; trend analysis is generally more informative.