Most of the estriol circulating or excreted during the third trimester of pregnancy is the joint product of fetus and placenta, originating from a precursor synthesized in the fetus by the adrenal glands, and transformed by the fetal liver and the placenta into estriol. On traversing the placenta, this is rapidly metabolized, primarily in the maternal liver, to conjugated forms: the estriol sulfates and glucuronides. As a result, "free" estriol, the unconjugated form, accounts for barely nine percent of the total estriol in circulation; the estriol sulfates, which are relatively long-lived, account for roughly half. Urinary estriol consists entirely of conjugated forms since only free estriol enters the maternal circulation while only the conjugated forms are excreted.
In combination with other techniques for fetal surveillance, serial determinations have been used in the management of pregnancies complicated by diabetes, hypertension, prolonged gestation and uncertain dates. These clinical applications have been recently reviewed.
There is considerable patient-to-patient variability: the reference range for a given gestational age may encompass estriol levels from 50 to 200 percent of the median for that age. Hence the pattern generated by serial determinations is ordinarily of greater significance than the results of isolated measurements. Persistently low or rapidly falling estriol levels suggest fetal distress. However, because estriol concentrations are subject to diurnal and episodic variation, it is common practice to refer serum measurements to a baseline, defined for the patient as either the average or the highest of her three most recent estriol results. A drop of 40 percent or more relative to this baseline is likely to be significant.
Normally, as the fetus develops, estriol production increases, resulting in a nearly three-fold rise in circulating estriol levels during the final trimester, and a corresponding increase in urinary levels. There is typically a surge at about the 36th week. According to the literature, free and total estriol concentrations reach approximately 15 and 250 ng/mL at term, while the urinary output climbs to approximately 45 mg/day. After 40 weeks, estriol levels gradually subside, declining by roughly 12 percent per week.