Test Catalog

Test ID: UE3    
Estriol, Unconjugated, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

A part of second trimester or cross-trimester biochemical screening for Down syndrome and trisomy 18 syndrome


A marker of fetal demise


An adjunct biomarker in the prenatal diagnosis of disorders of fetal steroid metabolism, including Smith-Lemli-Opitz syndrome (SLO)(3-4), and X-linked ichthyosis (placental sulfatase deficiency disorders)


Evaluating primary or secondary fetal adrenal insufficiency after excluding other rare single gene defects, including aromatase deficiency, 17 alpha-hydroxylase deficiency and/or various forms of congenital adrenal hyperplasia

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Estrogens are involved in development and maintenance of the female phenotype, germ cell maturation, and pregnancy. There are 3 major biologically active estrogens in humans: estrone (E1), estradiol (E2), and estriol (E3). Like all members of the steroid hormone family, they diffuse into cells and bind to specific nuclear receptors, which in turn alter gene transcription in a tissue specific manner. E2 is the most potent natural human estrogen, closely followed by E1, while E3 possess only 20% of the E2 affinity for the estrogen receptor. In men and nonpregnant women, E1 and E2 are formed from the androgenic steroids androstenedione and testosterone, respectively. E3 is derived largely through conversion of E2, and to a lesser degree from 16a-metabolites of E1. E2 and E1 can also be converted into each other, and both can be inactivated via hydroxylation and conjugation.


During pregnancy E3 becomes the dominant estrogen. The fetal adrenal gland secretes dehydroepiandrosterone-sulfate (DHEAS), which is converted to E3 in the placenta and diffuses into the maternal circulation. The half-life of unconjugated E3 (uE3) in the maternal blood system is 20 to 30 minutes since the maternal liver quickly conjugates E3 to make it more water soluble for urinary excretion. E3 levels increase throughout the course of pregnancy, peaking at term.


Decreased second trimester uE3 has been shown to be a marker for Down and trisomy-18 syndromes. uE3 is a part of multiple marker prenatal biochemical screening, together with alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and inhibin-A measurements. Low levels of uE3 also have been associated with pregnancy loss, Smith-Lemli-Opitz syndrome (defect in cholesterol biosynthesis), X-linked ichthyosis and contiguous gene syndrome (placental sulfatase deficiency disorders), aromatase deficiency, and primary or secondary fetal adrenal insufficiency.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Males: <0.07 ng/mL

Females: <0.08 ng/mL


For SI unit Reference Values, see International System of Units (SI) Conversion

Interpretation Provides information to assist in interpretation of the test results

In second trimester maternal serum screening (QUAD), , unconjugated E3 (uE3) forms part of a complex, multivariate risk calculation formula, using maternal age, gestational stage, and other demographic information, in addition to the results of the biochemical markers, for Down syndrome and trisomy 18 risk calculation.


A serum uE3 <0.15 multiples of the gestational age median in women, who otherwise screen negative in the quad test, can indicate Smith-Lemli-Opitz syndrome and X-linked ichthyosis.


A low uE3 level can indicate the possibility of aromatase deficiency, congenital adrenal hyperplasia, primary or secondary (including maternal corticosteroid therapy) fetal adrenal insufficiency and/or fetal demise.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Like any immunoassay, this test can occasionally be subject to analytical interferences. Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating anti-animal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results. If the clinical picture is inconsistent with the test results, clinicians should consider the possibility of a preanalytical or analytical error and contact the laboratory.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Thaniyaporn S, Chanane W, Supatra S, et al: Association between isolated abnormal levels of maternal serum unconjugated estriol in the second trimester and adverse pregnancy outcomes. J Matern Fetal Neonatal Med. 2016;29:13, 2093-2097

2. Minsart AF, Van Onderbergen A, Jacques F, et al: Indication of prenatal diagnosis in pregnancies complicated by undetectable second-trimester maternal serum estriol levels. J Prenat Med. 2008;2(3):27-30

3. Bradley LA, Palomaki GE, Knight GJ, et al: Levels of unconjugated estriol and other maternal serum markers in pregnancies with Smith Lemli Opitz (RSH) syndrome fetuses [letter]. Am J Med Genet 1999;82:355-358

4. Reisch N, Idkowiak J, Hughes B,Prenatal Diagnosis of Congenital Adrenal Hyperplasia Caused by P450 Oxidoreductase Deficiency. J Clin Endocrinol Metab. 2013 Mar;98(3):E528-E536. doi: 10.1210/jc.2012-3449

5. Yarbrough ML, Stout M, Gronowski AM: Ch 69 Pregnancy and Its Disorders. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Sixth edition. Edited by N Rafai, AR Horvath, CT Wittwer. Elsevier, 2018, pp 1655-1696