Free estriol (E3)

Why this test?

To assess the state of the fetoplacental complex (diagnosis of placental insufficiency, intrauterine fetal development delay, intrauterine fetal death).

To assess the risk of developing frequent fetal anomalies - Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and neural tube defects.

To assess the risk of developing rare fetal diseases: adrenal insufficiency, X-linked ichthyosis and Smith-Lemli-Opitz syndrome.

To assess the risk of developing complications of the third trimester of pregnancy: premature detachment of the placenta and preeclampsia.

For the diagnosis of hormonally active tumors of the ovary, testicle and adrenal glands.

In what cases is it prescribed?

During pregnancy monitoring, in particular, in the presence of risk factors for the development of fetal abnormalities (age over 35 years, multiple pregnancy, the presence of fetuses with chromosomal abnormalities in the obstetric history, concomitant HIV infection, pregnancy resulting from IVF, smoking and diabetes).

When a pregnant woman is examined to assess the risk of developing complications in the third trimester of pregnancy (premature detachment of the placenta and preeclampsia).

With symptoms of late toxicosis: with headache, dizziness, visual impairment, tinnitus, edema, hypertension.

With symptoms of hyperestrogenism: uterine bleeding in case of women and gynecomastia in case of men.

Test information

Estriol is one of the three main estrogens.

In terms of activity, it is significantly inferior to estradiol and estrone, and its role in the body of a non-pregnant woman is small.

However, with the onset of pregnancy, it becomes the main estrogen and ensures its normal course. Estriol stimulates the synthesis of vasodilating prostaglandins in endometrial cells and enhances uteroplacental blood flow. In addition, it increases the receptor-mediated uptake of low-density lipoprotein cholesterol for subsequent synthesis of progesterone by the placenta, and also stimulates the growth of the mammary gland.

Estriol, synthesized during pregnancy, is the final product of a complex chain of biochemical transformations that reflects the close relationship between the fetus, placenta and mother. The placenta does not have the full set of enzymes it needs to synthesize estrogens from cholesterol, so it uses ready-made estrogen precursors that come from both the fetus and the mother. One of these precursors is dehydroepiandrosterone sulfate (DHEA-S), which is synthesized in the adrenal glands of the mother and in the fetal adrenal cortex of the fetus. When DHEA-S is metabolized in the placenta, estradiol and estrone are formed, but only a small fraction is converted to estriol. About 90% of placental estriol is formed from DHEA-S metabolites formed in the fetal liver. In this regard, the serum estriol concentration is used as an indicator of the condition of the fetus, as well as the placenta.

Estriol, which is synthesized in the placenta, is called free (unconjugated). An increase in the concentration of estriol can be detected already at the earliest stages of pregnancy - with the beginning of the formation of the placenta, therefore the determination of free estriol is used as a pregnancy test. However, in terms of sensitivity and specificity, it is inferior to the pregnancy test using the beta subunit of human chorionic gonadotropin (beta-hCG). Analysis of free estriol is indicated for all pregnant women to exclude the three most common chromosomal and structural abnormalities of the fetus: trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and neural tube defects.

Risk factors for the development of fetal abnormalities include: giving birth at the age of over 35, multiple pregnancy, the presence in the obstetric history of fetuses with chromosomal abnormalities (trisomy 21, 13 or 18), concomitant HIV infection, pregnancy resulting from IVF, smoking and diabetes. At the same time, the age of the mother is the most significant factor.
Thus, the risk of the development of chromosomal abnormalities of the fetus increases sharply after 35 years (1: 179 compared to 1: 476 in a 25-year-old woman).

For the most accurate diagnosis of chromosomal and structural abnormalities of the fetus, clinical and laboratory indicators are used - free estriol in combination with beta-hCG and alpha-fetoprotein (alpha-FP). The blood serum test is carried out in the second trimester of pregnancy at 15-20 weeks (the optimal period is 15-17 weeks). The results of such a triple test, as well as other factors (age, smoking, weight, ethnicity, heavy obstetric history) are used to calculate the probability of fetal abnormalities. It should be noted that tests for free estriol, beta-hCG and alpha-FP as a screening for fetal abnormalities allow for an accurate assessment of the risk of developing abnormalities in the early stages. The results of the test are taken into account when making a decision on termination or continuation of pregnancy.

There are a number of other diseases of the fetus and mother that lead to changes in the level of free estriol. Its decrease is characteristic of rare but severe disorders of the fetus - adrenal insufficiency, X-linked ichthyosis, Smith - Lemli - Opitz syndrome. A low concentration of free estriol in combination with high levels of beta-hCG and alpha-FP is associated with an increased risk of delayed intrauterine development of the fetus and complications of the third trimester of pregnancy (premature detachment of the placenta and preeclampsia).

The main source of estrogen in a woman's body is the ovaries. When estrogen-producing ovarian tumors occur, the levels of free estriol and other estrogens increase many times, which causes hyperestrogenism. The most frequent hormonally active tumors of the ovary are malignant granulosa cell tumor and benign thecoma. In most cases, they occur in women after menopause. As a result of hyperestrogenism, there is excessive stimulation of endometrial cells, which leads to hyperplasia and adenocarcinoma. Both diseases are manifested by uterine bleeding. In men, female sex hormones are formed mainly from adipose tissue, but the testicles also produce a small amount of them. With hormonally active testicular tumors, hyperestrogenism develops, which leads to gynecomastia. Hormonally active tumors make up about 1% of all testicular neoplasms, the most common are Sertoli cell tumors and granulosa cell tumors. They are often bilateral and rarely metastasize. Another cause of increased levels of free estriol and other estrogens in men and women is adrenal tumor.