Estradiol, Estriol, and Estrogen measurements are used to evaluate sexual maturity, menstrual problems, and fertility problems in females. Estrogen Levels are also used in the evaluation of males with gynecomastia or feminization syndromes. In pregnant women it is used to indicate fetal-placental health. In patients with estrogen-producing tumors it can be used as a tumor marker.
There are three major estrogens. E2 (estradiol) is predominantly produced in the ovary. In females there is a feedback mechanism for the secretion of E2. Low levels of E2 stimulate the hypothalamus to produce gonadotropin-releasing factors. These hormone factors stimulate the pituitary to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These two hormones stimulate the ovary to produce E2, which peaks during the ovulatory phase of the menstrual cycle. This hormone is measured most often to evaluate menstrual and fertility problems, menopausal status, sexual maturity, gynecomastia, and feminization syndromes or as a tumor marker for patients with certain ovarian tumors.
E1 (estrone) is also secreted by the ovary, but most is converted from androstenedione in peripheral tissues. Estrone is a more potent estrogen than estriol but is less potent than estradiol. Estrone is the major circulating estrogen after menopause.
E3 (estriol) is the major estrogen in the pregnant female. Serial urine and blood studies of estriol excretion provide an objective assessment of placental function and fetal normality in high-risk pregnancies. Excretion of estriol increases around the eighth week of gestation and continues to rise until shortly before delivery. Estriol is produced in the placenta from estrogen precursors, which are made by the fetal adrenal gland and liver. The measurement of excreted estriol is an important index of fetal well-being. Rising values indicate an adequately functioning fetoplacental unit. Low levels may indicate Fetoplacental Deterioration (failing pregnancy, dysmaturity, preeclampsia/eclampsia, complicated diabetes mellitus, anencephaly, of fetal death) and require prompt reassessment of the pregnancy. If the estriol levels fall, early delivery of the fetus may be indicated.
Serial studies usually begin at approximately 28 to 30 weeks of gestation and are then repeated weekly. The frequency of these estriol determinations can be increased as needed to evaluate a high-risk pregnancy. Collection may be done daily. Although the first collection is the baseline value, all collection results are compared with previous ones, because decreasing values suggest fetal deterioration. Some physicians use an average of three previous values as a control value.
Estriol excretion studies can be done using 24-hour urine tests or blood studies. Because urinary creatinine excretion is relatively constant, creatinine clearance is often simultaneously tested to assess the adequacy of the 24-hour urine collection for estriol. A serially increasing estriol/creatinine ratio is a favorable sign in pregnancy. Plasma estriol determinations also can be used to evaluate the fetoplacental unit. These studies can conveniently and rapidly assess the quantity of free estriol in the plasma by radioimmunoassay (RIA). The plasma collected by venipuncture is an accurate reflection of the current status of the placenta and fetus. The advantage of the plasma estriol determination is that it is more easily obtained than a 24-hour urine specimen and is less affected by medications. All the estrogens can be measured by gas chromatography, but RIA techniques are more accurate and less affected by drugs or birth control pills.
Unfortunately only severe placental distress will decrease urinary estriol sufficiently to reliably predict fetoplacental stress. Furthermore, plasma and urinary estriol levels are normally associated with a significant daily variation, which may confuse serial results.
Maternal illnesses, such as hypertension, preeclampsia, anemia, and impaired renal function, can also factitiously decrease urinary estriol levels. Because these problems create a high number of false-positive and false-negative findings, most clinicians now use nonstress fetal monitoring to indicate fetal-placental health.
Normal Estradiol Levels
Normal Estradiol Levels are the lowest in children and the highest in adult females during the menstrual cycle. Estradiol Levels can be measured either in serum or in urine, the following is a listing of the Normal Estradiol Levels ranges:
Children younger than 10 years of age:
Normal Estradiol Level in serum should be less than 15 pg/mL.
Normal Estradiol Level in 24 hours urine collection is none or less than 7 mcg (micrograms).
Normal Estradiol Level in serum should range between 10 and 50 pg/mL.
Normal Estradiol Level in 24 hours urine collection is none or less than 7 mcg.
During Follicular Phase:
Normal Estradiol Level in serum should range between 20 and 350 pg/mL.
Normal Estradiol Level in 24 hours urine collection is none or less than 13 mcg.
At Mid-cycle Peak
Normal Estradiol Level in serum should range between 150 and 750 pg/mL.
Normal Estradiol Level in 24 hours urine collection should range between 4 and 14 mcg.
During Luteal Phase
Normal Estradiol Level in serum should range between 30 and 450 pg/mL.
Normal Estradiol Level in 24 hours urine collection should range between 4 and 14 mcg.
Normal Estradiol Level in serum should be equal to or less than 20 pg/mL.
Normal Estradiol Level in 24 hours urine collection s none or less than 7 mcg.
Normal Estriol Levels
Normal Estriol Levels in urine for adult maless and children yonger than 10 of age are nothing or up to 14 mcg in a 24 hours collection. The following is a listing of Normal Estriol Levels in urine for females during the follicular phase per 24 hours urine collections:
- During Ovulatory Phase: Between 13 and 54 mcg.
- During Luteal Phase: Between 8 and 60 mcg.
- Postmenopausal: None or up to 11 mcg.
Normal Estriol Levels For Pregnant Females
During the First Trimester:
Normal serum levels should be less 38 ng/mL.
Normal Estiol Levels in a 24 hours urine collection range between 0 and 800 mcg.
During the Second Trimester :
Normal Estriol Levels in serum range between 38 and 140 ng/mL.
Normal Estiol Levels in a 24 hours urine collection range between 800 and 12000 mcg.
During Third Trimester:
Normal Estriol Levels in serum range between 31 and 460 ng/mL.
Normal Estiol Levels in a 24 hours urine collection range between 5000 and 12000 mcg.
Normal Total Estrogen Levels
Normal Total Estrogen Levels for adult male and child younger than 10 years of age range between 4 and 25 mcg per 24 hours urine collection. A female who is not pregnant will have normal Estrogen Levels range between 4 and 60 mcg in a 24 urine collection.
Normal Total Estrogen Levels for Pregnant Females
The following is a listing of the Normal Total Estrogen levels for pregnant females in 24 hours urine collection during each trimester of pregnancy:
1st Trimester: None or up to 800 mcg.
2nd Trimester: Between 800 and 5000 mcg.
3rd Trimester: Between 5000 and 50,000 mcg.
Causes of High Levels of Estrogens
- Feminization Syndromes: Estrogens are increased in these syndromes for a variety of reasons. The male begins to develop female secondary sex characteristics.
- Precocious Puberty: Children who develop secondary sexual characteristics at an abnormally early age often have a genetic defect in adrenal cortisol metabolism. As a result, large amounts of sex steroid precursors accumulate and are converted to estrogens by the ovary. This causes precocious secondary sexual changes.
- In Gonadal Tumors, granulosa, thecal cells, or fibrocytes secrete estrogens which cause high high Estrogengs Levels observed in Ovarian Tumor, Testicular Tumor, and Adrenal Tumor. The higher the levels, the greater the tumor burden. In these instances estrogen can act as a tumor marker that can be used to monitor the disease.
- Pregnancy: E3 is the main estrogen elevated during pregnancy, although E1 and E2 are also elevated. Multiple pregnancies are associated with particularly high levels of E3.
- Estrogens are catabolized, in part, by the liver. If liver function is deficient (as a result of Hepatic cirrhosis, or Liver necrosis), estrogens and their precursors accumulate. Adult feminization can result.
- Hyperthyroidism: An estrogen-related increase in the production of thyroid-binding globulin produces an elevation of serum total T4.
Causes of Low Estrogens Levels
- A Failing Pregnancy is associated with reduced placental production of E3: Any disease that causes fetal distress, dysmaturity, Rh isoimmunization, preeclampsia/eclampsia, anencephaly, or fetal death will be associated with reduced E3 levels.
- Turner’s Syndrome: This syndrome is seen in females who are missing one X chromosome. They have gonadal dysgenesis to varying degrees.
- Menopause: With normal age-related ovarian failure, estrogen (especially E1) levels decline.
- Anorexia nervosa: Reduction in fat intake reduces sterol precursors available for estrogen synthesis.
Diseases affecting the organs involved in the synthesis of sex hormones anywhere in the hypothalamus/pituitary/gonadal axis will be associated with Low estrogen levels. Such diseases include:
- Primary and Secondary Hypogonadism.
- Stein-Leventhal Syndrome.