Estrogens = Estrone E1, Estradiol E2, Estriol E3
November 13, 2022Chemical pathologyLab Tests
Sample for Estrogens
- It is done on the patient’s serum, which is separated immediately.
- It can be stored at 2 to 8 °C for 2 days in a glass test tube.
- Get a sample regarding the menstrual cycle.
Indications for Estrogens
- Estrogen level is estimated to assess sexual maturity.
- To assess menstrual problems.
- To assess fertility problems.
- In males to assess the gynecomastia and feminization syndrome.
- In pregnant women, assess fetal health.
- This can be done as a tumor marker in the hormone estrogen-producing tumors.
Pathophysiology of Estrogens
- There are three major estrogens:
- Estrone (E1).
- Estradiol (E2). This is predominantly ovarian estrogen.
- Estriol (E3).
- Estrogen consists of C18 steroids. At the same time, progesterone is a C21 steroid.
- All of these estrogens are derived from androgenic precursors like DHEA, and androstenedione. These are synthesized by the adrenal cortex, ovaries, and testis.
- Estrogens are the sex hormone responsible for the following:
- The development and maintenance of female sex organs.
- Female secondary sex characters.
- The most potent estrogen is estradiol E2 secreted by the ovaries. Its measurement is sufficient to evaluate ovarian function.
- Ovaries lack 21-hydroxylase and 11-β-hydroxylase, so they can not produce glucocorticoids and mineralocorticoids like the adrenal cortex.
- Human ovaries produce sex steroids, estrogen, progesterone, and androgens.
- Estrogen’s main site for inactivation in the liver.
- The main biochemical reactions are hydroxylation, oxidation, and methylation.
- Estrogen source:
- The main source of estrogen in pregnant women is the placenta, which is in mg. This is mainly the estriol.
- The main source in non-pregnant women is the ovary in µg quantity. This is mainly estradiol.
- Functions of the estrogen hormone:
- It develops and maintains the female sex organs.
- It develops secondary sex characters.
- It regulates the menstrual cycle (with the help of progesterone).
- Maintain breast and uterus growth.
- It maintains pregnancy.
- It also helps calcium homeostasis and has a beneficial effect on bone.
- It also accelerates linear bone growth and results in epiphyseal closure.
- Depletion of estrogen for a long time leads to:
- Loss of bone mineral contents.
- There are increased stress fractures.
- There is postmenopausal osteoporosis.
- Estrogens are secreted by:
- Ovarian Follicles.
- Corpus luteum from the ovary.
- Placenta during pregnancy.
- A minute amount is produced from:
- Adrenal glands.
- Estradiol and progesterone are the main secretory products of the ovary.
- More than 20 estrogens are identified, but only three have clinical significance and these are:
- Estrone (E1).
- Estradiol (E2).
- Estriol (E3).
- It is a more potent hormone and is predominantly produced in the ovary. It exists in a reversible state with estrone.
- Estrone has a weaker biological function.
- The final product is estriol (E3), a steroid without biological activity.
- E2 is produced exclusively by the ovary; its measurement is often considered sufficient to evaluate ovarian function.
- The low estradiol level stimulates the hypothalamus to produce a gonadotropin hormone-releasing factor.
- These hormones stimulate the pituitary to produce a Follicular stimulating hormone (FSH) and luteinizing hormone (LH).
- These two hormones (FSH and LH) stimulate the ovary to produce E2, which will provide the peak during the ovulatory phase.
- Estradiol transport in blood:
- 97% of the estradiol E2 in the blood is bound to plasma proteins.
- It has a high affinity and is specifically mainly bound to sex hormone-binding globulins (SHBG).
- Nonspecifically bound to albumin.
- SHBG increases by the estrogens, so these are higher in females than males.
- Estradiol E2 significance:
- Menstrual and fertility problems.
- Menopausal status.
- Sexual maturity.
- Feminization syndrome.
- As a tumor marker of the ovary.
- The various estrogen types’ formation and their effect in different conditions.
- The ovary produces it in small quantities.
- It is produced directly from androstenedione, mostly in the peripheral tissues.
- The plasma estrone level is an indicator of estradiol production because this is an end product of estradiol metabolism.
- This is the major hormone after menopause.
- The metabolism of estradiol or estrone forms Estriol in nonpregnant women.
- Estriol is the major hormone in pregnant women.
- Estriol has no hormonal activity.
- It is produced in large quantities in the last trimester of pregnancy by the placental conversion of the fetal adrenal steroids, synthesized by DHEA derived from the fetal adrenal glands.
- In pregnancy, it is formed by the placental tissue and is a major component.
- Estriol E3 is produced from the placenta from the estrogen precursors. The placenta may produce some estradiol.
- Excretion of Estriol E3 in pregnancy increases around the 8th week of gestation and continues to rise shortly before the delivery.
- Significance of Estriol (E3):
- Serial urine and blood estriol estimation assess placental function and fetal maturity in high-risk pregnancy.
- The concentration of unconjugated E3 in the third pregnancy is from 5 to 40 ng/mL, while the total E3 is 40 to 500 ng/mL.
- This estimation on three occasions gives the idea about fetal well-being.
- It tells fetal well-being means placenta-fetus-viability.
- A sudden drop in the level of estriol in the last trimester of the pregnancy is a signal for fetal-placental abnormality.
- The measurement of secreted estriol is important for fetal well-being.
- Decreasing values indicate fetoplacental deterioration.
- Serial studies usually start at 28 to 30 weeks of gestation and are repeated weekly.
- E3 values are taken for three consecutive days at the same time. If there is a decrease of more than 30%, then there is a possibility of danger to the fetus.
- The value of unconjugated E3 is more reliable than the total E3.
- Follicular phase:
- A rapid rise in estrogen occurs immediately before ovulation and appears to stimulate LH secretion from the anterior pituitary glands.
- The ovarian follicle grows and produces estrogens.
- Ovulatory phase:
- It is just before ovulation; there is a dramatic increase in estrogen.
- Ovulation makes the beginning of the luteal or secretory phase.
- The ovarian follicle transforms into the corpus luteum.
- LH from the anterior pituitary glands stimulates the corpus luteum to secrete progesterone, which will lead o the secretory phase.
- If conception occurs, then nutrient-laden endometrium is ready for implantation.
- This increased estrogen will trigger the hypothalamus and gives LH a surge.
- LH surge is a good indicator of ovulation. This occurs 24 to 36 hours before the ovulation and peaks 10 to 12 hours before the ovulation.
- The luteal phase:
- It is the last half of the menstrual cycle when there is increased production of progesterone and estrogen from the corpus luteum.
- The menstrual phase:
- It is without estrogen, and progesterone endometrium enters the ischemic phase of the menstrual phase.
- This makes the beginning of another cycle.
- The menopausal phase:
- It is when the ovary cannot produce enough amount of estrogen.
- Estradiol is the most active of endogenous estrogens.
- This test is of value with an evaluation of other gonadotropins for in evaluating menstrual and fertility problems in adult females.
- Measurement is also helpful in evaluating gynecomastia or feminization states in estrogen-producing tumors.
- This also helps in evaluating menstrual irregularities and sexual maturity in females.
Normal values of various estrogen
Estradiol E2 (Unconjugated)
|Serum (Blood) pg/ mL||Urine mcg /24 hours|
|Adult male||10 to 50||0 to 6|
|Early Follicular phase||20 to 150|
|Late Follicular phase||40 to 350||1 to 13|
|Mid-cycle phase peak||150 to 750||4 to 14|
|Luteal phase||30 to 450||1 to 17|
|Postmenopausal||≤20||0 to 4|
|Children under 10 years||<15||0 to 6|
Estriol E 3 (Free, unconjugated)
|34 weeks of pregnancy||5.3 to 18.3|
|36 weeks of pregnancy||8.2 to 28.1|
|38 weeks of gestation||8.6 to 38.0|
|39 weeks of pregnancy||7.2 to 34.3|
|40 weeks of pregnancy||9.6 to 28.9|
Estriol E3 Total
|28 to 30 weeks of pregnancy||38 to 140|
|34 weeks of pregnancy||45 to 260|
|36 weeks of pregnancy||48 to 350|
|38 weeks of pregnancy||59 to 570|
|40 weeks of pregnancy||95 to 460|
|Adult male||1.5 to 6.5|
|Early follicular phase||1.5 to 15|
|Late follicular phase||10 to 20|
|Luteal phase||1.5 to 2|
|Postmenopausal||1.5 to 5.5|
|Adult male||20 to 80|
|Follicular phase||60 to 200|
|Luteal phase||160 to 400|
- 28 weeks of gestation in normal pregnancy = average 4 mg/day (range 2 to 7 mg/day).
- 32 weeks of gestation in normal pregnancy = 13 mg/day.
- 36 weeks of gestation in normal pregnancy = 18 mg/day.
- 40 weeks of gestation of normal pregnancy = 26 mg/day
Total estrogen serum = Estradiol + Estrone + Estriol.
The increased level is seen in the following:
- Estrogen-producing tumors.
- Hepatic cirrhosis.
- Liver necrosis.
- Ovarian tumors.
- Precocious puberty.
- Testicular tumor.
- Adrenal tumors.
- Normal pregnancy ( E3 mainly ).
The decreased level is seen in the following:
- Primary and secondary hypogonadism.
- Turner’s syndrome.
- Ovarian agenesis.
- Primary and secondary hypogonadism.
- Stein-Leventhal syndrome.
Question 1: Which estrogen is biologically inactive?
Estriol E3 is biologically inactive.
Question 2: Which estrogen is biologically active?
Estradiol E2 is biologically active.
Excellent summary of Estrogen. Very Very useful.
Thanks a lot for your encouraging remarks.