Estrogens = Estrone E1, Estradiol E2, Estriol E3

Sample
- It is done on the serum of the patient which is separated immediately.
- Can store at 2 to 8 °C for 2 days in a glass test tube.
- Get the time of the sample with reference to the menstrual cycle.
Indication
- 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 to assess fetal health.
- This can be done as a tumor marker in the hormone, estrogen-producing tumors.
Pathophysiology
- Estrogens are the sex hormone responsible for:
- 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 lake the 21-hydroxylase and 11β-hydroxylase, so it can not produce glucocorticoids and, mineralocorticoids like the adrenal cortex.
- Human ovaries produce sex steroids, estrogen, progesterone, and androgens.
- Estrogen’s main site for the inactivation is the liver.
- The main biochemical reactions are hydroxylation, oxidation, and methylation.
- Estrogen source:
- The main source of estrogen in pregnant women is the placenta and it is in mg. This is mainly the estriol.
- The main source in non-pregnant women is the ovary and it is 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 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.
- Testes.
- Estradiol and progesterone are the main secretory products of the ovary.
- More than 20 estrogens are identified but only three have clinical significance and are:
- Estrone (E1).
- Estradiol (E2).
- Estriol (E3).
Estradiol E2
-
It is a more potent hormone and predominantly produced in the ovary.
- E2 is produced exclusively by the ovary, its measurement is often considered sufficient to evaluate the ovarian function.
-
The low level of estradiol 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 have 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 specifically mainly bound to sex hormone-binding globulins (SHBG).
- Nonspecifically bound to albumin.
- SHBG increases by the estrogens, so these are higher in the female than male.
- Estradiol E2 is estimated to evaluate:
- Menstrual and fertility problems.
- Menopausal status.
- Gynecomastia.
- Sexual maturity.
- Feminization syndrome.
- As tumor marker of the ovary.
Estrone E1
- It is produced by the ovary.
- The plasma estrone level is an indicator of estradiol production because this is an end product of the estradiol metabolism.
- This is the major hormone after menopause.
Estriol E3
- 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.
- Estriol E3 is produced from the placenta from the estrogen precursors.
- Excretion of the Estriol E3 in pregnancy increases around the 8th week of gestation and continues to rise shortly before the delivery.
- Serial urine and blood estriol estimation provide an assessment of placental function and fetal maturity in high-risk pregnancy.
- 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 the fetal-placental abnormality.
- The measurement of secreted estriol is important for fetal well-being.
- Decreasing values indicates fetoplacental deterioration.
- Serial studies are started usually at 28 to 30 weeks of gestation and repeated weekly.
- E3 values are taken at 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.
Menstrual cycle
- Follicular phase a rapid rise in estrogens occurs immediately before ovulation and appears to stimulate LH secretion.
- The ovarian follicle grows and produces estrogens.
- Just before ovulation, there is a dramatic increase in estrogen.
- This increased estrogen will trigger the hypothalamus and gives LH 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 is the last half of the menstrual cycle where there is increased production of progesterone and estrogen from the corpus luteum.
- The menopausal phase 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 the evaluation of gynecomastia or feminization states in estrogen-producing tumors.
- This also helps in evaluating menstrual irregularities and sexual maturity in females.
Normal values
Source 2
Estradiol E2 (Unconjugated)
Serum (Blood) pg/ mL | Urine mcg /24 hours | |
Adult male | 10 to 50 | 0 to 6 |
Adult female | ||
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 |
Child under 10 years | <15 | 0 to 6 |
Estriol E 3 (Free, unconjugated) |
ng/mL |
Adult male | <2.0 |
Nonpregnant female | <2.0 |
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 |
Estrone E1 |
|
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 |
Estrogens Total |
pg/mL |
Adult male | 20 to 80 |
Follicular phase | 60 to 200 |
Luteal phase | 160 to 400 |
Postmenopausal | <130 |
Urinary E3
- 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
The increased level is seen in:
- Estrogen producing tumors.
- Gynecomastia.
- Hepatic cirrhosis.
- Liver necrosis.
- Hyperthyroidism.
- Ovarian tumors.
- Precocious puberty.
- Testicular tumor.
- Adrenal tumors.
- Normal pregnancy ( E3 mainly ).
The decreased level is seen in:
- primary and secondary hypogonadism.
- Turner’s syndrome.
- Ovarian agenesis.
- Hypopituitarism.
- Primary and secondary hypogonadism.
- Stein-Leventhal syndrome.
- Menopause.