Estrogens

Sample for Estrogens

1. It is done on the patient’s serum, which is separated immediately.
2. It can be stored at 2 to 8 °C for 2 days in a glass test tube.
3. Get a sample regarding the menstrual cycle.

Indications for Estrogens

1. Estrogen level is estimated to assess sexual maturity.
2. To assess menstrual problems.
3. To assess fertility problems.
4. In males to assess the gynecomastia and feminization syndrome.
5. In pregnant women, assess fetal health.
6. This can be done as a tumor marker in the hormone estrogen-producing tumors.

Pathophysiology of Estrogens

Estrogen

1. There are three major estrogens:
   1. Estrone (E1).
   2. Estradiol (E2). This is predominantly ovarian estrogen.
   3. Estriol (E3).
2. Estrogen consists of C18 steroids. At the same time, progesterone is a C21 steroid.
3. All of these estrogens are derived from androgenic precursors like DHEA, and androstenedione. These are synthesized by the adrenal cortex, ovaries, and testis.
4. Estrogens are the sex hormone responsible for the following:
   1. The development and maintenance of female sex organs.
   2. Female secondary sex characters.
5. The most potent estrogen is estradiol E2 secreted by the ovaries. Its measurement is sufficient to evaluate ovarian function.
   1. Ovaries lack 21-hydroxylase and 11-β-hydroxylase, so they can not produce glucocorticoids and mineralocorticoids like the adrenal cortex.
   2. Human ovaries produce sex steroids, estrogen, progesterone, and androgens.
6. Estrogen’s main site for inactivation in the liver.
   1. The main biochemical reactions are hydroxylation, oxidation, and methylation.
7. Estrogen source:
   1. The main source of estrogen in pregnant women is the placenta, which is in mg. This is mainly the estriol.
   2. The main source in non-pregnant women is the ovary in µg quantity. This is mainly estradiol.
8. Functions of the estrogen hormone:
   1. It develops and maintains the female sex organs.
   2. It develops secondary sex characters.
   3. It regulates the menstrual cycle (with the help of progesterone).
   4. Maintain breast and uterus growth.
   5. It maintains pregnancy.
   6. It also helps calcium homeostasis and has a beneficial effect on bone.
   7. It also accelerates linear bone growth and results in epiphyseal closure.
9. Depletion of estrogen for a long time leads to:
   1. Loss of bone mineral contents.
   2. There are increased stress fractures.
   3. There is postmenopausal osteoporosis.

Estrogen hormone functions

10. Estrogens are secreted by:
    1. Ovarian Follicles.
    2. Corpus luteum from the ovary.
    3. Placenta during pregnancy.
    4. A minute amount is produced from:
       1. Adrenal glands.
       2. Testes.

Estrogen hormone sources

11. Estradiol and progesterone are the main secretory products of the ovary.
12. More than 20 estrogens are identified, but only three have clinical significance and these are:
    3. Estrone (E1).
    4. Estradiol (E2).
    5. Estriol (E3).

Estradiol E2

1. It is a more potent hormone and is predominantly produced in the ovary. It exists in a reversible state with estrone.
   1. Estrone has a weaker biological function.
   2. The final product is estriol (E3), a steroid without biological activity.

Components of Estrogen

2. E2 is produced exclusively by the ovary; its measurement is often considered sufficient to evaluate ovarian function.
3. The low estradiol level stimulates the hypothalamus to produce a gonadotropin hormone-releasing factor.
4. These hormones stimulate the pituitary to produce a Follicular stimulating hormone (FSH) and luteinizing hormone (LH).
5. These two hormones (FSH and LH) stimulate the ovary to produce E2, which will provide the peak during the ovulatory phase.
6. Estradiol transport in blood:
   1. 97% of the estradiol E2 in the blood is bound to plasma proteins.
   2. It has a high affinity and is specifically mainly bound to sex hormone-binding globulins (SHBG).
   3. Nonspecifically bound to albumin.
   4. SHBG increases by the estrogens, so these are higher in females than males.

Estradiol synthesis

7. Estradiol E2 significance:
   1. Menstrual and fertility problems.
   2. Menopausal status.
   3. Gynecomastia.
   4. Sexual maturity.
   5. Feminization syndrome.
   6. As a tumor marker of the ovary.
8. The various estrogen types’ formation and their effect in different conditions.

Estrogens: Estrogen and its derivative’s significance

Estrogen derivative formation

Estrone E1

1. The ovary produces it in small quantities.
2. It is produced directly from androstenedione, mostly in the peripheral tissues.
3. The plasma estrone level is an indicator of estradiol production because this is an end product of estradiol metabolism.
4. This is the major hormone after menopause.

Estriol E3

1. The metabolism of estradiol or estrone forms Estriol in nonpregnant women.
2. Estriol is the major hormone in pregnant women.
   1.  Estriol has no hormonal activity.
   2. 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.
   3. In pregnancy, it is formed by the placental tissue and is a major component.
   4. Estriol E3 is produced from the placenta from the estrogen precursors. The placenta may produce some estradiol.
3. Excretion of Estriol E3 in pregnancy increases around the 8th week of gestation and continues to rise shortly before the delivery.
4. Significance of Estriol (E3):
5. Serial urine and blood estriol estimation assess placental function and fetal maturity in high-risk pregnancy.
   1. 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.
   2. This estimation on three occasions gives the idea about fetal well-being.
6. It tells fetal well-being means placenta-fetus-viability.
   1. A sudden drop in the level of estriol in the last trimester of the pregnancy is a signal for fetal-placental abnormality.

Placenta hormones

7. The measurement of secreted estriol is important for fetal well-being.
8. Decreasing values indicate fetoplacental deterioration.
9. Serial studies usually start at 28 to 30 weeks of gestation and are repeated weekly.
   1. 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.
   2. The value of unconjugated E3 is more reliable than the total E3.

Estriol E3 from the placenta

Estradiol E2, and E3 source

Menstrual cycle

1. Follicular phase:
   1. A rapid rise in estrogen occurs immediately before ovulation and appears to stimulate LH secretion from the anterior pituitary glands.
   2. The ovarian follicle grows and produces estrogens.
2. Ovulatory phase:
   1. It is just before ovulation; there is a dramatic increase in estrogen.
   2. Ovulation makes the beginning of the luteal or secretory phase.
   3. The ovarian follicle transforms into the corpus luteum.
   4. LH from the anterior pituitary glands stimulates the corpus luteum to secrete progesterone, which will lead o the secretory phase.
   5. If conception occurs, then nutrient-laden endometrium is ready for implantation.
3. This increased estrogen will trigger the hypothalamus and gives LH a surge.
4. 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.
5. The luteal phase:
   1. It is the last half of the menstrual cycle when there is increased production of progesterone and estrogen from the corpus luteum.
6. The menstrual phase:
   1. It is without estrogen, and progesterone endometrium enters the ischemic phase of the menstrual phase.
   2. This makes the beginning of another cycle.

Menstrual cycle and hormonal changes

10. The menopausal phase:
    10. It is when the ovary cannot produce enough amount of estrogen.
    11. Estradiol is the most active of endogenous estrogens.
    12. This test is of value with an evaluation of other gonadotropins for in evaluating menstrual and fertility problems in adult females.
    13. Measurement is also helpful in evaluating gynecomastia or feminization states in estrogen-producing tumors.
11. This also helps in evaluating menstrual irregularities and sexual maturity in females.

Normal values of various estrogen

Source 2

Estradiol E2 (Unconjugated)

Another source

Urinary E3

1. 28 weeks of gestation in normal pregnancy = average 4 mg/day  (range 2 to 7 mg/day).
2. 32 weeks of gestation in normal pregnancy = 13 mg/day.
3. 36 weeks of gestation in normal pregnancy = 18 mg/day.
4. 40 weeks of gestation of normal pregnancy = 26 mg/day

Total estrogen serum = Estradiol + Estrone + Estriol.

The increased level is seen in the following:

1. Estrogen-producing tumors.
2. Gynecomastia.
3. Hepatic cirrhosis.
4. Liver necrosis.
5. Hyperthyroidism.
6. Ovarian tumors.
7. Precocious puberty.
8. Testicular tumor.
9. Adrenal tumors.
10. Normal pregnancy ( E3 mainly ).

The decreased level is seen in the following:

1. Primary and secondary hypogonadism.
2. Turner’s syndrome.
3. Ovarian agenesis.
4. Hypopituitarism.
5. Primary and secondary hypogonadism.
6. Stein-Leventhal syndrome.
7. Menopause.