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Estrogen = Estrone E1, Estradiol E2, Estriol E3

February 4, 2026Chemical pathologyLab Tests

Table of Contents

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  • Estrogen
        • What sample is needed for Estrogens?
        • What are the indications for estrogen?
      • How will you describe the pathophysiology of estrogen?
    • Estrogen
        • What will be the effect of Estrogen Depletion?
        • What is the source of estrogen secretion?
        • What are the functions of the estrogen hormones?
    • Estradiol (E2)
        • What do you know about estradiol (E2)?
        • How is Estradiol (E2) transported in the blood?
        • How does the estradiol (E2) synthesis take place?
        • What is the significance of Estradiol (E2)?
  • Estrone E1
  • Estriol E3
    • Menstrual cycle
        • How will you define the menstrual cycle?
      • Follicular phase:
      • Ovulatory phase:
      • The luteal phase:
      • The menstrual phase:
      • The menopausal phase:
        • What are the Normal values of various estrogens?
        • Estradiol E2 (Unconjugated)
        • Estriol E 3 (Free, unconjugated)
        • Estriol E3 Total
        • Estrone E1
        • Estrogens Total
        • Urinary E3
        • What are the conditions where estrogens are increased?
        • What are the conditions where estrogens are decreased?
      • Questions and answers:

Estrogen

What sample is needed 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.

What are the indications for estrogen?

  1. Estrogen levels are used 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.

How will you describe the pathophysiology of estrogen?

Estrogen

  1. More than 20 estrogens have been identified, but only three have clinical significance, and these are:
    1. Estrone (E1).
    2. Estradiol (E2). This is predominantly ovarian estrogen.
    3. Estriol (E3).
Classification of Estrogen

Classification of Estrogen

Estrogen derivates formation

Estrogen derivatives formation

  1. Estrogen consists of C18 steroids. At the same time, progesterone is a C21 steroid.
  2. All of these estrogens are derived from androgen precursors such as DHEA and androstenedione. The adrenal cortex, ovaries, and testes synthesize these hormones.
  3. Estrogens are the sex hormones responsible for the following:
    1. The development and maintenance of female sex organs.
    2. Female secondary sex characters.

What will be the effect of Estrogen Depletion?

  1. Loss of bone mineral content.
  2. There are increased stress fractures.
  3. There is postmenopausal osteoporosis.

What is the source of estrogen secretion?

  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, at a µg level. This is mainly estradiol.
  3. Ovarian Follicles.
  4. Corpus luteum from the ovary.
  5. Placenta during pregnancy.
  6. A minute amount is produced from:
    1. Adrenal glands.
    2. Testes.
  7. Estradiol and progesterone are the main secretory products of the ovary.
Estradiol derivatives and their functions

Estradiol derivatives and their functions

What are the functions of the estrogen hormones?

  1. It develops and maintains the female sex organs.
  2. It develops secondary sex characteristics.
  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.
Estrogen hormone functions

Estrogen hormone function

Estradiol (E2)

  1. The most potent estrogen is estradiol (E2), secreted by the ovaries.
  2. Its measurement is sufficient to evaluate ovarian function.
  3. Ovaries lack 21-hydroxylase and 11-β-hydroxylase, so they can not produce glucocorticoids and mineralocorticoids like the adrenal cortex.
  4. Human ovaries produce sex steroids, estrogen, progesterone, and androgens.
  5. Estrogen’s main site for inactivation is in the liver.
  6. The main biochemical reactions are hydroxylation, oxidation, and methylation.

What do you know about 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.
  2. E2 is produced exclusively by the ovary; its measurement is often considered sufficient to evaluate ovarian function.
  3. Low estradiol levels stimulate the hypothalamus to release gonadotropin-releasing hormone.
  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.

How is Estradiol (E2) transported in the 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 with the estrogens, so these are higher in females than in males.

How does the estradiol (E2) synthesis take place?

Estradiol (E2) synthesis

Estradiol (E2) synthesis

What is the significance of Estradiol (E2)?

  1. Menstrual and fertility problems.
  2. Menopausal status.
  3. Gynecomastia.
  4. Sexual maturity.
  5. Feminization syndrome.
  6. As a tumor marker of the ovary.

Estrone E1

  1. The ovary produces 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.
  3.  Estriol has no hormonal activity.
  4. 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.
  5. In pregnancy, it is formed by the placental tissue and is a major component.
  6. Estriol E3 is produced by the placenta from the estrogen precursors. The placenta may produce some estradiol.
  7. Excretion of Estriol E3 in pregnancy increases around the 8th week of gestation and continues to rise shortly before delivery.

What is the significance of Estriol (E3)?

  1. Serial urine and blood estriol estimation assesses placental function and fetal maturity in high-risk pregnancy.
  2. 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.
    1. This estimate, based on three occasions, provides an idea of fetal well-being.
  3. It tells fetal well-being means placenta-fetus-viability.
  4. A sudden drop in the level of estriol in the last trimester of the pregnancy is a signal for fetal-placental abnormality.
Placental hormones

Placental hormones

  1. Measuring secreted estriol is important for understanding the estrogen pathway and its derivatives.
  2. Decreasing values indicate fetoplacental deterioration.
  3. 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 placenta

Estriol E3 from the placenta

Estradiol and Estriol (E2, E3) sources

Estradiol and Estriol (E2, E3) sources

Menstrual cycle

How will you define the menstrual cycle?

  1. A menstrual cycle begins when a woman has her period. or menstruate.
  2. This is the monthly shedding of the uterus lining.
  3. Menstrual blood is partly blood and partly tissue from the inside of the uterus.
  4. It enters from the uterus to the cervix and is then excreted from the vagina.
  5. Menstruation depends on hormones from the pituitary glands and, to some extent, on hormones from the ovaries.
  6. Menstruation prepares the uterus for the implantation of a fertilized ovum.
  7. The menstrual cycle varies from 21 to 35 days, and it is still considered normal.
  8. This bleeding phase lasts 3 to 7 days. But most ladies have three days of bleeding.
Menstrual cycle summary

Menstrual cycle summary

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.

Ovulatory phase:

  1. It is just before ovulation, when estrogen levels increase dramatically.
  2. Ovulation is 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 to the secretory phase.
  5. If conception occurs, then the nutrient-laden endometrium is ready for implantation.
  6. This increased estrogen will trigger the hypothalamus and cause a surge of LH.
  7. 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.
Menstrual cycle hormones

Menstrual cycle hormones

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.

The menstrual phase:

  1. Without estrogen and progesterone, the endometrium enters the ischemic phase of the menstrual phase.
  2. This makes the beginning of another cycle.
Menstrual cycle changes and hormones

Menstrual cycle changes and hormones

The menopausal phase:

  1. It occurs when the ovary cannot produce enough estrogen.
  2. Estradiol is the most active of endogenous estrogens.
  3. This test is of value in evaluating other gonadotropins for menstrual and fertility problems in adult females.
  4. Measurement is also helpful in evaluating gynecomastia or feminization states in estrogen-producing tumors.
  5. This also helps in evaluating menstrual irregularities and sexual maturity in females.

What are the Normal values of various estrogens?

Source 2

Estradiol E2 (Unconjugated)

Sex 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
Children under 10 years <15 0 to 6

Another source

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 (132 to 485 nmol/L)
34 weeks of pregnancy 45 to 260 (156 to 901 nmol/L)
36 weeks of pregnancy 48 to 350(159 to 277 nmol/L)
38 weeks of pregnancy 59 to 570 (214 to 1976 nmol/L)
40 weeks of pregnancy 95 to 460 (306 to 1595 nmol/L)

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

  1. 28 weeks of gestation in a 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 a normal pregnancy = 26 mg/day

Total serum estrogen = Estradiol + Estrone + Estriol.

What are the conditions where estrogens are increased?

  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 ).

What are the conditions where estrogens are decreased?

  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.

Questions and answers:

Question 1: Which estrogen is biologically inactive?
Show answer
Estriol E3 is biologically inactive.
Question 2: Which estrogen is biologically active?
Show answer
Estradiol E2 is biologically active.

Possible References Used
Go Back to Chemical pathology

Comments

Mehboob Fatteh Reply
January 29, 2022

Excellent summary of Estrogen. Very Very useful.
Mehboob Fatteh

Dr. Riaz Reply
January 30, 2022

Thanks a lot for your encouraging remarks.

Ahmet Keyan Reply
May 26, 2022

Thank you Doctor. The best respect

Dr. Riaz Reply
May 26, 2022

Thanks.

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