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Estradiol (E2)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Primary Estrogen – Marker for Ovarian Function, Fertility, Menopause & Hormonal Disorders)

Synonyms

  • Estradiol
  • 17β-Estradiol
  • E2
  • Estrogen hormone
  • Ovarian estrogen
  • Follicular estrogen

Units of Measurement

  • pmol/L
  • pg/mL
  • pg/dL
  • pg/100 mL
  • pg%
  • pg/L
  • ng/L

1 pg/mL = 3.671 pmol/L
1 pg/mL = 100 pg/dL
1 pg/mL = 1000 pg/L
pg/dL = pg% = pg/100 mL

Description

Estradiol (E2) is the most biologically potent estrogen in humans.
It is produced mainly by the ovaries, with minor contributions from:

  • Adrenal glands
  • Testes
  • Peripheral conversion of androgens (fat tissue)

E2 regulates:

  • Menstrual cycle
  • Ovulation
  • Secondary sexual characteristics
  • Bone metabolism
  • Cardiovascular function
  • Mood and cognition

Estradiol is essential in assessing:

  • Fertility
  • Puberty
  • Menopause
  • Polycystic ovary syndrome (PCOS)
  • Hypogonadism
  • Tumor-related hormonal changes

Physiological Role

Major functions include:

  • Follicular growth
  • Endometrial proliferation
  • Bone density maintenance
  • Lipid metabolism
  • Vaginal & breast tissue development
  • Feedback regulation of GnRH, LH, and FSH

Clinical Significance

Low Estradiol Levels

Seen in:

1. Menopause / Premature Ovarian Failure

  • Hot flashes
  • Vaginal dryness
  • Osteoporosis risk

2. Hypogonadism

  • Turner syndrome
  • Hypothalamic amenorrhea
  • Pituitary insufficiency
  • Chronic illness or extreme stress

3. Poor Ovarian Reserve

  • Infertility
  • Low AMH, low antral follicle count

4. Anorexia / Malnutrition

  • Low body fat reduces aromatization

High Estradiol Levels

1. Ovarian Hyperstimulation / Ovulation Induction

  • During IVF
  • Risk of OHSS when very high

2. Estrogen-Secreting Tumors

  • Granulosa cell tumor
  • Sertoli-Leydig tumors

3. PCOS

  • Mild–moderate elevation
  • Altered LH/FSH ratio

4. Pregnancy

  • Estradiol increases progressively
  • Placenta becomes major source

5. Liver Disease

  • Reduced estrogen metabolism

6. Gynecomastia in Men

  • Increased aromatization
  • Testicular tumors
  • Medications (spironolactone, HRT)

Reference Intervals

(Tietz 8E + Endocrine Society + ASRM + Mayo + ARUP)
Estradiol varies strongly with sex, age, and menstrual cycle phase.

Women (pg/mL)

Follicular Phase:

  • 20 – 150 pg/mL

Mid-Cycle Peak (Ovulation):

  • 150 – 750 pg/mL

Luteal Phase:

  • 30 – 450 pg/mL

Postmenopause:

  • < 10 – 30 pg/mL

Men

  • 10 – 40 pg/mL

Children

  • Prepubertal: <10 pg/mL
  • Early puberty: 10–50 pg/mL
  • Late puberty: 20–200 pg/mL

Diagnostic Uses

1. Menstrual Cycle & Ovulation Assessment

  • Detects follicular maturity
  • Used in ovulation induction cycles
  • Assesses response in fertility treatments

2. Infertility Workup

  • Estradiol + AMH + AFC → ovarian reserve
  • High E2 → PCOS
  • Low E2 → ovarian insufficiency

3. Pubertal Disorders

  • Precocious puberty
  • Delayed puberty
  • Gonadal failure

4. Menopause Diagnosis

Low E2 + high FSH confirms ovarian failure.

5. Tumor Marker

For:

  • Granulosa cell tumors
  • Feminizing tumors

6. Gynecomastia Evaluation in Men

E2 included in hormonal panel.

7. Endocrine Disorders

Used in:

  • PCOS
  • Hyperprolactinemia
  • Thyroid disorders

Analytical Notes

  • Serum sample
  • Diurnal variation minimal compared to progesterone
  • Cycle-day specificity important
  • Immunoassays often imprecise at very low levels
  • LC-MS/MS preferred for male, pediatric & postmenopausal levels
  • Biotin supplements may cause assay interference

Clinical Pearls

  • Estradiol peaks just before ovulation (~200–400 pg/mL).
  • In IVF, E2 > 3000 pg/mL indicates risk of OHSS.
  • Anestrous estradiol <10 pg/mL defines menopause biochemically.
  • High estradiol in men warrants evaluation for testicular tumors or liver disease.
  • Estradiol must always be interpreted with FSH, LH, and progesterone.

Interesting Fact

Estradiol is so potent that 1 mg of estradiol contains more biological activity than grams of other steroids, making it one of the most powerful endogenous hormones.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Steroid Hormones.
  2. Endocrine Society Guidelines - Female Hormone Testing.
  3. ASRM Reproductive Endocrinology Standards.
  4. AACE/ACE Hormone Evaluation Guidelines.
  5. Mayo Clinic Laboratories - Estradiol.
  6. ARUP Consult - Estradiol Interpretation.
  7. MedlinePlus / NIH - Estradiol Test.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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