Hormone Biomarkers: Estradiol in Women

Optimal Takeaways

Estradiol is the most potent form of circulating estrogen with effects in both females and males. At desirable levels, estradiol supports bone integrity, growth hormone regulation, glucose metabolism, and modulation of unpleasant vasomotor symptoms. 

Low levels in women are associated with menopause, inhibition of aromatase enzyme, pregnancy failure, low pituitary function, and anorexia nervosa. High levels are associated with pregnancy, ovulation induction, post-menopausal breast cancer, estrogen-secreting tumors, adrenal tumors, hyperthyroidism, and liver cirrhosis and necrosis.

Standard Ranges (Immunoassay)

• Follicular Phase: 19-144 pg/mL (69.75 – 528.62 pmol/L)
• Mid-Cycle: 64-357 pg/mL (234.94 – 1310.55 pmol/L)
• Luteal Phase: 56-214 pg/mL (205.58 – 785.59 pmol/L)
• Postmenopausal: ≤31 pg/mL (113.80 pmol/L)

Low levels of estradiol in females can be seen with menopause and aromatase inhibitor therapy (Ketha 2015). Low levels can also be seen with failing pregnancy, Turner syndrome, hypopituitarism, anorexia nervosa (Pagana 2021), and post-menopausal hot flashes (Hariri 2021).

High levels of estradiol in females may be seen with pregnancy, induction of ovulation, postmenopausal breast cancer risk (Ketha 2015), and estrogen-secreting tumors (Rosner 2013). Elevated levels may also be seen with adrenal tumors, hyperthyroidism, liver cirrhosis, and liver necrosis (Pagana 2021).

Overview

Estrogen is found in different forms in the body with estrone (E1), estradiol (E2), and estriol (E3) constituting the three major forms. Estradiol (E2) is the most potent circulating estrogen with effects in females and males. It influences sexual health and reproduction and has beneficial effects on bone metabolism, cardiovascular health, and nervous system function at physiological levels. However, it can be detrimental in excess, including chronic low-dose exposure to endocrine disrupting chemicals (MohanKumar 2018).

Estradiol can be synthesized via aromatase conversion from testosterone, or ovarian synthesis from estrone (Hariri 2021). Estradiol is more than a sex hormone as it affects several tissues throughout the body including adipose tissue, blood vessels, brain, bone, muscle, gastrointestinal tract, liver, kidney, lung, pancreas, and skin. Estradiol also affects coagulation (Rosner 2013).

Estradiol is more than a sex hormone as it affects several tissues throughout the body including adipose tissue, blood vessels, the brain, bone, muscle, gastrointestinal tract, liver, kidney, lung, pancreas, and skin. Estradiol also affects coagulation (Rosner 2013).

Levels peak during the ovulatory phase in menstruating women but may be monitored throughout the lifespan to assist in the assessment of fertility, ovarian tumors, and menopausal status (Pagana 2021). Monitoring may also be carried out in amenorrhea, PCOS, hirsutism, and aromatase inhibitor therapy. Levels may be decreased as low as 1-5 pg/mL (3.67-18.36) during aromatase inhibitor therapy for breast cancer (Ketha 2015).

Circulating estradiol in menstruating women can range from 30-800 pg/mL (110-2937 pmol/L), and 10-100 pg/mL (73-367 pmol/L) in postmenopause hormone replacement. Levels can reach levels as high as 10,000 pg/mL (36,710 pmol/L) in ovarian stimulation treatment, and 20,000 pg/mL (73,420 pmol/L) in pregnancy (Stanczyk 2014).

References

Hariri, Lana. and Anis Rehman. “Estradiol.” StatPearls, StatPearls Publishing, 13 February 2021. This book is distributed under the terms of the Creative Commons Attribution 4.0 International License.

Ketha, Hemamalini et al. “Estradiol assays--The path ahead.” Steroids vol. 99,Pt A (2015): 39-44. doi:10.1016/j.steroids.2014.08.009

MohanKumar, Sheba M J et al. “Chronic estradiol exposure - harmful effects on behavior, cardiovascular and reproductive functions.” Reproduction (Cambridge, England) vol. 156,5 (2018): R169-R186. doi:10.1530/REP-18-0116

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Rosner, William et al. “Challenges to the measurement of estradiol: an endocrine society position statement.” The Journal of clinical endocrinology and metabolism vol. 98,4 (2013): 1376-87. doi:10.1210/jc.2012-3780

Stanczyk, Frank Z, and Nigel J Clarke. “Measurement of estradiol--challenges ahead.” The Journal of clinical endocrinology and metabolism vol. 99,1 (2014): 56-8. doi:10.1210/jc.2013-2905