Hormone Biomarkers: Estradiol in Men

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, sexual health, and modulation of unpleasant vasomotor symptoms.

Low levels in men may be associated with diabetes, insulin resistance, visceral adiposity, decreased libido, and aging, while elevated levels may be associated with testicular tumors, sexual dysfunction, hypogonadism, and gynecomastia.

Standard Range: 0 - 39 pg/mL (0 - 143.17 pmol/L)

The ODX Range: 24 - 39 pg/mL (88.10 – 143.17 pmol/L)

Low estradiol in men can be seen with type 2 diabetes, low free testosterone, aromatase inhibitor therapy (Russell 2019), visceral adiposity, and insulin resistance (Russell 2017). Low levels are associated with a decrease in libido (Schulster 2016). Elderly men tend to have low estradiol levels (Rosner 2013).

High estradiol in men may increase incidence of erectile dysfunction independently of low testosterone (Schulster 2016). Elevated levels can be seen in gynecomastia, feminization, hypogonadism, testicular tumors, adrenal tumors, hyperthyroidism, and liver cirrhosis and 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 and has effects in both 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 from endocrine disrupting chemicals (MohanKumar 2018).

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).

In males, up to 50% of estradiol is secreted from the testes. The remainder comes from the aromatization of testosterone to estradiol in the periphery including bone, brain, muscle, and adipose tissue. Mounting evidence exploring the role of E2 in males indicates that it plays a role in regulation of the hypothalamic-pituitary-axis and growth hormone-IGF-1 axes, reproductive function, bone growth and maintenance, glucose metabolism, body composition, and vasomotor dilation and constriction of blood vessels. Median serum levels of E2 are maintained at 40.9 pg/mL (150 pmol/L) in healthy young men and 24.5 pg/mL (90 pmol/L) in older healthy men (Russell 2019).

Estradiol in men also contributes to prevention of body fat accumulation, limitation of vasomotor symptoms, and enhancement of sexual function in conjunction with testosterone (Basin 2018). Research indicates that levels of E2 below 10 pg/mL (37 pmol/L) in men were associated with increased risk of bone loss and increased vasomotor symptoms. Maintaining a level above 25 pg/mL (92 pmol/L) helped normalize vasomotor symptoms. Levels of at least 19 pg/mL (70 pmol/L) were needed to improve insulin resistance and prevent increased adiposity (Russel 2017).

Estradiol also has a positive impact on mood due to its effects on serotonin levels and serotonin receptors. Decreased levels that occur during androgen deprivation therapy for prostate cancer are associated with decreased libido (Schulster 2016). Estradiol levels in men are monitored in testicular and prostate cancer as well (Ketha 2015).

References

Bhasin, Shalender et al. “Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.” The Journal of clinical endocrinology and metabolism vol. 103,5 (2018): 1715-1744. doi:10.1210/jc.2018-00229

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

Russell, Nicholas et al. “Estradiol for the mitigation of adverse effects of androgen deprivation therapy.” Endocrine-related cancer vol. 24,8 (2017): R297-R313. doi:10.1530/ERC-17-0153

Russell, Nicholas, and Mathis Grossmann. “MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone.” European journal of endocrinology vol. 181,1 (2019): R23-R43. doi:10.1530/EJE-18-1000

Schulster, Michael et al. “The role of estradiol in male reproductive function.” Asian journal of andrology vol. 18,3 (2016): 435-40. doi:10.4103/1008-682X.173932