General Health

Estrogen (E1, E2, E3, E4)

Author:

Shaun Ward BSc, MSc
on
May 19, 2024
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Take-home points
  • Men produce small amounts of estrogen to maintain overall health.
  • Estradiol is the most common and strongest form of estrogen in men.
  • Abnormal estrogen levels in men can be a cause or symptom of low testosterone levels, sexual dysfunction, impaired bone health and gynecomastia.
  • Although rare, testosterone replacement therapy (TRT) may lead to elevated estrogen levels, which may need to be controlled.  

What is estrogen and what does it do in men?

Estrogen is a group of naturally-occurring hormones responsible for developing and regulating the reproductive system. Three hormones, to be exact. These were originally called “female hormones” and continue to take centre stage in discussions of women’s health, with key roles in ovulation and the menstrual cycle. In men’s health, not so much; estrogen often hides in the shadows of testosterone when testicles are involved. But men of all ages still produce—or, should produce—small amounts of estrogen.

Men produce most of their estrogen from the conversion of testosterone via an enzyme called aromatase. Some amount is also made directly by fat tissue, the brain and the walls of blood vessels. What is the role of estrogen in men, you ask? To aid the production of sperm and to remain fertile. Other roles include supporting growth, sexual maturation, the metabolism of fats, and possibly functioning as part of the cardiovascular system.1

What are the four types of estrogen?

The three major types of naturally-occurring estrogens are:

  • Estrone (E1): This estrogen is mostly derived from another estrogen, estradiol, and is produced in fat cells and the adrenal glands.  
  • Estradiol (E2): This estrogen is usually made from cholesterol in the testicles, and is the strongest of the naturally-occurring estrogens.  
  • Estriol (E3): This estrogen is weakest and men produce minimal amounts. The placenta usually produces estriol during pregnancy.  

Technically, there is a fourth estrogen called oestetrol (E4), but it is produced exclusively during pregnancy by the fetal liver and is not present in men under normal circumstances.

What are normal estrogen levels in men?

In adult men, normal estrogen levels typically range from 1080 picograms per millilitre (pg/mL).2,3 Of this, 10–40 pg/mL is estradiol. These levels may vary slightly depending on age, health status and individual factors. For example, it is normal for estrogen levels to be extremely low in teenagers and adolescents, perhaps undetectable in many instances. Whereas more testosterone is converted to estrogen in older men, their estrogen levels tend to be higher.

What do high and low estrogen levels indicate in men?  

High estrogen levels (hyperestrogenism) in men can indicate: 4,5,6,7

  • Decreased libido
  • Low testosterone (hypogonadism)
  • Infertility
  • Erectile dysfunction
  • Gynecomastia (enlargement of breast tissue)  

Conversely, low estrogen levels in men can indicate: 8,9,10,11,12  

  • Decreased bone density
  • Low testosterone (hypogonadism)
  • Delayed ejaculation
  • Increased risk of cardiovascular disease

Currently, evidence does not clearly establish the relationship between estrogen and low testosterone levels in men. On the one hand, reduced levels of sex hormones often co-occur; on the other hand, high estrogen levels may be a sign that too much testosterone is being converted to estrogen, thus lowering testosterone levels. More evidence is needed to establish the specifics of this relationship in men.

Does TRT raise estrogen?

Testosterone replacement therapy (TRT) involves administering testosterone to men with low testosterone levels to restore normal levels and alleviate related symptoms. However, in rare cases, TRT can lead to increased estrogen levels due to excess conversion of testosterone to estradiol by the aromatase enzyme.  

A review of estrogens in men stated that “During testosterone replacement, estrogens may rise and occasionally reach elevated levels”.13 In a study of 34,000 men with low testosterone, 50% were taking TRT, and 20.2% had high levels of estradiol.14 Raised estrogen levels have become a relatively common explanation for a couple of TRT’s side effects, gynecomastia and water retention. To mitigate the risk of elevated estrogen levels during TRT, healthcare providers may start with a low dose of testosterone to assess a patient’s response and/or prescribe aromatase inhibitors alongside TRT to prevent excessive estrogen conversion.  

References
  1. Cooke PS et al. Physiol Rev 2017;97(3):995–1043.
  2. Yamamoto M et al. Int J Urol 1995;2(1):44–46.
  3. Chadid S et al. J Endrocr Soc 2019;3(10):1825–1836.
  4. Martin RM et al. J Clin Endrocrinol Metab 2003;88(7):3027–3024.
  5. Valenta LJ & Elias AN. N Engl J Med 1986;314(3):186.
  6. Sansone A et al. Endocrine 2017;55(1):37–44.
  7. Belladelli F et al. Andrology 2024;12(1):179–185.
  8. Chen T et al. Sci Rep 2020;10:12660.
  9. Appiah D et al. Atherosclerosis 2022;361:34–40.
  10. Komesaroff PA et al. Hypertension 2001;38(5):1011–1016.
  11. Trabao S et al. Fertil Steril 2011;95(7):2324–2329.
  12. Amin S et al. Ann Intern Med 2000;133(12):951–963.
  13. Kacker R et al. J Sex Med 2012;9(6):1681–1696.
  14. Tan RS et al. Am J Mens Health 2015;9(3):229–234.

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