From the Guidelines
Elevated estrogen and estradiol levels in males are primarily caused by obesity, which leads to increased aromatization of testosterone to estradiol in adipose tissue, and the workup should include laboratory tests such as total and free testosterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and thyroid function tests, as suggested by recent studies 1. The causes of elevated estrogen and estradiol in males can be multifactorial, including:
- Obesity, which is a common cause due to the conversion of testosterone to estrogen via aromatase enzyme activity in adipose tissue 1
- Liver disease, which reduces estrogen clearance
- Hyperthyroidism, which increases sex hormone-binding globulin, affecting hormone balance
- Certain medications, such as antibiotics, antipsychotics, and hormone therapies, which can raise estrogen levels
- Tumors, which can produce estrogen or stimulate its production
The workup for elevated estrogen and estradiol levels in males should begin with a comprehensive history and physical examination, followed by laboratory tests, including:
- Total and free testosterone
- Estradiol
- Luteinizing hormone (LH)
- Follicle-stimulating hormone (FSH)
- Prolactin
- Thyroid function tests If medication-induced, discontinuation of the offending agent may be recommended. For obesity-related cases, weight loss is advised. Imaging studies such as testicular ultrasound, abdominal CT, or MRI may be necessary if a tumor is suspected. Liver function tests should be performed if liver disease is a concern. Treatment depends on the underlying cause and may include aromatase inhibitors like anastrozole (1mg daily) or exemestane (25mg daily) in some cases, though these should only be used under medical supervision as they can have significant side effects including bone density loss with prolonged use. In patients with obesity, treatment with testosterone-replacement therapy should be considered when the morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments, and the hypogonadism workup has been completed to rule out an etiology of hypogonadism unrelated to obesity, as suggested by 1. The method of testosterone replacement should be individualized for each patient, with transdermal testosterone preparations suggested for most hypogonadal men because they usually produce normal serum testosterone concentrations, and patients typically find them the most convenient 1. After treatment is initiated, patients should be monitored to determine that normal serum testosterone concentrations are being achieved, with testosterone levels tested 2 to 3 months after treatment initiation, and/or after any dose change, as recommended by 1.
From the FDA Drug Label
The growth of many cancers of the breast is stimulated or maintained by estrogens. In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol Anastrozole is a selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone.
The causes of elevated estrogen and estradiol in males are not directly addressed in the provided drug label. However, it can be inferred that aromatase enzyme plays a role in converting androgens to estrogens.
- Possible causes may include:
- Increased activity of the aromatase enzyme
- Elevated levels of androgens (e.g., androstenedione and testosterone) The workup for elevated estrogen and estradiol levels in males is not explicitly stated in the label, but it may involve assessing aromatase enzyme activity and androgen levels 2.
From the Research
Causes of Elevated Estrogen and Estradiol in Males
- Obesity is a significant factor, as seen in a study from 3, where morbidly obese men had 2-fold elevated serum estrone and 17beta-estradiol levels.
- Testosterone replacement therapy, particularly injectable testosterone, can lead to elevated estradiol levels, as noted in 4, where approximately 20% of men treated with injectable testosterone had high estradiol levels.
- Certain medical conditions, such as hypogonadism, can also contribute to elevated estrogen and estradiol levels in males.
Workup for Elevated Estrogen and Estradiol Levels
- Laboratory tests, including serum estradiol and testosterone levels, should be conducted to confirm elevated estrogen and estradiol levels 4.
- A physical examination and medical history should be taken to identify any underlying medical conditions that may be contributing to the elevated hormone levels.
- Imaging studies, such as ultrasound or MRI, may be necessary to rule out any testicular or adrenal abnormalities 5.
Effects of Elevated Estrogen and Estradiol on Male Reproductive Function
- Elevated estrogen and estradiol levels can have negative effects on male reproductive function, including decreased libido, erectile dysfunction, and impaired spermatogenesis 5, 6.
- Estradiol plays a critical role in modulating libido, erectile function, and spermatogenesis in males 5.
- The balance between testosterone and estrogen is essential for maintaining normal male reproductive function, and disruptions to this balance can have significant consequences 7, 6.