From the Guidelines
Elevated testosterone and estradiol in a 33-year-old male receiving testosterone replacement therapy can cause several side effects, including acne, oily skin, fluid retention, breast enlargement, mood swings, and increased risk of polycythemia, as supported by the study published in the New England Journal of Medicine 1.
Potential Side Effects
The potential side effects of elevated testosterone and estradiol in this patient may include:
- Acne and oily skin
- Fluid retention
- Breast enlargement (gynecomastia)
- Mood swings and irritability
- Increased aggression
- Decreased testicular size and reduced sperm production, potentially leading to infertility, as noted in the study by Rhoden and Morgentaler 1
- Feminizing effects due to high estradiol, such as breast tissue development and emotional changes
- Cardiovascular risks, including elevated blood pressure, unfavorable cholesterol changes, and potentially higher risk of blood clots or stroke
- Worsening of sleep apnea
- Increased risk of polycythemia (high red blood cell count), which is a common side effect of testosterone injections, as reported by Dobs et al. 1
Management of Side Effects
To manage these side effects, the testosterone dosage should be adjusted to achieve levels within the normal physiological range, and an aromatase inhibitor like anastrozole might be prescribed to reduce estradiol conversion. Regular blood work monitoring is essential, including complete blood count, lipid panel, liver function tests, and hormone levels, as recommended by the American College of Physicians 1.
Hormonal Balance
These side effects occur because excess testosterone can convert to estradiol through aromatization, and both hormones at supraphysiological levels disrupt the body's normal hormonal balance. Therefore, it is crucial to monitor hormone levels closely and adjust treatment accordingly to minimize the risk of adverse effects.
From the FDA Drug Label
ADVERSE REACTIONS The following adverse reactions in the male have occurred with some androgens: Endocrine and urogenital: Gynecomastia and excessive frequency and duration of penile erections. The side effects of elevated testosterone, free and total, plus elevated estradiol in a male receiving hormone replacement testosterone injections may include:
- Gynecomastia
- Excessive frequency and duration of penile erections 2
From the Research
Elevated Testosterone and Estradiol Side Effects
Elevated testosterone, free and total, plus elevated estradiol in a male receiving hormone replacement testosterone injections can cause several side effects. Some of the possible side effects include:
- Gynecomastia, which is the enlargement of breast tissue in men 3
- Hyperestrogenism, which can be harmful to male sexuality 4
- Changes in libido, although high estradiol levels were not associated with higher rates of low libido in one study 4
- Thyroid dysfunction, which can be associated with lower testosterone:estradiol ratios 5
Management of Elevated Estradiol
To manage elevated estradiol levels, aromatase inhibitors such as anastrozole can be used 6, 3, 7. These inhibitors can help reduce estradiol levels and maintain therapeutic testosterone levels. In one study, anastrozole was found to be effective in reducing estradiol levels and sustaining therapeutic testosterone levels in hypogonadal men undergoing testosterone pellet insertion 7.
Testosterone:Estradiol Ratio
The testosterone:estradiol ratio is an important consideration in hormone replacement therapy. A range of 10 to 30 is considered beneficial, with higher values associated with improved spermatogenesis and reduced bone density, and lower values associated with thyroid dysfunction 5. However, further research is needed to determine the optimal value and to clarify measurement strategies and outcome measures related to the testosterone:estradiol ratio.