What are the risks of testosterone therapy in a patient with low estrogen levels?

Risks of Testosterone Therapy in Patients with Low Estrogen Levels

Testosterone therapy in patients with low estrogen levels carries several potential risks including cardiovascular events, erythrocytosis, fluid retention, and prostate-related complications, though the current evidence suggests testosterone therapy is generally safe when properly monitored and dosed appropriately.

Cardiovascular Risks

• The relationship between testosterone therapy and cardiovascular risk remains controversial:
  • Current evidence suggests testosterone therapy is noninferior to placebo regarding major adverse cardiovascular events in men with hypogonadism and preexisting or high risk of cardiovascular disease 1
  • The American Urological Association (AUA) recommends counseling patients that it cannot be stated definitively whether testosterone therapy increases or decreases cardiovascular events 2
  • Untreated low testosterone levels are associated with increased risk of major adverse cardiovascular events 2
  • A higher incidence of atrial fibrillation has been observed in patients receiving testosterone therapy 1

Prostate-Related Risks

• The AUA provides clear guidance regarding prostate health:
  • Clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer 2
  • For patients with a history of prostate cancer, there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy 2
  • Caution is recommended when considering testosterone therapy in men with in-situ prostate cancer on active surveillance or previously treated prostate cancer 2
  • Regular PSA monitoring is recommended on the same schedule as men without testosterone deficiency 2

Hematologic and Other Risks

• Erythrocytosis is a common side effect:

  • Risk varies by administration route: 3-18% with transdermal administration, up to 44% with injections 2
  • Regular monitoring of hematocrit is required 2

• Other potential risks include:

  • Fluid retention (rarely of clinical significance) 2
  • Sleep apnea (infrequent) 2
  • Gynecomastia (rare, usually reversible) 2
  • Skin reactions (varies by administration method) 2
  • Testicular atrophy or infertility (common, especially in young men; usually reversible) 2

Estrogen Levels During Testosterone Therapy

• Contrary to common belief, testosterone therapy does not necessarily lead to elevated estrogen levels:
  • In a study of transgender men, testosterone therapy actually led to a significant decrease in estradiol levels, which remained within the normal male range even after 6 years of follow-up 3
  • In a study of 34,016 men at Low T Centers, approximately 20.2% had high estradiol levels after testosterone therapy 4
  • High estradiol levels were not associated with higher rates of low libido; in fact, normal or lower estradiol levels were associated with higher rates of documented low libido 4

Monitoring Recommendations

• Before initiating treatment:

  • Counsel patients about potential risks and benefits 2
  • Discuss lifestyle modifications (weight loss, increased physical activity) as these can increase testosterone levels naturally 2

• During treatment:

  • Adjust testosterone therapy dosing to achieve total testosterone levels in the middle tertile of the normal reference range (450-600 ng/dL) 2
  • Monitor PSA levels regularly 2
  • Monitor hematocrit to detect erythrocytosis 2
  • Monitor for cardiovascular symptoms (chest pain, shortness of breath, dizziness) 2

Special Considerations

• For patients with low estrogen specifically:
  • There is limited evidence directly addressing testosterone therapy in patients with confirmed low estrogen levels
  • Testosterone is naturally converted to estrogen in adipose tissue through aromatization 4
  • Practitioners sometimes use aromatase inhibitors to treat symptoms of hyperestrogenism, though this practice is not well-supported by evidence 4

Conclusion

While testosterone therapy carries certain risks, proper patient selection, appropriate dosing, and regular monitoring can minimize these risks. The decision to initiate testosterone therapy in patients with low estrogen should be based on a thorough assessment of potential benefits versus risks, with particular attention to cardiovascular and prostate health.