Risks of Testosterone Replacement Therapy in Heavy Smokers

Cardiovascular Risks

The American Heart Association recommends that heavy smokers undergoing testosterone replacement therapy (TRT) should be aware of the increased risks of myocardial infarction and all-cause mortality compared to nonsmokers, with smokers showing a higher risk of cardiovascular events 1

Erythrocytosis (elevated red blood cell count) is a significant risk with TRT, occurring in 3-18% of patients using transdermal formulations and up to 44% of patients receiving injectable testosterone, particularly concerning in smokers who may already have elevated hematocrit levels due to chronic carbon monoxide exposure 1, 2, 3
Monitoring hematocrit/hemoglobin is essential, with temporary discontinuation of TRT or dose reduction recommended if levels rise above the reference range, as recommended by the American Society of Hematology 3

The American Urological Association recommends that all men receiving TRT require careful monitoring for prostate cancer through baseline and follow-up PSA measurements and regular digital rectal examinations 2, 3, 4
Consider prostate biopsy for PSA increases of ≥1.0 ng/mL in one year or if PSA rises above 4.0 ng/mL, as recommended by the National Comprehensive Cancer Network 4

The American Academy of Sleep Medicine recommends that TRT can exacerbate existing sleep apnea or contribute to its development, particularly in men with other risk factors, and assessment for sleep apnea symptoms should be performed before initiating TRT and at follow-up visits 2, 1, 3

The American Heart Association recommends that fluid retention may be problematic, particularly in smokers with compromised cardiovascular function, and low threshold for cardiovascular evaluation is recommended 2, 1, 5
Testicular atrophy and infertility are common due to gonadotropin suppression, as reported by the Endocrine Society 1

The American College of Preventive Medicine recommends that baseline assessment should include cardiovascular risk assessment, PSA and digital rectal examination, hematocrit/hemoglobin, assessment for sleep apnea, and voiding symptoms evaluation 5, 1, 3, 4
Follow-up monitoring should include first follow-up at 1-2 months to assess efficacy, subsequent monitoring every 3-6 months for the first year, then annually, with more frequent monitoring of hematocrit may be warranted in smokers, as recommended by the American Academy of Family Physicians 3, 5, 1

The American Association of Clinical Endocrinologists recommends that oral testosterone preparations should be avoided due to hepatotoxicity risk, and for smokers with cardiovascular concerns, consider easily titratable formulations (gels, patches) rather than long-acting injectables 2, 1, 5
Target testosterone levels should be in the mid-range (350-600 ng/dL) rather than high-normal, particularly in those with cardiovascular risk factors, as recommended by the Endocrine Society 5

Failing to recognize that normalized testosterone levels do not provide the same cardiovascular protection in smokers as in nonsmokers, and inadequate monitoring of hematocrit, which can lead to hyperviscosity and increased thrombotic risk, as reported by the American Heart Association 3, 1
Overlooking the potential exacerbation of sleep apnea, which is already more common in smokers, as recommended by the American Academy of Sleep Medicine 2, 1