What are the risks of testosterone supplementation in an elderly male patient?

Risks of Testosterone Supplementation in Elderly Men

Testosterone replacement therapy in elderly men carries significant cardiovascular risks, erythrocytosis requiring monitoring, and potential prostate concerns, but when appropriately indicated for confirmed hypogonadism with symptoms, the benefits for sexual function may outweigh risks with careful patient selection and monitoring. 1

Cardiovascular Risks

The cardiovascular safety of testosterone therapy remains the most controversial area, with conflicting evidence:

• The FDA mandated labeling changes in 2015 regarding possible increased risk of myocardial infarction and stroke based on post-marketing surveillance data 1
• Low-certainty evidence shows a small increase to no difference in adverse cardiovascular events, with a Peto odds ratio of 1.22 1
• One trial in elderly men with mobility limitations and high prevalence of chronic disease was terminated early due to significantly higher rates of cardiovascular events in the testosterone group (23 subjects) compared to placebo (5 subjects) 2
• However, older studies suggest testosterone may have neutral or possibly beneficial effects on cardiovascular health, with some evidence showing improved coronary blood flow in men with stable angina 3

For elderly patients, particularly those over 70 years with chronic illness or congestive heart failure, use easily titratable formulations (gel, spray, or patch) and target mid-range testosterone levels (350-600 ng/dL) rather than higher physiologic ranges 3, 1

Hematologic Risks

Erythrocytosis represents one of the most common and clinically significant risks:

• The risk of erythrocytosis varies widely by formulation: 3-18% with transdermal administration, up to 44% with injectable testosterone 3, 4
• Elevated hematocrit increases the risk of thromboembolic events, including deep vein thrombosis and pulmonary embolism 1, 5
• Hematocrit must be checked prior to initiating treatment, at 3-6 months after starting, and then annually 5
• Treatment should be withheld if hematocrit exceeds 54%, with consideration of phlebotomy in high-risk cases 1, 4, 5

Injectable testosterone carries higher erythrocytosis risk than transdermal preparations due to supraphysiologic peak levels 4

Prostate-Related Concerns

While the relationship between testosterone and prostate cancer remains controversial:

• Baseline PSA and digital rectal examination should be performed in men over 40 years before initiating therapy 3, 1
• PSA levels often increase with testosterone therapy and require monitoring every 6-12 months 3, 6
• Urologic referral is warranted if PSA increases >1.0 ng/mL during the first 6 months or >0.4 ng/mL per year thereafter 1
• Benign prostatic hyperplasia symptoms may worsen, though this is rarely of clinical significance 3, 5
• Active or treated prostate cancer is an absolute contraindication to testosterone therapy 1, 5

The evidence does not support testosterone causing prostate cancer, but it may accelerate growth of existing disease 3, 7

Other Significant Risks

Fluid Retention and Heart Failure

• Testosterone promotes sodium and water retention, which may precipitate or worsen congestive heart failure in susceptible patients 3, 5
• Use caution in men with preexisting cardiac, renal, or hepatic disease 5

Sleep Apnea

• Testosterone may potentiate sleep apnea, especially in men with obesity or chronic lung disease 3, 5
• This risk is infrequent but clinically important in elderly populations 3

Fertility Suppression

• Exogenous testosterone suppresses spermatogenesis through feedback inhibition of FSH, potentially causing azoospermia 5
• This is particularly relevant for younger men but less concerning in elderly populations 3

Secondary Exposure Risk

• Topical testosterone formulations carry risk of transfer to women and children through skin contact 5
• Application sites must be covered with clothing after gel dries, and sites should be washed thoroughly before anticipated skin-to-skin contact 5

Special Considerations for Elderly Patients

The American Geriatrics Society recommends avoiding testosterone in frail older men with recent cardiovascular events or severe heart failure 1

For elderly men being considered for therapy:

• Confirm biochemical hypogonadism with two morning testosterone measurements below 300 ng/dL 1, 4
• Ensure presence of specific symptoms, particularly diminished libido and erectile dysfunction 1
• Set realistic expectations: testosterone produces small improvements in sexual function (standardized mean difference 0.35) but little to no effect on physical functioning, energy, vitality, or cognition 1, 8
• Consider a 4-6 month trial in men with borderline levels (231-346 ng/dL), continuing only if clinical benefit is demonstrated 3

Monitoring Requirements

Comprehensive monitoring is essential to mitigate risks:

• Testosterone levels at 2-3 months after initiation or dose adjustment, then every 6-12 months 1, 4
• Hematocrit at baseline, 3-6 months, then annually 1, 5
• PSA at baseline and periodically (every 6-12 months) in men over 40 years 3, 1
• Blood pressure and lipid profile periodically 8, 5
• Assessment for signs of fluid retention, sleep apnea, and prostate symptoms 1, 5

Critical Pitfalls to Avoid

• Never initiate testosterone without confirming both low testosterone levels AND specific symptoms 1
• Never use testosterone in men actively seeking fertility—use gonadotropin therapy instead 1, 4
• Never ignore cardiovascular risk factors or recent cardiac events when considering therapy 1, 2
• Never use weekly injectable dosing in elderly patients—this exceeds standard practice and increases erythrocytosis risk 4
• Approximately 20-30% of men receiving testosterone in the United States lack documented low testosterone before treatment, violating evidence-based guidelines 1