What are the recommendations for managing declining testosterone levels in individuals over time?

Managing Declining Testosterone Levels in Men Over Time

Lifestyle modifications should be the first-line approach for managing age-related testosterone decline, as they can increase total testosterone levels and reduce symptoms while avoiding potential risks of testosterone therapy. 1

Understanding Testosterone Decline

Testosterone levels naturally decline in men starting in their mid-30s at an average rate of 1.6% per year 1. This age-related decline affects approximately:

• 20% of men older than 60
• 30% of men older than 70
• 50% of men older than 80 1

Several epidemiological studies have associated low testosterone levels with increased all-cause and cardiovascular mortality 1, though causality remains uncertain.

Diagnostic Approach

When evaluating a man with suspected testosterone deficiency:

1. Measure morning total testosterone levels using an accurate and reliable assay 2
2. Confirm low levels by repeating the measurement on a different day 2
3. Measure luteinizing hormone (LH) to distinguish between primary testicular failure and hypothalamic-pituitary disorders 2
4. Measure prolactin when LH is low or low/normal with low testosterone 2
5. Consider pituitary MRI if testosterone levels are severely low (<150 ng/dL) 2

Treatment Recommendations

First-Line: Lifestyle Modifications

• Weight loss/maintenance within recommended range
• Increased physical activity
• Smoking cessation
• Healthy diet (e.g., Mediterranean diet)
• Moderate alcohol consumption 1

These modifications can increase total testosterone levels and reduce symptoms associated with testosterone deficiency 1.

Second-Line: Testosterone Therapy

Testosterone therapy should be considered only for men with:

1. Symptoms consistent with testosterone deficiency
2. Unequivocally and consistently low serum testosterone concentrations 3

Indications:

• Sexual dysfunction that has not improved with lifestyle modifications 1

Contraindications:

• Planning fertility in the near term
• Breast or prostate cancer
• Palpable prostate nodule
• PSA > 4 ng/mL (or > 3 ng/mL in high-risk men)
• Elevated hematocrit
• Untreated severe obstructive sleep apnea
• Severe lower urinary tract symptoms
• Uncontrolled heart failure
• Recent myocardial infarction or stroke (within 6 months)
• Thrombophilia 3

Important Considerations:

1. Cardiovascular risk: Counsel patients that it cannot be stated definitively whether testosterone therapy increases or decreases cardiovascular events 1
2. Wait period: Do not commence testosterone therapy for 3-6 months after cardiovascular events 1
3. Target levels: Aim for total testosterone levels in the mid-normal range (450-600 ng/dL) 1
4. Formulation choice: Consider intramuscular rather than transdermal formulations due to lower cost with similar effectiveness 1
5. Avoid alkylated oral testosterone due to safety concerns 1
6. Fertility impact: Exogenous testosterone therapy should not be prescribed to men currently trying to conceive 1

Monitoring:

• Reassess symptoms within 12 months and periodically thereafter
• Discontinue treatment if no improvement in sexual function occurs 1
• Monitor testosterone levels, hematocrit, and prostate cancer risk 3

Evidence Quality and Limitations

The evidence for testosterone therapy has significant limitations:

• No large-scale, long-term studies have assessed benefits and risks 1
• Most studies show low-certainty evidence for benefits 1
• Concerns about potential risks have limited comprehensive research 1

Despite these limitations, testosterone prescriptions have increased substantially, with a 500% increase in prescription sales since 1993 1.

Common Pitfalls to Avoid

1. Overdiagnosis: Not confirming low testosterone with repeated morning measurements
2. Inadequate workup: Failing to measure LH to determine the cause of hypogonadism
3. Inappropriate treatment: Prescribing testosterone for non-specific symptoms without confirmed low levels
4. Missing serious conditions: Failing to consider pituitary pathology in men with severely low testosterone
5. Fertility concerns: Not discussing potential impact on fertility before starting treatment

By following these evidence-based recommendations, clinicians can appropriately manage age-related testosterone decline while minimizing risks and optimizing outcomes.