Does testosterone therapy cause prostate enlargement in older men?

Testosterone Therapy and Prostate Enlargement in Older Men

Testosterone therapy does cause prostate enlargement in older men, but this increase in prostate volume typically does not worsen urinary symptoms or lead to significant clinical consequences. 1

Mechanism and Effects on Prostate Volume

• Testosterone therapy increases prostate volume, primarily during the first six months of treatment, bringing the prostate size to levels equivalent to men without hypogonadism 1
• The pathophysiology involves the conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase enzymes, with DHT having higher affinity for androgen receptors 1
• The FDA label for testosterone products acknowledges that "geriatric patients treated with androgens may be at an increased risk of developing prostatic hypertrophy," though notes that "conclusive evidence to support this concept is lacking" 2

Clinical Impact on Urinary Symptoms

• Despite increased prostate volume, urine flow rates, post-void residual volumes, and voiding symptoms typically do not worsen significantly 1
• The American Urological Association indicates that testosterone replacement therapy does not typically exacerbate voiding symptoms attributable to BPH 1
• This apparent paradox between increased prostate volume and stable urinary symptoms is explained by the poor correlation between prostate size and urinary symptoms 1

Evidence from Recent Clinical Trials

• In a 2023 randomized clinical trial involving 5,204 men (mean age 63.3 years) followed for a mean of 21.8 months, testosterone therapy did not significantly increase the incidence of acute urinary retention, invasive prostate procedures, or new pharmacologic treatment for lower urinary tract symptoms compared to placebo 3
• Changes in International Prostate Symptom Score (IPSS) did not differ between testosterone-treated and placebo-treated groups, despite increases in PSA levels in the testosterone group 3

Saturation Model Explanation

• The "Saturation Model" helps explain why testosterone therapy doesn't dramatically worsen prostate conditions 4
• This model posits a finite capacity of androgens to stimulate prostate growth, meaning that once androgen receptors are fully saturated (which occurs at relatively low testosterone levels), additional testosterone does not cause further growth 4

Monitoring Recommendations

• Before starting testosterone therapy:

  • Measure baseline PSA in men over 40 years
  • Perform digital rectal examination
  • Assess baseline urinary symptoms using IPSS
  • Check hematocrit levels 1

• During treatment:

  • Monitor for changes in urinary symptoms, especially in the first 6 months
  • Be aware that prostate volume typically increases during this period
  • Consider dose reduction of testosterone or addition of alpha-blockers if significant worsening of urinary symptoms occurs 1
  • Continue PSA monitoring following standard guidelines for men without testosterone deficiency 1

Clinical Implications

• For patients with larger prostates or existing urinary symptoms, consider combination therapy with a 5-alpha reductase inhibitor for long-term management 1
• Individual responses to testosterone therapy vary, so close monitoring is essential, especially during the first 6 months 1
• Contrary to historical concerns, modern studies indicate no increased risk of prostate cancer among men with serum testosterone in the therapeutic range 4

While testosterone therapy does cause prostate enlargement in older men, the clinical significance of this enlargement is typically minimal, with no significant worsening of urinary symptoms in most patients. Proper monitoring and management strategies can further mitigate any potential risks.