Can testosterone therapy cause benign prostatic hyperplasia (BPH)?

Testosterone's Effect on Prostate Enlargement

Testosterone therapy can cause an increase in prostate volume but typically does not worsen urinary symptoms in most men with benign prostatic hyperplasia (BPH). 1 While testosterone is required for the development of BPH, testosterone replacement therapy (TRT) generally does not exacerbate lower urinary tract symptoms.

Relationship Between Testosterone and BPH

BPH is a histologic diagnosis that refers to the proliferation of prostatic tissue, which requires testosterone for development. 2 The pathophysiology involves:

• Testosterone is converted to dihydrotestosterone (DHT) by 5α-reductase enzymes
• DHT has a higher affinity for androgen receptors and is considered the more potent androgenic hormone
• The DHT-androgen receptor complex initiates cellular growth in the prostate

Despite this relationship, the evidence shows that:

• Prostate volume increases significantly during testosterone therapy, mainly during the first six months of treatment 2
• This increase brings the prostate size to levels equivalent to men without hypogonadism 1
• Despite increased volume, urine flow rates, post-void residual volumes, and voiding symptoms typically do not worsen significantly 2

Clinical Evidence

Multiple studies have demonstrated that:

• Testosterone replacement therapy does not typically exacerbate voiding symptoms attributable to BPH 2
• Complications such as urinary retention have not occurred at higher rates in men on TRT compared to those receiving placebo 2
• The apparent paradox between increased prostate volume and stable urinary symptoms is explained by the poor correlation between prostate volume and urinary symptoms 2

Monitoring Recommendations

For patients receiving testosterone therapy who may have or develop BPH:

• Monitor patients with BPH for worsening signs and symptoms 3
• Measure baseline PSA and perform digital rectal examination before initiating therapy 1
• Assess baseline urinary symptoms using standardized tools like IPSS 1
• Check hematocrit prior to initiating treatment and periodically thereafter 3
• Continue PSA monitoring according to standard guidelines for men without testosterone deficiency 1

Important Clinical Considerations

• Individual responses vary, and some men may experience increased voiding symptoms with testosterone therapy 2
• For patients with larger prostates who develop worsening symptoms on TRT, consider:
  • Dose reduction of testosterone
  • Addition of alpha-blockers
  • Possible addition of 5-alpha reductase inhibitors for long-term management 1

Mechanism Explanation

The development of BPH is likely multifactorial, with testosterone playing a permissive rather than causative role. 4 Several factors explain why TRT doesn't necessarily worsen BPH symptoms:

• BPH development involves an imbalance between growth and apoptosis in favor of growth 2
• Growth factors (TGF-β, FGF, IGF) are key regulators of cell proliferation 4
• Estrogens and their receptors, which increase with age, may play a significant role in BPH development 5
• The "saturation model" suggests that maximal androgen-stimulated prostate growth is achieved at relatively low testosterone concentrations 6

In conclusion, while testosterone is necessary for BPH development and TRT can increase prostate volume, it typically does not significantly worsen urinary symptoms in most men. Proper monitoring and management can mitigate potential risks in those who do experience symptom exacerbation.