Testosterone Replacement Therapy: Benefits and Risks
Testosterone replacement therapy (TRT) is generally safe for men with confirmed hypogonadism when properly monitored, with benefits that typically outweigh the risks for appropriate candidates. 1
Benefits of TRT
- TRT improves multiple aspects of quality of life in hypogonadal men, including libido, sexual function, bone density, muscle mass, body composition, mood, and energy levels 1, 2
- TRT can increase muscle mass and reduce body fat, leading to improved body composition in men with hypogonadism 1
- TRT improves bone mineral density, reducing the risk of osteoporosis in men with low bone density 1
- TRT may improve metabolic parameters, including insulin sensitivity, particularly in men with metabolic syndrome 1
- TRT can reduce depressive symptoms and may have cognitive benefits in hypogonadal men 1
Cardiovascular Considerations
- Current evidence suggests TRT has either a neutral or possibly beneficial effect on cardiovascular health, contrary to some historical concerns 2, 1
- The FDA has noted that epidemiologic studies and randomized controlled trials have been inconclusive regarding the risk of major adverse cardiovascular events (MACE) with testosterone use 3
- Recent high-quality studies have not found significant differences in cardiovascular adverse events between TRT and placebo groups 2
- Fluid retention can occur with TRT and requires caution in patients with pre-existing cardiac, renal, or hepatic disease 3
Prostate Considerations
- TRT does not appear to significantly increase prostate cancer risk, though monitoring is still recommended 2
- Prostate volume typically increases during the first six months of TRT to levels equivalent to men without hypogonadism, but this rarely causes significant urinary symptoms 2
- Regular monitoring of PSA is recommended during TRT 2:
- Perform prostate biopsy for PSA increase of 1.0 ng/ml in any year
- If PSA rises by 0.7–0.9 ng/ml, repeat PSA measurement in 3–6 months and perform biopsy for any further increase
Other Potential Risks and Side Effects
- Erythrocytosis (elevated red blood cell count) is common, occurring in 3-18% with transdermal administration and up to 44% with injections 2
- Sleep apnea may be exacerbated by TRT, particularly in men with other risk factors for sleep-disordered breathing 2
- Testicular atrophy and reduced fertility are common side effects, especially in younger men, though usually reversible after cessation of treatment 2
- Skin reactions occur in up to 66% of patch users and 5% of gel users 2
- Gynecomastia (breast enlargement) may develop and occasionally persist 3
Contraindications
- Absolute contraindications include breast cancer, untreated prostate cancer, and desire for fertility in the near future 2
- Relative contraindications include severe untreated sleep apnea and uncontrolled/severe heart failure 2
- Oral testosterone preparations available in the US should be avoided due to potential hepatotoxicity 2
Monitoring Recommendations
Before starting TRT:
- Measure baseline testosterone levels (two morning samples)
- Perform prostate examination and PSA testing
- Check hematocrit levels
- Consider prostate biopsy in high-risk patients 2
During TRT:
Treatment Approach
Select an appropriate TRT formulation based on patient preference, cost, and clinical factors 1:
- Transdermal gels/patches: More consistent levels but skin reactions possible
- Intramuscular injections: Cost-effective but may cause fluctuating levels
- Newer formulations: Nasal and buccal options available with different pharmacokinetic profiles
Start with recommended dose and titrate based on serum testosterone levels and symptom response 1
TRT remains a valuable treatment option for men with confirmed hypogonadism, with evidence suggesting the benefits outweigh the risks when properly prescribed and monitored. However, it should not be used for age-related decline in testosterone without clear symptoms and documented low testosterone levels 1.