Testosterone Replacement Therapy: Patient Information on Risks and Benefits
Key Recommendation
Testosterone replacement therapy (TRT) is indicated for men with confirmed hypogonadism—meaning both documented low testosterone levels (morning total testosterone <300 ng/dL on at least two separate occasions) AND associated symptoms—and can significantly improve sexual function, body composition, bone density, and quality of life, though it carries risks including erythrocytosis, potential cardiovascular effects, and prostate concerns that require ongoing monitoring. 1, 2, 3
Who Should Consider Testosterone Therapy
Diagnostic Requirements
- You need BOTH low testosterone levels AND symptoms to qualify for treatment—not just one or the other 1, 2
- Morning testosterone must be measured between 8-10 AM on two separate occasions, with levels below 300 ng/dL (or free testosterone frankly low by equilibrium dialysis) 4, 2
- Common symptoms include: decreased libido, erectile dysfunction, reduced energy, depressed mood, loss of muscle mass, increased body fat, and reduced bone density 2, 5, 6
Who Should NOT Use Testosterone
- Men with breast or prostate cancer (absolute contraindication) 1, 2, 3
- Men actively trying to conceive (testosterone suppresses sperm production) 2, 5
- Untreated severe sleep apnea or severe heart failure 1
- Men with normal testosterone levels seeking "anti-aging" benefits—this is specifically NOT recommended 1, 2, 5
Expected Benefits of Treatment
Sexual Function (Most Consistent Benefit)
- Significant improvement in libido and sexual function—this is the most reliable benefit you can expect 1, 5
- Positive effects on erectile dysfunction in hypogonadal men 1
Body Composition and Muscle
Bone Health
- Increased bone mineral density, reducing osteoporosis risk, particularly important if you have low bone density 1, 5
Metabolic Benefits
- Improvements in fasting glucose, insulin resistance, and triglyceride levels 4, 2
- Increased HDL cholesterol 4
- May help with weight loss in men with obesity and hypogonadism 4
Other Potential Benefits
- Correction of mild anemia associated with hypogonadism 5
- Possible improvements in mood and depressive symptoms, though evidence is mixed 1, 2
- Overall quality of life improvements 1, 5
Limited or Uncertain Benefits
- Physical functioning, energy/vitality, and cognition show little to no improvement in most studies—don't expect dramatic changes in these areas 1, 2, 5
Risks and Side Effects
Common and Important Risks
Erythrocytosis (Elevated Red Blood Cell Count)
- Occurs in up to 44% of men receiving testosterone injections 1, 5
- Injectable forms carry higher risk than gels or patches 2, 5
- Requires regular blood count monitoring 1, 2
- Treatment may need to be stopped if hematocrit exceeds 54% 2
Prostate-Related Concerns
- Potential worsening of benign prostatic hyperplasia (enlarged prostate) symptoms 5, 3
- Theoretical risk of stimulating occult prostate cancer, though testosterone does not appear to significantly increase prostate cancer risk 1, 5
- Requires regular PSA testing and digital rectal examination, especially if you're over 50 2, 5
Fertility and Testicular Effects
- Testosterone suppresses sperm production and can cause infertility 2, 5
- Testicular atrophy (shrinkage) may occur 2
- If you want to preserve fertility, you need gonadotropin therapy instead—testosterone is absolutely contraindicated 2
Cardiovascular Considerations
- Current evidence suggests neutral or possibly beneficial cardiovascular effects, but long-term safety data remains limited 1, 5
- The FDA has required ongoing studies to evaluate long-term cardiovascular outcomes 5
Other Side Effects
- Fluid retention (rarely clinically significant) 5, 3
- Acne or oily skin 2, 5
- Gynecomastia (breast enlargement) may develop and occasionally persists 3
- Sleep apnea may worsen in predisposed individuals 5
Serious but Rare Risks (with high-dose or prolonged use)
- Liver toxicity, hepatic adenomas, and hepatocellular carcinoma (primarily with oral 17-α alkyl-androgens, not typical TRT formulations) 3
- Hypercalcemia in immobilized patients 3
Treatment Options and What to Expect
Available Formulations
Transdermal Gels/Patches (Often Preferred Initially)
- Applied daily to skin 4, 2
- Provides stable day-to-day testosterone levels 4, 2
- More expensive (approximately $2,135 annually) 2
- Preferred for convenience and avoiding injections 4, 2
Intramuscular Injections (Testosterone Cypionate/Enanthate)
- Administered every 2-3 weeks 2, 5
- More economical (approximately $156 annually) 2
- Peak levels occur 2-5 days after injection, with return to baseline 10-14 days later 2, 5
- Higher risk of erythrocytosis compared to transdermal forms 2, 5
Oral Testosterone Undecanoate
- Taken twice daily 8
- Demonstrated 87% of patients achieving testosterone levels within normal range 8
- Comparable safety to other formulations 8
Monitoring Requirements
Initial Phase (First 2-3 Months)
- Testosterone levels checked 2-3 months after starting or after dose changes 2
- Target mid-normal range (500-600 ng/dL for injections, 350-750 ng/dL overall) 1, 2
- Hematocrit monitoring to detect erythrocytosis 1, 2
- PSA and digital rectal examination if over 40-50 years old 2, 5
Long-Term Monitoring (Every 6-12 Months)
- Testosterone levels once stable on a given dose 2
- Annual hematocrit 5
- Annual prostate cancer screening (PSA and digital rectal exam) for men over 50 5, 9
Important Considerations
Treatment Duration and Expectations
- If you see no improvement in sexual function after 12 months, treatment should be discontinued 2, 5
- Long-term efficacy and safety data are limited, particularly for younger men (18-50 years) 2
- Benefits for symptoms other than sexual function may be modest 5
Special Populations
Men with Obesity
- Weight loss through diet can improve testosterone levels in obesity-associated hypogonadism 2
- Free testosterone measurement by equilibrium dialysis is essential, as total testosterone may be misleadingly low due to low sex hormone-binding globulin 4
- Treatment should only be considered when free testosterone is frankly low on at least two separate assessments 4
Elderly Men
- TRT should primarily be used to improve sexual function, not for energy, vitality, physical function, or cognition 2
- Small improvements in quality of life and sexual function are expected, but effects on other symptoms are minimal 2, 5
Cost Considerations
- Patient preference matters: some prefer gels for convenience despite higher cost, others choose injections for affordability 2
- Injectable testosterone is significantly more economical if cost is a concern 2
Common Pitfalls to Avoid
- Do not use testosterone for "low energy" or "anti-aging" without documented low testosterone and symptoms—this is specifically not recommended 1, 2, 5
- Do not start testosterone if you're trying to conceive—it will suppress fertility 2, 5
- Do not skip monitoring—erythrocytosis and prostate changes require regular surveillance 1, 2, 5
- Do not expect dramatic improvements in energy, physical function, or cognition—evidence for these benefits is weak 1, 2, 5