# TRT Safety & Risks

> Medically reviewed by Dr. Michael Chen, MD — Board-certified Endocrinologist
> Last updated: February 2026

## Short-Term Side Effects

Most short-term side effects are manageable and often resolve with dose adjustment:

| Side Effect | Frequency | Management |
|---|---|---|
| Acne or oily skin | Common | Skincare adjustments, dose reduction if severe |
| Injection site reactions | Common (injections) | Rotate injection sites, proper technique |
| Fluid retention | Common initially | Usually resolves; may require dose adjustment |
| Mood fluctuations | Uncommon | Often related to dose timing or estrogen levels |
| Testicular atrophy | Common | Expected due to HPG axis suppression; hCG can mitigate |
| Increased body hair | Common | Cosmetic only; no medical concern |
| Breast tenderness (gynecomastia) | Uncommon | May indicate elevated estrogen; managed with aromatase inhibitors |

## Long-Term Risks

### Polycythemia (Elevated Red Blood Cells)
- **What it is:** TRT stimulates erythropoiesis (red blood cell production), which can raise hematocrit levels
- **Risk:** Elevated hematocrit (above 54%) increases blood viscosity and clot risk
- **Monitoring:** CBC checked at every follow-up
- **Management:** Dose reduction, therapeutic phlebotomy (blood donation), or treatment discontinuation if severe

### Fertility Suppression
- **What it is:** TRT suppresses LH and FSH, leading to reduced or absent sperm production
- **Risk:** Infertility during treatment; recovery is possible but not guaranteed after discontinuation
- **Management:** hCG co-administration to maintain testicular function; clomiphene as an alternative to TRT for men prioritizing fertility
- **Recovery timeline:** 6-12+ months after stopping TRT; some men may not fully recover

### Sleep Apnea
- **What it is:** TRT may worsen existing obstructive sleep apnea
- **Risk:** Increased sleep disruption, cardiovascular strain
- **Management:** Screen for sleep apnea before starting TRT; treat with CPAP if present

## Cardiovascular Considerations

The relationship between TRT and cardiovascular health has been extensively studied with mixed results:

### What the Evidence Shows
- **TRAVERSE trial (2023):** The largest randomized controlled trial of TRT found no increased risk of major adverse cardiovascular events (MACE) in men with hypogonadism and cardiovascular risk factors
- **Some observational studies** have suggested potential cardiovascular risk, particularly in older men with pre-existing conditions
- **Other studies** suggest TRT may improve cardiovascular risk markers, including insulin sensitivity, body composition, and lipid profiles

### Current Clinical Consensus
- TRT does not appear to significantly increase cardiovascular risk in appropriately selected patients
- Men with pre-existing cardiovascular disease should be monitored more closely
- Cardiovascular risk factors (obesity, diabetes, hypertension, smoking) should be addressed alongside TRT
- Regular lipid panel monitoring is standard practice during TRT

## Prostate Screening

### TRT and Prostate Health
- **Historical concern:** TRT was once thought to cause prostate cancer, but modern evidence does not support this
- **Current understanding:** TRT does not increase the incidence of prostate cancer in men without pre-existing disease
- **PSA monitoring:** PSA should be checked at baseline and periodically during treatment
- **Red flags:** A significant PSA rise (>1.4 ng/mL within 12 months) or abnormal digital rectal exam warrants urological evaluation
- **Contraindication:** Active or untreated prostate cancer remains an absolute contraindication to TRT

## Monitoring and Lab Frequency

### Minimum Monitoring Protocol

| Test | Baseline | 6-8 Weeks | 3 Months | 6 Months | Annual |
|---|---|---|---|---|---|
| Total Testosterone | ✅ | ✅ | ✅ | ✅ | ✅ |
| Free Testosterone | ✅ | | ✅ | | ✅ |
| Hematocrit/CBC | ✅ | ✅ | ✅ | ✅ | ✅ |
| Estradiol (E2) | ✅ | ✅ | ✅ | | ✅ |
| PSA | ✅ | | | ✅ | ✅ |
| Lipid Panel | ✅ | | | ✅ | ✅ |
| Metabolic Panel | ✅ | | | | ✅ |
| Liver Function | ✅ | | | | ✅ |

### Warning Signs to Report Immediately
- Chest pain or shortness of breath
- Severe headaches or vision changes
- Leg swelling or pain (possible blood clot)
- Difficulty urinating or blood in urine
- Severe mood changes or depression
- Excessive bruising or bleeding

## Risk Mitigation Strategies

1. **Start at the lowest effective dose** — begin conservatively and titrate up
2. **Regular blood work** — never skip scheduled monitoring
3. **Report symptoms promptly** — early intervention prevents complications
4. **Maintain cardiovascular health** — exercise, healthy diet, and weight management
5. **Limit alcohol** — excessive alcohol affects hormone metabolism
6. **Choose a qualified provider** — licensed physicians with hormone therapy experience
7. **Don't share medications** — testosterone is a controlled substance prescribed for individual use

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*This content is for informational purposes only and does not constitute medical advice. Always consult with a licensed healthcare provider before starting any hormone therapy.*