The Complete Guide to Testosterone Replacement Therapy
Hormones15 minMarch 1, 2026

The Complete Guide to Testosterone Replacement Therapy

Understanding TRT protocols, monitoring, and optimization strategies

Understanding Low Testosterone

Testosterone deficiency (hypogonadism) affects an estimated 20-40% of men over age 45. Symptoms are often gradual and attributed to "normal aging," but they significantly impact quality of life:

  • Fatigue and low energy
  • Decreased libido and erectile dysfunction
  • Loss of muscle mass and increased body fat
  • Depression, irritability, and brain fog
  • Poor sleep quality
  • Decreased bone density

Diagnosis

Proper diagnosis requires both symptoms AND confirmed low testosterone levels on blood testing. Key labs include:

Essential: Total Testosterone, Free Testosterone, SHBG, Estradiol (sensitive), LH, FSH, CBC (hematocrit), Comprehensive Metabolic Panel

Additional: Prolactin, Thyroid panel (TSH, Free T3, Free T4), PSA, Lipid panel, DHEA-S, IGF-1

Testing should be done fasting, in the morning (before 10 AM), as testosterone levels follow a circadian rhythm with peak levels in the early morning.

TRT Protocol Options

Testosterone Cypionate/Enanthate Injections

The most common and cost-effective approach. Typical starting dose is 100-120 mg/week, split into 2 injections (e.g., 50-60 mg every 3.5 days) for more stable blood levels.

Advantages: Precise dosing, cost-effective, well-studied Considerations: Requires injections, some men dislike needles

Testosterone Cream/Gel

Applied daily to the skin (typically shoulders, inner thighs, or scrotum). Scrotal application produces higher DHT levels.

Advantages: No injections, daily application mimics natural rhythm Considerations: Transfer risk to partners/children, variable absorption, more expensive

Testosterone Pellets

Implanted subcutaneously every 3-6 months. Provides steady-state levels.

Advantages: Convenience, steady levels Considerations: Minor surgical procedure, difficult to adjust dose, potential extrusion

Ancillary Medications

HCG (Human Chorionic Gonadotropin)

Maintains testicular size, fertility, and intratesticular hormone production. Typical dose: 250-500 IU, 2-3 times per week.

Anastrozole

Aromatase inhibitor used to manage estradiol levels if they rise too high. Used judiciously — the goal is optimal estradiol, not suppressed estradiol. Typical dose: 0.25-0.5 mg, 1-3 times per week as needed.

Enclomiphene

Can be used as a TRT alternative (stimulates endogenous production) or alongside TRT to maintain some HPG axis function.

Monitoring

Regular bloodwork is essential. Check labs at 6-8 weeks after starting or adjusting dose, then every 3-6 months once stable:

  • Total and Free Testosterone (target: 700-1100 ng/dL total)
  • Estradiol sensitive (target: 20-35 pg/mL)
  • Hematocrit (watch for >54%)
  • PSA (prostate screening)
  • Lipid panel
  • Comprehensive metabolic panel

Common Mistakes

  1. Starting dose too high — Start conservative and titrate up based on labs and symptoms
  2. Infrequent injections — Once-weekly or biweekly injections cause hormone rollercoasters; split into 2+ doses per week
  3. Over-using aromatase inhibitors — Crashed estradiol feels worse than high estradiol
  4. Ignoring hematocrit — Donate blood if hematocrit rises above 52-54%
  5. Not addressing root causes — Sleep, stress, diet, and exercise all affect testosterone; TRT works best as part of a comprehensive approach

Lifestyle Optimization

TRT works synergistically with lifestyle factors:

  • Sleep: 7-9 hours of quality sleep
  • Exercise: Resistance training 3-4x/week, moderate cardio
  • Nutrition: Adequate protein, healthy fats, micronutrient sufficiency
  • Stress management: Chronic stress elevates cortisol, which antagonizes testosterone
  • Body composition: Excess body fat increases aromatization