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Testosterone (TRT)

Testosterone Replacement Therapy

Hormone Replacement Therapy

Last updated: December 2024

Evidence Level: Strong Evidence

Multiple large human trials, FDA approval, established safety profile

Regulatory Status: FDA-approved for treatment of hypogonadism (low testosterone)

Testosterone replacement therapy (TRT) is the medical treatment for men with clinically low testosterone (hypogonadism). It involves supplementing testosterone through injections, gels, patches, or pellets to bring levels back to a healthy range. When properly prescribed and monitored, TRT can significantly improve energy, mood, libido, body composition, and overall quality of life. It's one of the most impactful hormone interventions available—but it's not without trade-offs.

How It Works

Testosterone is the primary male sex hormone, produced mainly in the testes. It affects nearly every system in a man's body:

What testosterone does:
• Maintains muscle mass and bone density
• Regulates fat distribution and metabolism
• Drives libido and sexual function
• Affects mood, energy, and cognitive function
• Supports red blood cell production

Why levels decline:
Testosterone naturally decreases about 1% per year after age 30. But many men experience faster declines due to obesity, stress, poor sleep, or underlying medical conditions. Some men have primary hypogonadism (the testes don't produce enough) or secondary hypogonadism (the brain doesn't signal the testes properly).

How TRT works:
External testosterone replaces what your body isn't making. This raises blood testosterone levels, restoring the hormone's effects throughout your body. The trade-off: when you add external testosterone, your body's natural production shuts down. The testes receive less signaling and produce less testosterone and sperm.

Potential Benefits

  • Improved energy and reduced fatigue
  • Increased muscle mass and reduced body fat (with exercise)
  • Enhanced libido and sexual function
  • Better mood and reduced depression symptoms
  • Improved cognitive function and mental clarity
  • Increased bone density (long-term)
  • Better motivation and sense of well-being

Risks & Considerations

  • Suppresses natural testosterone production (usually permanent with long-term use)
  • Reduces sperm production (can cause infertility—often reversible with HCG or stopping TRT)
  • May increase hematocrit/red blood cells (requires monitoring; can increase clot risk)
  • Possible acne and oily skin
  • Potential for estrogen conversion (may need estrogen management)
  • Testicular atrophy (shrinkage) due to reduced natural production
  • Requires lifelong commitment for most users
  • Mood changes possible during dose adjustments
  • Cardiovascular risk debate (recent studies suggest it's safer than once thought)

Dosing Information

TRT protocols vary significantly between clinics and individual needs. The goal is achieving testosterone levels in the upper-normal range while minimizing side effects.

  • Typical injection dose: 100-200mg testosterone cypionate/enanthate weekly
  • Some protocols use twice-weekly injections for more stable levels
  • Gels: Daily application (AndroGel, Testim)—convenient but expensive and transfer risk
  • Patches: Daily (Androderm)—less common due to skin irritation
  • Pellets: Implanted every 3-6 months (Testopel)—convenient but less adjustable
  • Target: Most aim for Total T of 600-900 ng/dL (varies by individual)
  • Free testosterone and SHBG matter as much as total testosterone

Practical Tips

  • 1Get comprehensive baseline testing before starting (Total T, Free T, SHBG, estradiol, CBC, PSA)
  • 2Test testosterone in the morning when levels are highest
  • 3Self-injection is common and not as intimidating as it sounds (subcutaneous works well)
  • 4Monitor hematocrit every 3-6 months (donate blood if it gets too high)
  • 5Consider HCG if fertility preservation is important (maintains testicular function)
  • 6Dial in your protocol over months—expect adjustments
  • 7Some men need estrogen management (anastrozole) if they aromatize heavily
  • 8Lifestyle still matters: TRT amplifies results from exercise and good nutrition

Key Research

TRAVERSE Trial

New England Journal of Medicine, 2023

TRT did not increase cardiovascular events vs placebo in men with hypogonadism and pre-existing cardiovascular risk. Major safety concern addressed.

Testosterone Trials (TTrials)

JAMA / New England Journal of Medicine, 2016

TRT improved sexual function, physical function, and mood in men over 65 with low testosterone. Benefits were moderate but consistent.

Meta-analysis on bone density

Journal of Clinical Endocrinology & Metabolism

TRT increases bone mineral density in hypogonadal men, reducing fracture risk over the long term.

Disclaimer: This information is for educational purposes only and is not medical advice. Always consult with a qualified healthcare provider before starting any treatment. Evidence levels and regulatory status can change—this content was last updated December 2024.