What is Testosterone Replacement Therapy?

Overview of low testosterone, how it’s diagnosed, and treatment options with testosterone replacement therapy.

Men's Health

Testosterone Replacement Therapy

2025-09-11

Intro

Testosterone is the primary male sex hormone, vital for sexual function, energy, muscle mass, and mood. Low testosterone (hypogonadism) can affect quality of life and long-term health. Testosterone replacement therapy (TRT) may restore levels, but it requires careful diagnosis and monitoring.

Key Points

Symptoms of low testosterone include fatigue, reduced libido, mood changes, and muscle loss.
Diagnosis requires both symptoms and laboratory confirmation of low serum testosterone.
Testing is done in the morning, often on at least two occasions, with total testosterone <300 ng/dL (~10.4 nmol/L) as a common cutoff.
Treatment options include injections, gels, patches, pellets, and oral formulations.
Risks/benefits: TRT can improve energy, libido, and bone/muscle health, but carries risks such as fertility suppression, prostate monitoring concerns, and possible cardiovascular effects.

Background

Testosterone levels decline naturally with age, but true hypogonadism results from testicular, pituitary, or hypothalamic dysfunction. It is important to distinguish normal aging from clinically significant deficiency.

Causes or Mechanisms

Primary hypogonadism: testicular failure (e.g., Klinefelter syndrome, injury, chemotherapy).
Secondary hypogonadism: pituitary or hypothalamic dysfunction (e.g., tumors, chronic illness, obesity).
Age-related decline: gradual decrease, but not always requiring TRT.

Diagnosis and Laboratory Findings

When to test: men with consistent symptoms (fatigue, low libido, erectile dysfunction, depression, decreased muscle/bone mass).
Blood test: total testosterone, drawn in the morning (7–10 am).
Confirming low T: typically <300 ng/dL (10.4 nmol/L). Reference ranges vary by lab.
Additional tests: free testosterone, LH, FSH, prolactin, SHBG to determine cause.
Repeat testing: needed to confirm abnormal results.

Types of Testosterone Replacement Therapy

Intramuscular injections (testosterone enanthate, cypionate, undecanoate): given every 1–12 weeks depending on preparation.
Transdermal gels/creams: applied daily, steady absorption, risk of skin transfer.
Patches: applied daily, can cause skin irritation.
Subcutaneous pellets: implanted under skin, last 3–6 months.
Oral testosterone undecanoate: absorbed via lymphatic system, newer option in some regions.

Risks / Benefits / Prognosis

Benefits: improved libido, energy, muscle strength, bone density, mood.
Risks: acne, fluid retention, breast enlargement, reduced fertility (sperm suppression), polycythemia (high red cell count).
Long-term concerns: cardiovascular risk is debated; prostate cancer screening required before and during TRT.
Prognosis: most men respond well if carefully selected, monitored, and managed.

FAQ

Q: Who should consider TRT?
A: Men with both symptoms of low testosterone and consistently low lab results.

Q: Can TRT restore fertility?
A: No. In fact, TRT usually suppresses sperm production. Other treatments (e.g., clomiphene, gonadotropins) may be used if fertility is desired.

Q: How often are labs monitored?
A: Typically at 3–6 months after starting therapy, then annually (testosterone, hematocrit, PSA, liver function, lipid profile).

Q: Is TRT safe long-term?
A: Evidence is mixed; it can be safe with monitoring, but risks include blood thickening, prostate enlargement, and uncertain cardiovascular effects.