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Also known as
TRT, Androgen Replacement Therapy, Testosterone Therapy, Hormone Replacement Therapy for Men, T Therapy, Androgen Supplementation
Definition
Testosterone replacement therapy (TRT) is a medical intervention designed to restore and maintain physiological testosterone levels in individuals with hypogonadism, a clinical syndrome characterized by persistently low serum testosterone levels accompanied by symptoms of testosterone deficiency.1 This therapy involves the administration of exogenous testosterone through various formulations to compensate for inadequate endogenous production.2 TRT aims to alleviate symptoms associated with testosterone deficiency, including decreased libido, erectile dysfunction, fatigue, depressed mood, and reduced muscle mass, while inducing and maintaining secondary sex characteristics.3 The therapy does not address the underlying cause of hypogonadism but rather supplements the deficient hormone to achieve normal physiological levels, typically targeting a range of 300-1000 ng/dL depending on laboratory standards and individual patient factors.4
Clinical Context
Testosterone replacement therapy is primarily indicated for men with confirmed hypogonadism, which occurs in approximately 19% of men in their 60s, 28% in their 70s, and 49% in their 80s.1 Diagnosis requires at least two documented low morning serum testosterone measurements (typically below 300 ng/dL) in conjunction with symptoms consistent with testosterone deficiency.2
Before initiating therapy, clinicians must distinguish between primary (testicular) and secondary (pituitary-hypothalamic) hypogonadism through comprehensive evaluation including medical history, physical examination, and laboratory testing.3 Initial laboratory assessment should include two early morning testosterone measurements, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid-stimulating hormone (TSH), complete blood count (CBC), prostate-specific antigen (PSA) for men over 40, and a comprehensive metabolic panel.2
Multiple administration methods are available, each with distinct advantages and considerations:4
- Transdermal gels (applied to shoulders, upper arms, or abdomen)
- Intramuscular injections (testosterone enanthate or cypionate)
- Subcutaneous injections
- Testosterone patches
- Testosterone pellets (implanted subdermally)
- Buccal testosterone tablets
- Testosterone nasal gel
- Oral testosterone formulations
Treatment selection should consider patient preference, pharmacokinetics, potential medication interactions, formulation-specific adverse effects, treatment burden, and cost.1 Clinicians should monitor patients receiving TRT for symptom improvement, potential adverse effects, and adherence.3 Regular monitoring includes assessment of serum testosterone, hematocrit, and PSA levels at baseline and at least annually in men 40 years or older.1
Evidence suggests that TRT may improve sexual function, depressive symptoms, bone density, and lean body mass.1 While earlier studies raised concerns about cardiovascular risks, recent large randomized trials indicate that TRT does not increase the risk of myocardial infarction or stroke, even in high-risk patients.1 However, TRT is contraindicated in men seeking fertility preservation, as it significantly decreases sperm production.2 Alternative approaches such as clomiphene citrate or human chorionic gonadotropin may be considered for hypogonadal men wishing to maintain fertility.2