Requirements for Testosterone Replacement Therapy (TRT)
Diagnostic Requirements
TRT requires BOTH confirmed biochemical hypogonadism AND specific symptoms—neither alone is sufficient for treatment. 1, 2
Biochemical Confirmation (Mandatory)
- Measure morning total testosterone (8-10 AM) on TWO separate occasions, with both values <300 ng/dL (some guidelines use 275-350 ng/dL threshold) 1, 3
- If total testosterone is borderline (near 300 ng/dL), measure free testosterone by equilibrium dialysis or calculate free androgen index, especially in men with obesity, diabetes, or conditions affecting SHBG 1, 3
- Measure LH and FSH after confirming low testosterone to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism—this distinction is critical for treatment selection 1, 4
Required Symptoms (Mandatory)
The primary symptoms that justify TRT are:
- Diminished libido 1, 3
- Erectile dysfunction 1, 3
- Diminished sense of vitality (weaker evidence for improvement) 1
Symptoms that do NOT justify TRT alone (minimal to no proven benefit):
- Fatigue or low energy (standardized mean difference only 0.17) 1
- Depressed mood (standardized mean difference only -0.19) 1
- Reduced physical function or muscle weakness 1
- Cognitive complaints 1
Absolute Contraindications to TRT
Do not initiate TRT if ANY of the following are present:
- Active desire for fertility preservation—TRT causes azoospermia; use gonadotropin therapy (hCG + FSH) instead 1, 4, 3
- Active or treated male breast cancer 1, 3
- Prostate cancer (though evidence is evolving, this remains a contraindication) 1, 3
- Hematocrit >54% 1, 3
- Untreated severe obstructive sleep apnea 3
- Myocardial infarction or stroke within the past 6 months 1
- Uncontrolled severe heart failure 3
- PSA >4.0 ng/mL (or >3.0 ng/mL in high-risk men) without urologic evaluation 3
- Palpable prostate nodule or induration without negative biopsy 3
Pre-Treatment Workup Required
Before initiating TRT, complete the following:
- Baseline hematocrit/hemoglobin to monitor for erythrocytosis risk 1
- PSA level and digital rectal examination in men >40 years 5, 1, 3
- Prolactin level if testosterone is low or loss of libido is present 5, 1
- Fasting glucose to exclude diabetes 5
- Iron saturation if secondary hypogonadism is suspected 1
- Consider pituitary MRI if secondary hypogonadism with very low LH/FSH or elevated prolactin 1
Critical Pitfalls to Avoid
- Never diagnose hypogonadism based on symptoms alone—biochemical confirmation with two low morning testosterone levels is mandatory 1, 3
- Never start TRT without confirming the patient does not desire fertility—exogenous testosterone suppresses spermatogenesis and causes prolonged azoospermia 1, 4
- Never use TRT in eugonadal men (normal testosterone levels), even for weight loss, muscle building, energy, or cognitive enhancement—this is explicitly contraindicated 1, 6
- Never assume age-related decline alone justifies treatment—the FDA specifically warns against TRT for "age-related hypogonadism" without confirmed deficiency and symptoms 2
- Never skip the distinction between primary and secondary hypogonadism—men with secondary hypogonadism can preserve fertility with gonadotropin therapy, while those with primary hypogonadism cannot 1, 7
Special Populations
Men Seeking Fertility
- Gonadotropin therapy (recombinant hCG + FSH) is mandatory—TRT is absolutely contraindicated 1, 4, 3
- Combined hCG and FSH therapy provides optimal outcomes for fertility preservation 1
Obesity-Associated Secondary Hypogonadism
- Attempt weight loss through low-calorie diets and regular exercise BEFORE initiating TRT, as this can improve testosterone levels without medication 5, 1
- If lifestyle modifications fail and biochemical hypogonadism persists with symptoms, then consider TRT 1