What are the criteria for a middle-aged man with hypogonadism (low testosterone levels), symptoms such as low libido, fatigue, or erectile dysfunction, and confirmed low testosterone levels to qualify for testosterone replacement therapy (TRT)?

Qualifying for Testosterone Replacement Therapy

To qualify for testosterone replacement therapy, a middle-aged man must have both biochemical confirmation of hypogonadism (morning total testosterone <300 ng/dL on two separate occasions) AND specific symptoms, particularly diminished libido and erectile dysfunction—not just fatigue or low energy alone. 1, 2

Diagnostic Requirements

Biochemical Confirmation

• Measure morning total testosterone (8-10 AM) on at least two separate occasions, with levels consistently below 300 ng/dL required to establish hypogonadism 1, 2, 3
• Measure free testosterone by equilibrium dialysis in addition to total testosterone, especially in men with obesity, diabetes, or borderline total testosterone levels, as SHBG alterations can mask true hypogonadism 1, 2
• Obtain sex hormone-binding globulin (SHBG) levels to distinguish true hypogonadism from SHBG-related decreases in total testosterone 1, 2

Determine Type of Hypogonadism

• Measure serum LH and FSH after confirming low testosterone to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism 1, 2
• Elevated LH/FSH with low testosterone indicates primary hypogonadism, while low or low-normal LH/FSH with low testosterone indicates secondary hypogonadism 2
• This distinction is critical: secondary hypogonadism patients can potentially achieve both fertility and normal testosterone with gonadotropin therapy, while primary hypogonadism patients can only receive testosterone therapy, which permanently compromises fertility 1, 2

Symptom Requirements

Symptoms That Justify Treatment

• Diminished libido and erectile dysfunction are the primary symptoms that warrant TRT, as these show the most reliable improvement with treatment (standardized mean difference 0.35) 1, 4
• Decreased spontaneous or morning erections are additional specific symptoms supporting treatment 1
• The 2024 TRAVERSE Sexual Function Study demonstrated that TRT improved sexual activity, hypogonadal symptoms, and sexual desire over 24 months in men with confirmed hypogonadism and low libido 5

Symptoms With Minimal or No Benefit from TRT

• Fatigue, low energy, depressed mood, reduced physical function, or cognitive complaints alone do NOT justify TRT, as testosterone produces little to no effect on these domains even in confirmed hypogonadism 1, 2, 4
• Energy and vitality improvements are minimal at best (standardized mean difference only 0.17), and depressive symptoms show less-than-small improvement (standardized mean difference -0.19) 1, 2
• The European Association of Urology explicitly recommends against testosterone therapy in eugonadal men, even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength 1, 2

Pre-Treatment Evaluation

Mandatory Baseline Testing

• Document baseline hematocrit or hemoglobin before initiating therapy, as hematocrit >54% is an absolute contraindication 2, 3
• Measure baseline PSA level and perform digital rectal examination in men over 40 years, with PSA >4.0 ng/mL requiring urologic evaluation before starting therapy 2
• Measure serum prolactin if testosterone is low or loss of libido is present 2
• Obtain fasting glucose to exclude diabetes, as testosterone therapy may improve insulin resistance and glycemic control in hypogonadal men with type 2 diabetes 1, 2

Fertility Assessment

• Explicitly confirm the patient does not desire fertility before starting TRT, as exogenous testosterone suppresses spermatogenesis and causes prolonged azoospermia 1, 2
• For men with secondary hypogonadism who desire fertility preservation, gonadotropin therapy (hCG plus FSH) is mandatory and testosterone is absolutely contraindicated 1, 2

Absolute Contraindications

TRT must not be initiated in men with: 1, 2, 4

• Active desire for fertility preservation
• Active or treated male breast cancer
• Hematocrit >54%
• Untreated severe obstructive sleep apnea
• Prostate cancer (though evidence is evolving, this remains a standard contraindication)

Common Pitfalls to Avoid

• Never diagnose hypogonadism based on symptoms alone without confirmed low testosterone levels, as approximately 20-30% of men receiving TRT in the United States do not have documented low testosterone before treatment initiation 1, 2
• Never use screening questionnaires or symptoms alone to diagnose hypogonadism due to lack of specificity 2
• Never assume age-related decline justifies treatment in men with normal testosterone levels, as the European Association of Urology explicitly warns against this practice 1, 2
• Never skip investigation for secondary causes of hypogonadism, as reversible conditions (obesity, sleep disorders, thyroid dysfunction, medications) must be addressed first 2

Alternative Approaches Before TRT

For Obesity-Associated Secondary Hypogonadism

• Attempt weight loss through low-calorie diets and regular exercise first, as this can improve testosterone levels without medication 1, 2
• Excessive aromatization of testosterone to estradiol in adipose tissue causes negative feedback on pituitary LH secretion, which can be reversed with weight loss 2

For Borderline Cases

• If total testosterone is borderline (231-346 ng/dL) but free testosterone is clearly low, this suggests true biochemical hypogonadism that would be missed by screening with total testosterone alone 2
• Address underlying causes first: evaluate for sleep disorders, thyroid dysfunction, anemia, vitamin D deficiency, metabolic syndrome, and medications that lower testosterone 2