How should I evaluate and manage a 55-year-old man with a total testosterone of 245 ng/dL (low)?

Evaluation and Management of Low Testosterone (245 ng/dL) in a 55-Year-Old Man

You must confirm the diagnosis with a second early-morning testosterone measurement before initiating any treatment, and you should measure LH, FSH, and free testosterone to distinguish primary from secondary hypogonadism and guide appropriate therapy. 1, 2

Diagnostic Confirmation Required

Your patient's single testosterone of 245 ng/dL falls below the diagnostic threshold of 300 ng/dL, but diagnosis requires two separate morning measurements (8-10 AM) on different days because of significant intra-individual variability and assay differences. 1, 2, 3 A single measurement is insufficient and can lead to inappropriate treatment in up to 25% of men. 1

Complete the Diagnostic Workup

Once you confirm persistently low testosterone with a second morning measurement:

• Measure LH and FSH to distinguish primary hypogonadism (elevated LH/FSH with low testosterone) from secondary hypogonadism (low or low-normal LH/FSH with low testosterone). 1, 2 This distinction is critical because it determines whether the patient can preserve fertility and whether gonadotropin therapy might be an option. 1

• Measure free testosterone by equilibrium dialysis (not direct immunoassay) along with sex hormone-binding globulin (SHBG), especially since your patient's total testosterone is in the borderline range. 1, 2, 4 In men with obesity or borderline total testosterone, low SHBG can artificially lower total testosterone while free testosterone remains normal, indicating functional rather than true hypogonadism. 1, 5

• Assess specific symptoms that justify treatment: diminished libido and erectile dysfunction are the primary indications. 1, 6, 2 Nonspecific symptoms like fatigue, low energy, or depressed mood show minimal or no proven benefit from testosterone therapy even with confirmed hypogonadism. 1, 6

Critical Pre-Treatment Evaluation

Before initiating testosterone therapy, you must:

• Assess fertility intentions. Testosterone therapy is absolutely contraindicated if the patient desires fertility preservation because it causes azoospermia. 1, 2 If fertility is a concern and he has secondary hypogonadism, gonadotropin therapy (hCG plus FSH) is mandatory instead. 1

• Document baseline hematocrit/hemoglobin. Hematocrit >54% is an absolute contraindication to starting therapy. 1, 2

• Perform prostate assessment in men over 40: digital rectal examination and baseline PSA measurement. 1, 2 PSA >4.0 ng/mL requires urologic evaluation and documented negative prostate biopsy before initiating therapy. 1

• Screen for contraindications: active breast cancer, untreated severe obstructive sleep apnea, recent cardiovascular events within 3-6 months, and hematocrit >54%. 1, 2

Treatment Selection and Expected Outcomes

If both biochemical hypogonadism and qualifying symptoms (diminished libido/erectile dysfunction) are confirmed, initiate transdermal testosterone gel 1.62% at 40.5 mg daily applied to shoulders and upper arms. 1, 2, 7 Transdermal preparations are preferred over intramuscular injections because they provide more stable day-to-day testosterone levels and carry lower risk of erythrocytosis (15.4% vs 43.8%). 1

Set Realistic Expectations

• Sexual function and libido: Small but significant improvements (standardized mean difference 0.35). 1, 2 This is the primary proven benefit.

• Energy, vitality, physical function, and cognition: Little to no effect even with confirmed hypogonadism. 1, 6, 2 The effect size for energy is minimal (SMD 0.17) and unlikely to be clinically meaningful. 1

• Depressive symptoms: Less-than-small improvements (SMD -0.19), and most studies showing benefit did not require depression at enrollment. 1

• Quality of life: Modest improvements, primarily driven by sexual function domains rather than energy or mood. 1, 2

Monitoring Protocol

• At 2-3 months: Measure testosterone levels (target mid-normal range 500-600 ng/dL), hematocrit, and PSA (if over 40). 1, 2 Adjust dose based on these results.

• Once stable: Monitor every 6-12 months with testosterone levels, hematocrit, and PSA. 1, 2

• Withhold treatment if hematocrit exceeds 54% and consider phlebotomy in high-risk cases. 1, 2

• At 12 months: If no improvement in sexual function despite achieving target testosterone levels, discontinue therapy to prevent unnecessary long-term exposure without benefit. 1, 2

Common Pitfalls to Avoid

• Do not diagnose hypogonadism on a single testosterone measurement. Two morning measurements are mandatory. 1, 2

• Do not test outside of morning hours (8-10 AM). Later measurements risk false-positive diagnoses due to diurnal variation. 1, 3

• Do not initiate treatment based solely on nonspecific symptoms like fatigue without confirmed sexual symptoms and biochemical hypogonadism. 1, 6

• Do not skip LH/FSH testing once low testosterone is confirmed, as the distinction between primary and secondary hypogonadism has critical treatment and fertility implications. 1, 2

• Do not use direct immunoassay for free testosterone; equilibrium dialysis or calculated values are required for accuracy. 1, 4, 8