Can Symptomatic Hypogonadism with Testosterone 455 ng/dL Be Treated?
No, testosterone replacement therapy should not be initiated in a symptomatic man with a testosterone level of 455 ng/dL, as this level falls within the normal physiologic range and treatment is only indicated when both biochemical deficiency (testosterone <300 ng/dL) and clinical symptoms are present. 1, 2
Why Treatment Is Not Indicated
Biochemical criteria are not met. The American Urological Association defines hypogonadism as testosterone <300 ng/dL confirmed on two separate morning measurements, and this patient's level of 455 ng/dL exceeds this threshold. 1, 3 The FDA labeling for testosterone products explicitly states they are approved only for "deficiency or absence of endogenous testosterone," not for men with normal levels. 4
The treatment goal cannot be achieved. Testosterone replacement therapy aims to normalize levels to 450-600 ng/dL—this patient is already at the lower end of the target range. 1, 3 Since therapy cannot improve upon normal physiology, the risk-benefit ratio becomes entirely unfavorable. 2
Treatment provides no benefit in eugonadal men. The American Urological Association and European Association of Urology explicitly recommend against initiating testosterone therapy in eugonadal individuals. 3 The Princeton III Consensus states that testosterone >350 ng/dL typically does not require replacement therapy. 3
Risks Without Benefits
When testosterone levels are already normal, treatment exposes patients to significant risks without potential for symptomatic improvement:
Infertility: Exogenous testosterone completely suppresses sperm production through negative feedback on the hypothalamic-pituitary-gonadal axis, causing severe oligospermia or azoospermia. 2
Cardiovascular concerns: Current literature cannot definitively prove safety regarding major adverse cardiovascular events, and patients with recent cardiovascular events (within 3-6 months) should not receive therapy. 1, 2
Polycythemia: Testosterone increases hemoglobin/hematocrit, requiring regular monitoring and potential phlebotomy if hematocrit exceeds 50%. 2
Prostate monitoring burden: Men over 40 require PSA monitoring with specific thresholds triggering urologic evaluation. 2
Alternative Approach for This Patient
Address the underlying cause of symptoms. Since testosterone deficiency is not the issue, investigate other etiologies:
Evaluate for high systemic disease burden. Men with multiple comorbidities (cardiovascular disease, diabetes, obesity, sleep apnea, anxiety, neurologic conditions) are less likely to have symptomatic improvement even with true testosterone deficiency. 5 A patient with normal testosterone and persistent symptoms likely has symptoms driven by these other conditions.
Recommend lifestyle modifications. Weight loss and increased physical activity can improve energy, sexual function, and metabolic parameters regardless of testosterone status. 6, 1 For a patient with high BMI and normal testosterone, weight loss counseling addresses cardiovascular risk reduction. 2
Screen for specific treatable conditions: Sleep apnea, depression, diabetes, and cardiovascular disease all cause fatigue, erectile dysfunction, and decreased libido—the same symptoms attributed to hypogonadism. 5
Common Clinical Pitfall
Approximately 20-25% of men receiving testosterone therapy do not meet diagnostic criteria for testosterone deficiency, highlighting widespread inappropriate prescribing. 3 The evidence supports treating deficiency to normal levels, not pushing normal to supraphysiologic ranges. 2 Starting therapy with normal baseline levels guarantees that testosterone will not provide symptomatic relief. 2