What is the best course of management for a 36-year-old male with low morning (AM) testosterone levels, elevated Follicle-Stimulating Hormone (FSH) of 6.8, and Luteinizing Hormone (LH) of 5.3, presenting with potential hypogonadism or fertility concerns?

Management of a 36-Year-Old Male with Borderline-Normal Testosterone

This patient does NOT meet diagnostic criteria for hypogonadism and should NOT receive testosterone therapy at this time. 1

Why This Patient Does Not Qualify for Treatment

Testosterone level of 405 ng/dL is above the diagnostic threshold for hypogonadism (which requires levels <300 ng/dL on two separate morning measurements), and the FSH (6.8) and LH (5.3) are within normal range, indicating intact hypothalamic-pituitary-testicular axis function. 2, 1, 3

Critical Diagnostic Requirements Not Met

• Two separate morning testosterone measurements below 300 ng/dL are required to establish biochemical hypogonadism—this patient has only one measurement at 405 ng/dL, which is in the low-normal range but not diagnostic. 1, 3

• Specific hypogonadal symptoms must be present, particularly diminished libido and erectile dysfunction, which are the primary indications for testosterone therapy—the question does not indicate these symptoms are present. 1, 3

• The European Association of Urology explicitly recommends against testosterone therapy in eugonadal men (those with normal testosterone levels), even for complaints of fatigue, weight loss, or other nonspecific symptoms. 1

Recommended Diagnostic Workup

Step 1: Confirm Testosterone Status

• Repeat morning total testosterone measurement (8-10 AM) on at least one additional occasion to establish whether persistent low-normal testosterone exists, as single measurements are insufficient due to assay variability and diurnal fluctuation. 1, 3

• Measure free testosterone by equilibrium dialysis in addition to total testosterone, as this is essential when total testosterone is borderline—obesity increases sex hormone-binding globulin (SHBG), which can artificially lower total testosterone while free testosterone remains normal. 1, 3

• Obtain SHBG levels to calculate free androgen index (total testosterone/SHBG ratio) and distinguish true hypogonadism from SHBG-related decreases in total testosterone. 1

Step 2: Assess for Underlying Reversible Causes

Before considering any hormonal therapy, evaluate and address potentially reversible causes of low-normal testosterone:

• Obesity assessment and weight loss intervention—increased aromatization of testosterone to estradiol in adipose tissue causes estradiol-mediated negative feedback suppressing pituitary LH secretion. 1, 4 Weight loss through low-calorie diets and regular exercise can improve testosterone levels without medication. 1

• Screen for sleep disorders, particularly obstructive sleep apnea, which commonly causes secondary hypogonadism. 1

• Evaluate thyroid function (TSH, free T4) as hypothyroidism can present with fatigue and low testosterone. 1

• Check complete blood count to assess for anemia as a cause of fatigue. 1

• Measure vitamin D levels (25-hydroxyvitamin D), as deficiency is associated with low testosterone and fatigue. 1

• Assess for metabolic syndrome (fasting glucose, lipid panel, blood pressure, waist circumference) and cardiovascular risk factors. 1

Step 3: If Repeat Testing Confirms Low Testosterone (<300 ng/dL)

Only if repeat morning testosterone is confirmed below 300 ng/dL on two separate occasions should further hypogonadism workup proceed:

• The LH and FSH levels provided (LH 5.3, FSH 6.8) are in the normal range, which would indicate secondary (central) hypogonadism if testosterone were truly low—low or low-normal LH/FSH with low testosterone indicates hypothalamic-pituitary dysfunction. 1, 3

• Measure serum prolactin to investigate for hyperprolactinemia, which can cause secondary hypogonadism. 1

• Measure iron saturation to screen for hemochromatosis. 1

• Consider pituitary MRI if secondary hypogonadism is confirmed, to identify structural causes of hypothalamic/pituitary dysfunction. 1

Why Testosterone Therapy Would Be Inappropriate

Lack of Evidence for Benefit in This Population

• Testosterone therapy produces little to no effect on physical functioning, energy, vitality, or cognition even in men with confirmed hypogonadism (testosterone <300 ng/dL), with minimal effect sizes for energy and fatigue (standardized mean difference 0.17). 2, 1

• The primary proven benefit of testosterone therapy is improvement in sexual function and libido (standardized mean difference 0.35), which requires both confirmed biochemical hypogonadism AND specific sexual symptoms. 2, 1

• The American College of Physicians explicitly recommends against testosterone therapy in men with age-related low-normal testosterone to improve energy, vitality, or physical function, as it produces little to no effect on these outcomes. 2, 1

Significant Risks Without Clear Benefit

• Erythrocytosis risk is substantial, particularly with injectable testosterone (up to 44% risk), requiring monitoring and potential treatment discontinuation if hematocrit exceeds 54%. 1

• Potential cardiovascular risk with Peto odds ratio of 1.22 for cardiovascular events. 1

• Absolute contraindication to fertility—exogenous testosterone suppresses spermatogenesis and causes azoospermia, which may persist for months after discontinuation. 1, 5, 6 At age 36, fertility preservation is a critical consideration.

Alternative Management Strategy

Address Modifiable Risk Factors First

• Initiate structured weight loss program if BMI >25 kg/m², targeting 5-10% body weight reduction through caloric restriction and increased physical activity—this can improve testosterone levels by 50-100 ng/dL in obese men with secondary hypogonadism. 1

• Implement regular exercise program including both resistance training and aerobic exercise, which improves testosterone levels and addresses fatigue independently of hormonal changes. 1

• Optimize sleep hygiene and treat sleep disorders if identified, as sleep deprivation and sleep apnea significantly suppress testosterone production. 1

• Smoking cessation and alcohol moderation if applicable, as both negatively impact testosterone levels and sexual function. 1

If Sexual Dysfunction Is Present

• PDE5 inhibitors (sildenafil, tadalafil) are first-line treatment for erectile dysfunction and can be used effectively even with borderline testosterone levels—a minimal level of testosterone is required for complete effect, but 405 ng/dL is typically sufficient. 1

• Combination therapy with PDE5 inhibitors may be considered if erectile dysfunction persists despite lifestyle modifications, before considering testosterone therapy. 1

Common Pitfalls to Avoid

• Never diagnose hypogonadism based on symptoms alone without confirmed biochemical testing—approximately 20-30% of men receiving testosterone in the United States do not have documented low testosterone levels before treatment initiation, violating evidence-based guidelines. 1

• Never start testosterone therapy without confirming the patient does not desire fertility—this is irreversible in the short term and causes prolonged azoospermia. 1, 5

• Never assume age-related decline warrants treatment in a 36-year-old man—this patient is far too young for age-related hypogonadism, and secondary causes must be thoroughly investigated if true hypogonadism is confirmed. 1

• Never skip investigation for reversible causes such as obesity, sleep apnea, medications, or pituitary disease—these must be addressed first. 1

Follow-Up Plan

• Repeat morning testosterone measurement in 3 months after implementing lifestyle modifications, along with free testosterone and SHBG. 1, 3

• If repeat testing confirms testosterone <300 ng/dL on two occasions AND specific hypogonadal symptoms develop (particularly diminished libido and erectile dysfunction), then proceed with complete hypogonadism workup including prolactin, iron studies, and consideration of pituitary imaging. 1, 3

• Reevaluate in 6-12 months to assess response to lifestyle interventions and determine whether further hormonal evaluation is warranted based on symptom progression and repeat laboratory testing. 1