What is the next step in managing a 39-year-old male with mildly decreased testosterone levels, ranging from 210 to 295 ng/dL (nanograms per deciliter), and potential symptoms of hypogonadism?

Next Step: Measure Serum LH and FSH Levels

The next step is to measure serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to distinguish between primary (testicular) and secondary (hypothalamic-pituitary) hypogonadism. 1

Diagnostic Confirmation

Your patient has two testosterone measurements (210 ng/dL and 295 ng/dL), both below the diagnostic threshold of 300 ng/dL that defines hypogonadism. 1 The AUA guideline requires two separate early morning testosterone measurements below 300 ng/dL to establish biochemical hypogonadism, which this patient meets. 1

However, diagnosis requires both low testosterone AND symptoms/signs of testosterone deficiency. 1 You must assess for:

• Sexual symptoms: Reduced libido, erectile dysfunction, decreased spontaneous erections 1, 2
• Physical symptoms: Reduced energy, diminished work/physical performance, fatigue, reduced muscle mass 1, 2
• Psychological symptoms: Depression, reduced motivation, poor concentration, impaired memory, irritability 1
• Physical signs: Body habitus, virilization status (body hair patterns), gynecomastia, testicular size/consistency 1

Critical Next Step: Gonadotropin Measurement

Measuring LH and FSH is mandatory to determine the etiology and guide treatment selection. 1, 2 This distinction has critical implications:

• Low or low-normal LH/FSH = Secondary (hypothalamic-pituitary) hypogonadism 1, 2
• Elevated LH/FSH = Primary (testicular) hypogonadism 1, 2

If Secondary Hypogonadism (Low/Normal LH and FSH):

1. Measure serum prolactin to screen for hyperprolactinemia and potential pituitary tumors 1
2. Consider pituitary MRI if testosterone <150 ng/dL with low/normal LH, as non-secreting adenomas may be present 1
3. Evaluate for reversible causes: obesity, diabetes, sleep apnea, chronic opioid use, corticosteroid use 1
4. If fertility is desired: Gonadotropin therapy (hCG plus FSH) is mandatory—testosterone therapy is absolutely contraindicated as it causes azoospermia 1, 2

If Primary Hypogonadism (Elevated LH and FSH):

1. Assess fertility status with testicular exam and consider semen analysis 1
2. Genetic testing (karyotype, Y-chromosome microdeletions) if severe oligospermia or azoospermia 1
3. Testosterone replacement is appropriate if symptomatic, but fertility cannot be preserved 2

Additional Baseline Testing Before Treatment

If hypogonadism is confirmed and treatment is considered:

• Hemoglobin/hematocrit: Document baseline to monitor for erythrocytosis (withhold if hematocrit >54%) 1, 2
• PSA and digital rectal exam in men >40 years: Rule out prostate cancer 1, 2
• Lipid panel and cardiovascular risk assessment: Assess ASCVD risk factors 1
• Free testosterone by equilibrium dialysis if total testosterone is borderline, especially in obesity 1, 2
• SHBG levels: Distinguish true hypogonadism from low SHBG-related reductions 1, 2

Weight Loss as First-Line for Obesity-Related Hypogonadism

At age 39, if this patient has obesity-associated secondary hypogonadism (low/normal LH and FSH), attempt weight loss through low-calorie diets and regular exercise BEFORE initiating testosterone, as this can improve testosterone levels without medication. 1, 2 Obesity causes increased aromatization of testosterone to estradiol in adipose tissue, with subsequent estradiol-mediated negative feedback suppressing LH secretion. 1

Common Pitfalls to Avoid

• Never start testosterone without confirming the patient does not desire fertility 2—exogenous testosterone suppresses spermatogenesis and causes prolonged azoospermia 1, 2
• Never diagnose hypogonadism based on symptoms alone without confirmed low testosterone 1
• Never assume age-related decline in a 39-year-old man—investigate for secondary causes 2
• Never skip gonadotropin measurement—the distinction between primary and secondary hypogonadism determines treatment options and fertility preservation strategies 1, 2

Expected Treatment Outcomes (If Indicated)

If testosterone therapy is ultimately appropriate, set realistic expectations: 2

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 2
• Little to no effect on physical functioning, energy, vitality, or cognition 2
• Modest quality of life improvements, primarily in sexual function domains 2