What treatment options are recommended for a 25-year-old male with hypogonadism (low testosterone), as indicated by total testosterone levels of 262, free testosterone levels of 45, and bioavailable testosterone levels of 105, along with slightly elevated prolactin levels of 8.4?

Management of Hypogonadism in a 25-Year-Old Male

This 25-year-old male has confirmed secondary (hypogonadotropic) hypogonadism based on low testosterone (262 ng/dL) with inappropriately low-normal FSH (0.8) and LH (2.2), and requires investigation for underlying causes before initiating treatment, as fertility preservation is critical at this age. 1

Critical Diagnostic Considerations

Confirm the Diagnosis

• Repeat morning testosterone measurement (8-10 AM) on a separate occasion to confirm persistent hypogonadism, as diagnosis requires two low measurements 1, 2
• The current total testosterone of 262 ng/dL is below the diagnostic threshold of 300 ng/dL used by most guidelines 2, 3
• Free testosterone (45 pg/mL) and bioavailable testosterone (105 ng/dL) are also low, supporting the diagnosis 2

Identify Secondary Hypogonadism Etiology

The combination of low testosterone with low-normal FSH (0.8) and LH (2.2) indicates secondary (hypothalamic-pituitary) hypogonadism, NOT primary testicular failure 1, 2

This distinction is absolutely critical because:

• Secondary hypogonadism patients can potentially achieve both fertility restoration AND normal testosterone with appropriate treatment 1
• Primary hypogonadism patients can only receive testosterone therapy, which permanently compromises fertility 1

Mandatory Workup Before Treatment

You must investigate for reversible causes of secondary hypogonadism: 1

• MRI pituitary with contrast - Rule out pituitary adenoma (especially prolactinoma given prolactin 8.4 ng/mL is at upper normal limit) 4
• Detailed medication history - Opioids, glucocorticoids, and anabolic steroids suppress the HPG axis 1
• Assess for obesity/metabolic syndrome - Check BMI and waist circumference, as weight loss can restore testosterone in obesity-associated hypogonadism 1, 2
• Screen for chronic illnesses - Diabetes, COPD, inflammatory diseases, and chronic infections are associated with secondary hypogonadism 5
• IGF-1 is low at 151 - Consider growth hormone deficiency evaluation, as GHD frequently coexists with hypogonadism in pituitary disease 4

Treatment Algorithm

If Fertility is Desired (Age 25 Makes This Presumptive)

Testosterone therapy is ABSOLUTELY CONTRAINDICATED in men seeking fertility preservation 2, 6

First-line treatment: Gonadotropin therapy 1, 2

• Recombinant human chorionic gonadotropin (hCG) plus FSH provides optimal outcomes for both testosterone normalization AND spermatogenesis 2
• This approach stimulates the testes directly, bypassing the suppressed pituitary 1
• Combined hCG/FSH therapy can restore both testosterone levels and fertility potential 2

If Fertility is NOT a Concern (After Counseling)

Only after confirming the patient does not desire fertility now or in the future should testosterone replacement therapy be considered 2, 6

Preferred Initial Regimen

Transdermal testosterone gel 1.62% at 40.5 mg daily is the recommended first-line formulation 2

• Provides more stable day-to-day testosterone levels compared to injections 2, 3
• Reduces risk of erythrocytosis compared to intramuscular preparations 2

Alternative: Intramuscular Testosterone (If Cost is Limiting)

Testosterone cypionate 50-100 mg IM every 2 weeks 2, 6

• Annual cost approximately $156 vs. $2,135 for transdermal 2
• FDA-approved dosing is 50-400 mg every 2-4 weeks 6
• Common pitfall: Weekly dosing exceeds standard practice and increases risk of supraphysiologic levels and erythrocytosis 2

Target Testosterone Levels

Aim for mid-normal range: 450-600 ng/dL 2, 3

• For injectable testosterone: measure midway between injections 2, 3
• For transdermal: can measure anytime, peak occurs 6-8 hours after application 3

Monitoring Schedule

• Check testosterone at 2-3 months after initiation or dose change 2, 3
• Once stable, monitor every 6-12 months 2, 3
• Monitor hematocrit periodically; withhold treatment if >54% 2
• Monitor PSA in men over 40 years (not applicable here) 2

Expected Outcomes with Testosterone Therapy

Realistic expectations must be discussed: 1, 2

• Small but significant improvements in sexual function and libido 1, 2
• Little to no effect on energy, vitality, physical function, or cognition 1
• Improvements in body composition, fasting glucose, and lipid profile 2
• Quality of life improvements are modest at best 2

Reassessment Strategy

Reevaluate symptoms at 12 months 1

• Discontinue testosterone if no improvement in sexual function after 12 months 1
• This prevents unnecessary long-term exposure to potential risks without benefit 1

Absolute Contraindications to Testosterone Therapy

Do NOT initiate testosterone if: 2, 6, 7, 8

• Patient is actively seeking fertility (MOST IMPORTANT at age 25) 2, 6
• Breast or prostate cancer 2, 7, 8
• Hematocrit >50% 7, 8
• Untreated severe obstructive sleep apnea 7, 8
• Uncontrolled heart failure 7, 8

Critical Pitfalls to Avoid

1. Never start testosterone without confirming the patient does not desire fertility - This is the single most important consideration in a 25-year-old 2, 6

2. Never diagnose hypogonadism based on symptoms alone - Screening questionnaires lack specificity and should not be used for diagnosis 1

3. Never assume age-related decline in a 25-year-old - This patient is far too young for late-onset hypogonadism; an underlying pathology must be identified 1, 9

4. Never skip the investigation for secondary causes - Reversible conditions (obesity, medications, pituitary disease) must be addressed first 1, 2

5. Do not use testosterone therapy in eugonadal men - The European Association of Urology explicitly recommends against this, even for weight loss or metabolic improvement 2