What are the next steps for an adult male with hypogonadism (Low Testosterone Levels)?

Management of Adult Male with Total Testosterone 235 ng/dL

You need to confirm persistent biochemical hypogonadism with a repeat morning testosterone measurement (8-10 AM), measure free testosterone by equilibrium dialysis and SHBG, then assess for specific hypogonadal symptoms—particularly diminished libido and erectile dysfunction—before considering testosterone replacement therapy. 1

Immediate Diagnostic Steps

Confirm the Diagnosis

• Repeat morning total testosterone between 8 AM and 10 AM on a separate occasion to confirm levels consistently <300 ng/dL, as single measurements are insufficient due to assay variability and diurnal fluctuation 1, 2
• Measure free testosterone by equilibrium dialysis in addition to total testosterone, as this is essential when total testosterone is borderline (235 ng/dL falls in this range) 1
• Obtain SHBG levels to distinguish true hypogonadism from low SHBG-related decreases in total testosterone 1

Determine Type of Hypogonadism

• Measure serum LH and FSH after confirming low testosterone to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1
• Elevated LH/FSH with low testosterone indicates primary hypogonadism 1
• Low or low-normal LH/FSH with low testosterone indicates secondary hypogonadism 1, 3
• This distinction has critical treatment implications, particularly for fertility preservation 1, 3

Symptom Assessment

Primary Symptoms Warranting Treatment

The most important symptoms to assess are:

• Diminished libido (decreased sexual desire)—the most specific symptom for hypogonadism 1, 2
• Erectile dysfunction, especially if PDE5 inhibitor therapy has failed 1, 2
• Decreased spontaneous or morning erections 2

Symptoms with Minimal Benefit from Treatment

Do not expect meaningful improvements in the following, even with confirmed hypogonadism:

• Physical functioning, energy, or vitality (effect size only 0.17) 1
• Depressive symptoms (effect size only -0.19) 1
• Cognitive function 1

The American College of Physicians explicitly recommends against testosterone treatment to improve energy, vitality, physical function, or cognition alone 2

Treatment Decision Algorithm

If Confirmed Hypogonadism with Sexual Symptoms

Step 1: Assess Fertility Desires

• If the patient desires fertility preservation, testosterone replacement therapy is absolutely contraindicated 1, 3
• For secondary hypogonadism with fertility concerns, use gonadotropin therapy (recombinant hCG plus FSH) instead 1, 3
• Exogenous testosterone suppresses spermatogenesis and causes prolonged azoospermia 1

Step 2: Rule Out Contraindications Absolute contraindications include:

• Active desire for fertility preservation 1, 3
• Active or treated male breast cancer 1
• Hematocrit >54% 1, 3
• Untreated severe obstructive sleep apnea 1
• Recent cardiovascular events within 3-6 months 1

Step 3: Address Reversible Causes First Before initiating testosterone therapy:

• Attempt weight loss through low-calorie diets and regular exercise if obesity is present, as this can improve testosterone levels without medication 1, 3
• Optimize diabetes management if present 1
• Treat sleep apnea if identified 1
• Discontinue offending medications 3

Step 4: Select Testosterone Formulation

For initial therapy, choose based on patient preference and cost:

Transdermal testosterone gel (preferred first-line):

• Dose: 40.5 mg daily (1.62% gel) 1
• Advantages: More stable day-to-day testosterone levels, lower erythrocytosis risk 1
• Disadvantages: Annual cost ~$2,135 4, 1
• Patient preference: 71% prefer gel for convenience, ease of use, and non-staining of clothes 4, 1

Intramuscular testosterone cypionate or enanthate (more economical):

• Dose: 100-200 mg every 2 weeks or 50 mg weekly 1, 3
• Advantages: Annual cost ~$156, similar efficacy 4, 1
• Disadvantages: Higher erythrocytosis risk, fluctuating levels (peak days 2-5, return to baseline days 10-14) 1

Monitoring Requirements

Initial Monitoring

• Testosterone levels at 2-3 months after treatment initiation or any dose change 1
• For injectable testosterone, measure levels midway between injections (days 5-7), targeting mid-normal values of 500-600 ng/dL 1
• Hematocrit at each visit—withhold treatment if >54% and consider phlebotomy 1, 3

Long-Term Monitoring

• Once stable levels confirmed, monitor every 6-12 months 1
• PSA levels in men over 40 years—refer for urologic evaluation if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 1
• Digital rectal examination at each visit to assess for prostate abnormalities 1

Treatment Response Assessment

• Reevaluate symptoms at 12 months 1
• Discontinue testosterone if no improvement in sexual function is seen, to prevent unnecessary long-term exposure to potential risks without benefit 1

Expected Treatment Outcomes

Realistic expectations to discuss with the patient:

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 1, 3
• Modest quality of life improvements, primarily in sexual function domains 1, 3
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition 1, 3
• Potential improvements in metabolic parameters (fasting glucose, insulin resistance, triglycerides, HDL cholesterol) 1

Critical Pitfalls to Avoid

• Never start testosterone without confirming the patient does not desire fertility, as this causes irreversible suppression of spermatogenesis 1
• Never diagnose hypogonadism based on symptoms alone without confirmed biochemical testing on two separate occasions 1
• Never assume age-related decline justifies treatment without specific sexual symptoms—the European Association of Urology explicitly recommends against testosterone therapy in eugonadal men, even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength 1
• Never draw testosterone levels at peak (days 2-5) or trough (days 13-14) for injectable formulations, as this leads to inappropriate dosing decisions 1
• Never continue treatment beyond 12 months without documented improvement in sexual function 1