What is the initial workup and treatment for a patient with suspected low testosterone (hypogonadism)?

Initial Workup and Treatment for Suspected Low Testosterone (Hypogonadism)

The diagnosis of low testosterone should only be made after two total testosterone measurements are taken on separate occasions with both conducted in an early morning fashion, and only when patients have low total testosterone levels combined with symptoms and/or signs of testosterone deficiency. 1

Diagnostic Workup

Initial Laboratory Assessment

• Measure morning total testosterone level, using a cutoff below 300 ng/dL as a reasonable threshold to support the diagnosis of low testosterone 1
• Confirm the diagnosis with a second morning total testosterone measurement on a separate day 1, 2
• If total testosterone is near the lower limit of normal or if conditions that alter sex hormone-binding globulin are present, consider measuring free testosterone or bioavailable testosterone 3, 4
• Measure luteinizing hormone (LH) levels to help establish whether hypogonadism is primary (testicular) or secondary (pituitary/hypothalamic) 3, 5
• Consider measuring serum prolactin in patients with low testosterone combined with low or low/normal LH levels 5
• Consider pituitary MRI for patients with total testosterone <150 ng/dL and low/normal LH regardless of prolactin levels 5

Clinical Assessment

• Evaluate for symptoms and signs of testosterone deficiency, which may include 1, 5, 6:
  • Reduced energy and endurance
  • Fatigue
  • Depression
  • Poor concentration
  • Reduced sex drive
  • Erectile dysfunction
  • Decreased muscle mass
  • Increased body fat
• Perform digital rectal examination and measure PSA before initiating treatment 5
• Assess cardiovascular disease risk factors 5
• Measure hemoglobin/hematocrit at baseline to monitor for polycythemia 5
• Evaluate for sleep apnea by history taking 5
• Conduct a reproductive health evaluation in men interested in fertility before treatment 5

Treatment Approach

Initiation of Testosterone Replacement Therapy

• Start testosterone replacement therapy only when both low testosterone levels and symptoms/signs of hypogonadism are present 1, 2
• The recommended starting dose of testosterone gel 1.62% is 40.5 mg of testosterone (2 pump actuations) applied topically once daily in the morning to the shoulders and upper arms 2
• Alternative formulations include intramuscular injections, patches, and other topical preparations, with selection based on patient preference, cost, and specific properties 6

Dose Adjustment

• Titrate dose based on pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment 2
• Adjust dose between a minimum of 20.25 mg (1 pump actuation) and a maximum of 81 mg (4 pump actuations) for gel formulations 2
• Target testosterone levels in the mid to upper-normal range for optimal response, but avoid supraphysiologic levels 5

Monitoring

• Schedule first follow-up visit at 1-2 months to assess efficacy and consider dose adjustments 5
• Monitor at 3-6 month intervals for the first year and yearly thereafter 5
• At each visit, assess 5:
  • Symptomatic response to treatment
  • Voiding symptoms
  • Sleep apnea symptoms
  • Digital rectal examination
  • Serum testosterone levels
  • PSA levels
  • Hematocrit or hemoglobin

Contraindications and Precautions

Absolute Contraindications

• Men with breast cancer or known/suspected prostate cancer 2
• Pregnant women (testosterone may cause fetal harm) 2
• Uncontrolled congestive heart failure 7, 8
• Recent myocardial infarction or stroke (within 6 months) 8
• Thrombophilia 8

Relative Contraindications/Cautions

• Severe lower urinary tract symptoms 2, 8
• Elevated hematocrit 2, 8
• Untreated severe obstructive sleep apnea 8
• Men planning fertility in the near term (testosterone therapy will greatly compromise fertility) 5, 9
• Use cautiously in men with congestive heart failure or renal insufficiency due to potential fluid retention 5

Alternative Treatments

• For men wishing to preserve fertility, consider gonadotropin therapy instead of testosterone replacement 9
• Clomiphene citrate and tamoxifen may be alternatives for functional central hypogonadism, though their use is off-label 9

Common Pitfalls to Avoid

• Treating based on symptoms alone without laboratory confirmation of low testosterone levels 5
• Failing to distinguish between primary and secondary hypogonadism, which require different management approaches 3
• Not considering other causes of similar symptoms before attributing them to testosterone deficiency 3
• Not monitoring for potential adverse effects such as polycythemia, prostate issues, and cardiovascular events 5, 2