What is the management approach for a patient with normal Sex Hormone Binding Globulin (SHBG) but reduced total morning testosterone levels?

Management of Normal SHBG with Reduced Total Morning Testosterone

For patients with normal sex hormone-binding globulin (SHBG) but reduced total morning testosterone levels, free testosterone measurement is essential to determine if true testosterone deficiency exists, as normal SHBG with low total testosterone may indicate normal free testosterone levels in some cases. 1

Diagnostic Approach

• Confirm low total testosterone with a second morning measurement (between 8-10 AM) as testosterone levels show diurnal variation with highest levels in the morning 1
• Measure free testosterone levels by equilibrium dialysis to determine if true testosterone deficiency exists despite normal SHBG 1
• Measure serum luteinizing hormone (LH) levels to help establish the etiology of testosterone deficiency (primary vs. secondary hypogonadism) 1
• Clinical diagnosis of testosterone deficiency requires both consistently low total testosterone (<300 ng/dL on at least two separate morning measurements) AND presence of symptoms/signs 1

Clinical Assessment

• Document symptoms associated with low testosterone:

  • Reduced energy, endurance, physical performance 1
  • Fatigue, depression, reduced motivation 1
  • Poor concentration, impaired memory 1
  • Reduced sex drive, changes in erectile function 1
  • Infertility 1

• Perform targeted physical examination for signs of low testosterone:

  • Body habitus and virilization status 1
  • Body mass index/waist circumference 1
  • Gynecomastia 1
  • Testicular evaluation (size, consistency) 1
  • Prostate examination 1

Special Considerations

• In obese patients, low total testosterone with normal SHBG often occurs due to increased aromatization of testosterone to estradiol in adipose tissue 1
• Consider measuring total testosterone in patients with specific risk factors even without symptoms:
  • Unexplained anemia, bone density loss 1
  • Diabetes 1
  • Exposure to chemotherapy or testicular radiation 1
  • HIV/AIDS 1
  • Chronic narcotic or corticosteroid use 1
  • Male infertility 1
  • Pituitary dysfunction 1

Treatment Approach

• If free testosterone is normal despite low total testosterone, testosterone replacement therapy is not indicated 1
• If free testosterone is confirmed low on at least two separate assessments, consider testosterone replacement therapy 1
• Treatment options include:
  • Transdermal preparations (gel, patch) - preferred for most patients due to stable day-to-day levels 1
  • Intramuscular injections - beneficial for patients with reduced personal disease-management skills or resources 1
  • Implantable testosterone pellets - longer-term alternative but requires implantation procedure 1

Monitoring

• After initiating treatment, monitor testosterone levels at 2-3 months to ensure normal serum testosterone concentrations are achieved 1
• Target testosterone levels in the mid-normal range with any approved formulation 2

Pitfalls and Caveats

• Relying solely on total testosterone to exclude hypogonadism may miss cases of true testosterone deficiency, especially in men over 60 years old 3
• Morning and afternoon testosterone levels may not differ significantly in older men, but younger men (<30 years) show more significant diurnal variations 4, 5
• Screening questionnaires are not recommended for identifying candidates for testosterone therapy due to variable specificity and sensitivity 1
• Do not start testosterone therapy in patients with:
  • Breast or prostate cancer 2
  • Palpable prostate nodule or PSA >4 ng/ml without urological evaluation 2
  • Hematocrit >50% 2
  • Untreated severe obstructive sleep apnea 2
  • Severe lower urinary tract symptoms 2
  • Uncontrolled heart failure 2