When is ordering sex hormone-binding globulin (SHBG) recommended?

Sex Hormone Binding Globulin (SHBG) Testing: Clinical Indications and Utility

Sex hormone binding globulin (SHBG) testing is essential for accurate assessment of hormonal status in patients with suspected hormonal disorders, particularly when evaluating testosterone bioavailability, metabolic abnormalities, and polycystic ovary syndrome (PCOS). 1

Primary Clinical Indications for SHBG Testing

1. Evaluation of Testosterone Status

• Essential in male patients with erectile dysfunction
  • SHBG is crucial when assessing total testosterone levels, as high SHBG is the most common cause of normal total testosterone with low free testosterone 1
  • Particularly important in obese patients or those with conditions affecting SHBG levels 1
  • Helps distinguish between bioavailable and bound testosterone

2. Assessment of PCOS

• Critical biomarker for PCOS diagnosis and monitoring
  • Lower serum SHBG levels are strongly associated with increased risk of PCOS 2
  • SHBG levels are routinely collected in PCOS clinical trials to monitor treatment effectiveness 3
  • Serves as an indicator of hyperandrogenism in women 2

3. Metabolic Disorders Evaluation

• Marker for insulin resistance and metabolic syndrome
  • Low SHBG levels correlate with insulin resistance and hyperinsulinism 4
  • Associated with increased risk for type 2 diabetes 4
  • Negative correlation with body mass index and fasting insulin levels in hirsute patients 4

4. Monitoring Treatment Response

• Valuable for assessing therapeutic interventions
  • SHBG levels increase during oral estrogen administration 4
  • Used to monitor response to anti-obesity medications (orlistat, exenatide, liraglutide) in PCOS 3, 1
  • Helps evaluate efficacy of metformin therapy in improving insulin sensitivity 1

Special Clinical Scenarios

Thyroid Dysfunction

• SHBG levels increase in thyrotoxicosis but remain normal in syndromes of abnormal thyroid hormone transport or resistance 4
• Useful for differentiating true hyperthyroidism from other conditions with elevated thyroid hormones

Reproductive Health Assessment

• Important in female cancer survivors at risk for primary or premature ovarian failure 3
• Helps evaluate gonadal function in patients who received gonadotoxic therapy 3

Cardiovascular Risk Assessment

• In men, SHBG levels positively correlate with high-density lipoprotein cholesterol 4
• Low SHBG associated with increased cardiovascular risk in postmenopausal women 4

Interpretation Considerations

Age and Gender Variations

• SHBG levels vary widely among both younger and older men 5
  • Mean SHBG is significantly higher in men ≥55 years (36.6±15.8 nmol/L) compared to men ≤54 years (27.7±13.3 nmol/L) 5
  • Up to 20-fold difference between lowest and highest values in clinical populations 5

Conditions Affecting SHBG Levels

• Factors that decrease SHBG:

  • Obesity
  • Insulin resistance
  • Hyperinsulinemia
  • Androgens
  • Glucocorticoids

• Factors that increase SHBG:

  • Estrogens
  • Thyroid hormones
  • Advanced age
  • Cirrhosis
  • HIV infection

Clinical Pitfalls to Avoid

• Relying solely on total testosterone without SHBG measurement

  • May miss testosterone deficiency in patients with high SHBG 1
  • Could lead to incorrect diagnosis and inappropriate treatment

• Ignoring SHBG in obese patients

  • Obesity increases aromatization of testosterone to estradiol 1
  • SHBG is particularly important for accurate assessment in these patients

• Failing to consider SHBG polymorphisms

  • Genetic variations can influence SHBG levels and activity 6
  • May affect interpretation of hormone test results

Conclusion

SHBG testing provides valuable clinical information beyond simple sex hormone assessment. It serves as an important biomarker for metabolic disorders, helps accurately interpret testosterone levels, aids in PCOS diagnosis and management, and contributes to cardiovascular risk assessment. The wide variability in SHBG levels among individuals underscores the importance of including this test when evaluating hormonal status, particularly in patients with suspected endocrine or metabolic disorders.