Sex Hormone Binding Globulin (SHBG): Factors Affecting Levels and Clinical Implications
Factors That Increase SHBG Levels
The primary factors that increase SHBG levels include medications (anticonvulsants, estrogens, thyroid hormones), hyperthyroidism, hepatic disease, aging, smoking, and HIV/AIDS. 1
Medications
- Estrogens and estrogen-containing medications: Oral contraceptives containing ethinyl estradiol significantly increase SHBG synthesis 2
- Anticonvulsants
- Thyroid hormone replacement therapy
Medical Conditions
- Hyperthyroidism
- Hepatic disease/liver disorders
- HIV/AIDS
- Anorexia and eating disorders 3
- Acute and critical illness 3
Physiological Factors
- Advanced age: Each year of aging is associated with approximately 0.46 nmol/L increase in SHBG 4
- Smoking
- Endurance exercise 3
- Regular coffee consumption (≥2 cups/day) 5
- Physical activity 5
Factors That Decrease SHBG Levels
Obesity, insulin resistance, metabolic syndrome, polycystic ovary syndrome, and certain medications (growth hormone, glucocorticoids, testosterone, anabolic steroids) are the main factors that decrease SHBG levels. 3, 1
Medications
- Growth hormone
- Glucocorticoids
- Testosterone and anabolic steroids
Medical Conditions
- Obesity: Each unit increase in BMI is associated with a 1.26 nmol/L decrease in SHBG 4
- Insulin resistance/hyperinsulinemia 6
- Polycystic ovary syndrome (PCOS)
- Cushing syndrome 3
- Hypothyroidism
- Acromegaly
- Nephrotic syndrome
Physiological Factors
- High BMI: The inverse BMI-SHBG relationship is especially strong when BMI is below 30 5
- Increased caloric intake 7
Clinical Implications of Altered SHBG Levels
Impact on Hormone Availability
- SHBG binds to sex hormones (particularly testosterone and estradiol), regulating their bioavailability
- High SHBG levels reduce free testosterone, potentially contributing to symptoms of hypogonadism 1
- Low SHBG levels increase free testosterone, potentially contributing to hyperandrogenism
Diagnostic Considerations
- SHBG is a key factor in interpreting total testosterone measurements 4
- In obese men, low SHBG can lead to low total testosterone despite normal free testosterone levels 4
- SHBG is an important marker in the diagnosis of PCOS and hyperandrogenism 3
Associated Conditions
Low SHBG levels are associated with:
- Metabolic syndrome
- Type 2 diabetes
- PCOS
- Cardiovascular disease risk 8
High SHBG levels are associated with:
Clinical Pearls and Pitfalls
- The effect of obesity on decreasing SHBG is 2-3 times stronger than the effect of aging on increasing SHBG 4
- When evaluating testosterone levels, consider measuring both total and free testosterone, especially in patients with conditions that alter SHBG levels
- SHBG changes can occur independently of androgen levels, particularly in conditions like precocious adrenarche 7
- In women taking oral contraceptives, SHBG levels can increase significantly, affecting interpretation of androgen measurements 2
- When evaluating hyperandrogenic conditions, consider SHBG levels as they may explain discrepancies between clinical symptoms and measured total hormone levels
Monitoring Recommendations
- Consider measuring SHBG when evaluating:
- Suspected hypogonadism in men
- Hyperandrogenic states in women
- Patients with metabolic syndrome or obesity
- Patients on medications known to affect SHBG levels
- Patients with unexplained changes in sex hormone-dependent conditions
By understanding the factors that influence SHBG levels, clinicians can better interpret hormone measurements and identify underlying conditions that may be contributing to patients' symptoms.