What does a sex hormone‑binding globulin level of 74 nmol/L indicate and what causes its elevation?

What Does an SHBG of 74 nmol/L Mean?

An SHBG level of 74 nmol/L is elevated above the typical reference range (normal adult range approximately 20-60 nmol/L for men, 30-100 nmol/L for women), and this elevation reduces free testosterone availability by increasing the bound fraction of circulating sex steroids. 1

Clinical Significance of This Level

Impact on Hormone Availability

• SHBG binds testosterone with high affinity, reducing the amount of free testosterone available for biological activity. 1
• When SHBG levels increase to 74 nmol/L, a greater proportion of total testosterone becomes bound, decreasing the free and bioavailable testosterone fractions that can exert biological effects. 1
• This means you may have symptoms of testosterone deficiency even if your total testosterone appears normal on testing. 1

Compensatory Pituitary Response

• The pituitary gland primarily senses free testosterone levels rather than total testosterone when regulating hormonal feedback. 1
• Reduced free testosterone from elevated SHBG can trigger increased secretion of gonadotropins (FSH and LH) as the body attempts to compensate by stimulating more testosterone production. 1
• In functional hypothalamic amenorrhea patients, higher SHBG levels are associated with higher FSH levels. 1

Common Causes of Elevated SHBG

Endocrine Disorders

• Hyperthyroidism is a major cause of elevated SHBG, with synthesis of SHBG being directly influenced by thyroid hormones at the liver level. 2, 3
• In overt hyperthyroidism (Graves' disease), mean SHBG concentrations reach 141.6 ± 37.6 nmol/L compared to 48.3 ± 16.2 nmol/L in euthyroid individuals. 3
• Hypogonadism and androgen insensitivity syndromes elevate SHBG levels. 2

Hepatic Disease

• Hepatic cirrhosis and chronic liver disease significantly elevate SHBG, as the liver is the primary site of SHBG synthesis. 1, 2
• Chronic liver disease can disrupt the hypothalamic-pituitary axis, leading to altered gonadotropin levels including FSH. 1

Medications

• Estrogens (including oral contraceptives and hormone replacement therapy) markedly increase SHBG production. 1, 2
• Anticonvulsants elevate SHBG levels. 1, 2
• Thyroid hormone replacement therapy increases SHBG. 2

Other Factors

• Aging progressively increases SHBG levels in both men and women. 1
• Smoking is associated with elevated SHBG. 1
• HIV/AIDS elevates SHBG concentrations. 1

Critical Diagnostic Pitfall to Avoid

Relying solely on total testosterone measurements can miss cases of functional hypogonadism caused by elevated SHBG. 1 A person with SHBG of 74 nmol/L may have:

• Normal or even high total testosterone levels
• Low free testosterone causing symptoms
• A free testosterone index (total testosterone/SHBG ratio) <0.3, which indicates hypogonadism 1

Essential Next Steps

Required Testing

• Measure morning total testosterone (drawn between 8-10 AM) along with free testosterone by equilibrium dialysis to accurately assess your androgen status. 4, 1
• Check thyroid function tests (TSH, free T4) to evaluate for hyperthyroidism. 1, 3
• Obtain liver function tests to assess for hepatic disease. 1
• Consider HIV testing in appropriate clinical contexts. 1

Medication Review

• Review all current medications for those known to increase SHBG (estrogens, anticonvulsants, thyroid hormones). 1, 2

Treatment Approach

• Identifying and treating the underlying condition causing elevated SHBG is the most effective approach rather than attempting to lower SHBG directly. 1
• If hyperthyroidism is present, correct it appropriately. 1
• Manage liver disease if identified. 1
• Testosterone replacement may be appropriate if you have documented low free testosterone with symptoms (decreased libido, erectile dysfunction, reduced muscle mass, fatigue), even if total testosterone is normal. 1