When should I order a serum sex hormone‑binding globulin (SHBG) level and how do I interpret low or high results in the context of hormonal imbalance?

When to Order SHBG and How to Interpret Results

Order SHBG whenever you measure total testosterone in any patient with suspected hormonal imbalance, erectile dysfunction, hirsutism, or symptoms of androgen deficiency or excess—total testosterone alone is insufficient and can miss functional hypogonadism or hyperandrogenism. 1

Primary Indications for SHBG Testing

In Men

• All men with erectile dysfunction should have both testosterone and SHBG measured concurrently, especially those who have failed phosphodiesterase-5 inhibitor therapy 1
• Men presenting with decreased libido, erectile dysfunction, reduced muscle mass, or fatigue require morning total testosterone (8-10 AM) plus SHBG to calculate free testosterone 1
• Any evaluation for hypogonadism must include SHBG measurement because relying solely on total testosterone misses cases of functional hypogonadism caused by elevated SHBG 1

In Women

• Women with hirsutism or suspected androgen excess require SHBG measurement to identify those more likely to respond to estrogen therapy 2
• All patients with polycystic ovary syndrome (PCOS) should have SHBG measured, as low SHBG is a significant risk marker that contributes to increased free testosterone and worsening hyperandrogenic symptoms 1, 3
• Women with functional hypothalamic amenorrhea benefit from SHBG measurement to assess the hypothalamic-pituitary axis 1

Interpreting Low SHBG Results

Clinical Significance

• Low SHBG increases free testosterone availability, worsening symptoms of androgen excess even when total testosterone appears normal or only mildly elevated 1, 3
• A testosterone:SHBG ratio correlates well with free testosterone and helps discriminate patients with excessive androgen activity from normal individuals 2

Common Causes of Low SHBG

• Metabolic conditions: obesity, insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease 1, 3, 4
• Endocrine disorders: hypothyroidism, hyperprolactinemia, acromegaly, and Cushing's disease 1
• Medications: glucocorticoids, testosterone, anabolic steroids 1

Clinical Action for Low SHBG

• In women with hirsutism and low SHBG, consider this a marker of insulin resistance and increased cardiovascular risk; address metabolic factors aggressively 3, 4
• In PCOS patients, low SHBG indicates higher bioavailable androgens and may predict worse metabolic outcomes including progression to diabetes 3
• Calculate free androgen index (total testosterone/SHBG ratio) to assess true androgen excess 1, 2

Interpreting High SHBG Results

Clinical Significance

• High SHBG reduces free testosterone availability, causing symptoms of androgen deficiency despite normal or even elevated total testosterone levels 1
• Patients with SHBG around 74 nmol/L or higher can exhibit androgen-deficiency symptoms (reduced libido, fatigue, erectile dysfunction) while total testosterone appears reassuringly normal 1
• A free testosterone index (total testosterone/SHBG ratio) <0.3 indicates hypogonadism 1

Common Causes of High SHBG

• Endocrine disorders: hyperthyroidism, aging, hypogonadism, androgen insensitivity 1, 2
• Liver disease: hepatic cirrhosis and chronic liver disease elevate SHBG and disrupt the hypothalamic-pituitary axis 1, 2
• Medications: anticonvulsants, estrogens, thyroid hormone 1
• Other factors: smoking, HIV/AIDS 1

Clinical Action for High SHBG

• Measure free testosterone using equilibrium dialysis (gold standard) or calculate free androgen index to detect functional hypogonadism 1
• Evaluate and treat underlying causes: check thyroid function tests, liver function tests, and consider HIV testing in appropriate clinical contexts 1
• In symptomatic men with documented low free testosterone despite normal total testosterone, testosterone replacement therapy may be appropriate, with benefits including improved sexual function, well-being, muscle mass, and bone density 1

Critical Pitfalls to Avoid

• Never rely on total testosterone alone—this is the most common error and leads to missed diagnoses of both functional hypogonadism (high SHBG) and functional hyperandrogenism (low SHBG) 1
• Always consider medications and medical conditions that affect SHBG when interpreting testosterone results 1
• In women with PCOS, low SHBG may be an early biomarker of metabolic dysfunction and cardiovascular risk, not just a marker of androgen excess 3
• In men on testosterone replacement, monitor carefully with baseline and serial PSA, digital rectal exam, and hematocrit/hemoglobin checks every 3-6 months in the first year 1

Monitoring Testosterone Replacement in High SHBG Patients

• Perform baseline digital rectal exam and PSA before initiating therapy 1
• Follow PSA every 3-6 months in the first year, then annually 1
• Check hematocrit/hemoglobin regularly 1
• Monitor for urinary symptoms, sleep apnea exacerbation, and gynecomastia 1
• Consider prostate biopsy if PSA rises >1.0 ng/mL in any year 1