What does an elevated sex‑hormone‑binding globulin (SHBG) level of 84 nmol/L indicate in an adult male?

Elevated SHBG in Adult Males: Clinical Significance and Interpretation

An SHBG level of 84 nmol/L in an adult male is elevated and indicates that a larger proportion of circulating testosterone is tightly bound and biologically unavailable, which may result in functional hypogonadism even when total testosterone appears normal.

Understanding SHBG Physiology

• SHBG is a liver-synthesized glycoprotein that binds testosterone and estradiol with high affinity, rendering the bound fraction biologically inactive 1
• Only free (unbound) and albumin-bound testosterone are biologically available to target tissues 1
• SHBG levels vary remarkably widely in clinical populations—ranging from 6 to 109 nmol/L in men presenting to men's health centers, representing an 18-fold difference 2
• The mean SHBG in younger men (≤54 years) is approximately 27.7 nmol/L, while in older men (≥55 years) it rises to 36.6 nmol/L 2
• Your level of 84 nmol/L places you well above the 95th percentile for both age groups, with only 2.2% of younger men and 9% of older men having SHBG >60 nmol/L 2

Common Causes of Elevated SHBG

Endocrine Disorders

• Hyperthyroidism is a major cause of elevated SHBG; thyroid hormones directly stimulate hepatic SHBG production 1, 3
• Hypogonadism (low testosterone states) paradoxically elevate SHBG through loss of androgen suppression 1
• Androgen insensitivity syndromes result in markedly elevated SHBG 1

Hepatic Disease

• Chronic liver disease and hepatic cirrhosis elevate SHBG, though the mechanism remains incompletely understood 1, 3
• In advanced cirrhosis, SHBG may eventually decline as synthetic liver function deteriorates 4
• Elevated estrogen from portosystemic shunting in liver disease suppresses the hypothalamic-pituitary axis, contributing to hypogonadism, testicular atrophy, and feminization—SHBG elevation is a consequence, not the cause 4

Medications

• Anticonvulsants (phenytoin, carbamazepine) induce hepatic SHBG synthesis 1, 3, 4
• Exogenous estrogens markedly increase SHBG 1, 3, 4
• Thyroid hormone replacement raises SHBG levels 1, 3, 4

Other Factors

• Aging progressively increases SHBG, with mean levels rising from 27.7 nmol/L in men ≤54 years to 36.6 nmol/L in men ≥55 years 2, 4
• HIV/AIDS is associated with elevated SHBG 1, 4
• Smoking can increase SHBG concentrations 4

Clinical Implications: Functional Hypogonadism

The Free Testosterone Paradox

• Elevated SHBG binds a larger fraction of circulating testosterone, reducing free (bioavailable) testosterone even when total testosterone is in the normal or borderline-normal range 1, 5
• This creates "functional hypogonadism"—symptomatic androgen deficiency despite seemingly adequate total testosterone 5
• Critically, in vivo studies show that elevated SHBG does not necessarily lower non-SHBG-bound testosterone in men with an intact hypothalamic-pituitary-gonadal axis, because the body compensates by increasing total testosterone production 6
• However, when compensatory mechanisms fail (e.g., in aging, chronic illness, or borderline testicular function), elevated SHBG can unmask true androgen deficiency 5

Diagnostic Approach

Step 1: Confirm Testosterone Status

• Obtain two separate fasting morning total testosterone measurements (8–10 AM) to establish whether biochemical hypogonadism is present (both values <300 ng/dL) 5
• A single measurement is insufficient due to diurnal variation and assay variability 5

Step 2: Assess Free Testosterone

• In men with total testosterone in the "gray zone" (231–346 ng/dL) or with elevated SHBG, measure free testosterone by equilibrium dialysis (gold standard) or calculate the free androgen index (FAI = total testosterone ÷ SHBG × 100) 5, 7
• An FAI <30 indicates true hypogonadism even when total testosterone is borderline-normal 5
• Direct immunoassays for free testosterone are unreliable in the setting of abnormal SHBG and should be avoided 5

Step 3: Differentiate Primary vs. Secondary Hypogonadism

• After confirming low testosterone, measure serum LH and FSH to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism 5
• Low or inappropriately normal LH/FSH with low testosterone indicates secondary hypogonadism 5
• Elevated LH/FSH with low testosterone indicates primary testicular failure 5

Step 4: Identify Reversible Causes of Elevated SHBG

• Measure TSH to exclude hyperthyroidism 5
• Obtain liver function tests and hepatitis serologies if hepatic disease is suspected 5
• Review medications for SHBG-elevating drugs (anticonvulsants, estrogens, thyroid hormone) 5
• Consider HIV testing in at-risk populations 5

Treatment Considerations

When Testosterone Therapy May Be Indicated

• Testosterone replacement is justified only when both biochemical hypogonadism (two morning testosterone <300 ng/dL) and specific symptoms (diminished libido or erectile dysfunction) are present 5
• In men with elevated SHBG and borderline total testosterone, treatment decisions should be guided by free testosterone or FAI, not total testosterone alone 5
• Expected benefits are modest: small but significant improvements in sexual function (standardized mean difference ≈0.35), with little to no effect on energy, mood, physical function, or cognition 5

Addressing Underlying Causes First

• Treat hyperthyroidism before considering testosterone therapy, as SHBG will normalize with euthyroid status 5
• Optimize liver function in hepatic disease; in cirrhosis, use the free testosterone index (total testosterone ÷ SHBG <0.3) to define hypogonadism 5
• Discontinue or substitute SHBG-elevating medications when feasible 5
• In obesity-related secondary hypogonadism, attempt weight loss through hypocaloric diet (500–750 kcal/day deficit) and structured exercise (≥150 min/week moderate-intensity aerobic activity plus resistance training 2–3 times/week) before initiating testosterone 5

Monitoring During Testosterone Therapy

• Testosterone therapy itself lowers SHBG through androgen suppression of hepatic synthesis 8
• In hypogonadal men treated with testosterone enanthate, SHBG fell from 16.4 ng/mL to 4.3 ng/mL after 3 months 8
• This SHBG reduction amplifies the increase in free testosterone, potentially improving clinical response 8

Critical Pitfalls to Avoid

• Do not diagnose hypogonadism based on total testosterone alone when SHBG is elevated; always assess free testosterone or calculate FAI 5
• Do not attribute symptoms solely to elevated SHBG without measuring actual testosterone levels and excluding other causes (thyroid disease, liver disease, medications) 4
• Do not initiate testosterone therapy without first addressing reversible causes of elevated SHBG (hyperthyroidism, hepatic disease, medication adjustment) 5
• Do not rely on direct immunoassays for free testosterone in men with abnormal SHBG; use equilibrium dialysis or validated calculated formulas 5
• Recognize that SHBG is often a marker of underlying disease (liver disease, thyroid dysfunction) rather than the primary pathology 4, 3

Summary Algorithm

1. Measure two fasting morning total testosterone levels (8–10 AM) 5
2. If total testosterone is <300 ng/dL or in the gray zone (231–346 ng/dL), calculate FAI or measure free testosterone by equilibrium dialysis 5
3. If FAI <30 or free testosterone is low, measure LH and FSH to classify hypogonadism 5
4. Screen for reversible causes: TSH, liver function tests, medication review, HIV testing (if indicated) 5
5. Treat underlying conditions (hyperthyroidism, hepatic disease, medication adjustment) before considering testosterone therapy 5
6. If biochemical hypogonadism persists and sexual symptoms are present, initiate testosterone replacement with transdermal gel as first-line (lower erythrocytosis risk) 5
7. Monitor testosterone, hematocrit, and PSA at 2–3 months, then every 3–6 months during the first year, then annually 5