Management of Elevated SHBG with Normal Total and Free Testosterone
No treatment is indicated for isolated elevated SHBG when both total testosterone (593 ng/dL) and free testosterone (84.5 pg/mL) are within normal ranges, as these values indicate eugonadal status. 1
Key Interpretation of Laboratory Values
Your hormone profile demonstrates:
- Total testosterone of 593 ng/dL is normal (typical reference range 300-1000 ng/dL) 1
- Free testosterone of 84.5 pg/mL is normal (typically >63-70 pg/mL indicates eugonadal status) 2, 3
- Elevated SHBG at 61 nmol/L requires investigation of underlying causes but does not necessitate testosterone therapy 1, 4
The free testosterone level is the critical determinant of androgen status, not SHBG alone. 2, 3 Recent evidence demonstrates that low free testosterone, even with normal total testosterone, correlates with hypogonadal symptoms, whereas normal free testosterone despite elevated SHBG is not associated with androgen deficiency symptoms 3.
Clinical Assessment Algorithm
Step 1: Symptom Evaluation
Assess for specific hypogonadal symptoms, which are absent in your case given normal free testosterone: 1
- Sexual symptoms: reduced libido, erectile dysfunction, decreased spontaneous erections
- Physical symptoms: decreased vigorous activity, reduced energy, hot flushes
- Psychological symptoms: low mood, decreased motivation, fatigue
Men with normal free testosterone (>220 pmol/liter or ~63 pg/mL) lack features of androgen deficiency regardless of SHBG elevation. 3
Step 2: Identify Causes of Elevated SHBG
Investigate conditions that increase SHBG production: 1, 4
- Liver disease: Chronic liver disease and cirrhosis commonly elevate SHBG 1
- Hyperthyroidism: Thyroid hormones stimulate SHBG synthesis 4
- Medications: Estrogens, anticonvulsants increase SHBG 4
- Aging: Natural age-related increase 1
- Low body weight/malnutrition: Inversely related to BMI 5
Step 3: Targeted Laboratory Workup
Order additional tests based on clinical suspicion: 1
- Thyroid function tests (TSH, free T4) to exclude hyperthyroidism 1
- Liver function tests (AST, ALT, bilirubin, albumin) if liver disease suspected 1
- LH and FSH to assess hypothalamic-pituitary-gonadal axis function 1
- Morning repeat testosterone and SHBG to confirm values (due to diurnal variation) 1
Management Recommendations
Primary Management: Observation Only
No testosterone therapy should be initiated in eugonadal men with normal free testosterone. 1 The 2025 European Association of Urology guidelines explicitly state: "Do not use testosterone therapy in eugonadal men" (Strong recommendation) 1.
Address Underlying Causes
- If hyperthyroid: Treat thyroid disorder, which will normalize SHBG 4
- If liver disease: Manage underlying hepatic condition; SHBG may remain elevated but does not require specific treatment if free testosterone is normal 1
- If medication-induced: Consider alternative medications if clinically appropriate 4
Monitoring Strategy
Repeat assessment only if symptoms develop: 1, 2
- Recheck total testosterone, free testosterone, and SHBG if sexual, physical, or psychological symptoms emerge
- Annual monitoring is unnecessary in asymptomatic men with normal free testosterone 1
Critical Clinical Pitfalls to Avoid
Do not treat based on SHBG elevation alone. 2, 3 The most common error is initiating testosterone therapy based on elevated SHBG without confirming low free testosterone. Studies demonstrate that 75.3% of men with borderline total testosterone have normal free testosterone and lack hypogonadal symptoms 2.
Do not use total testosterone alone for diagnosis when SHBG is abnormal. 1, 2 In conditions with elevated SHBG (liver disease, hyperthyroidism, aging), the free testosterone index (total testosterone/SHBG ratio) or calculated free testosterone provides more accurate assessment of androgen status 1.
Testosterone therapy in eugonadal men carries risks without benefits: 1
- Polycythemia (hematocrit >54% requires intervention) 1
- Suppression of spermatogenesis and fertility 1
- No improvement in cognition, vitality, or physical strength in eugonadal aging men 1
Special Considerations
If liver disease is present: The elevated SHBG reflects hepatic dysfunction, and SHBG synthesis is stimulated by estrogens in the context of portosystemic shunting 1. However, treatment focuses on the underlying liver disease, not the SHBG elevation itself 1.
The free testosterone index calculation (total testosterone/SHBG ratio <0.3 indicates hypogonadism) can be used as an alternative assessment method, particularly in alcoholic liver disease where SHBG is frequently elevated 1.