Is high Sex Hormone-Binding Globulin (SHBG) with high total testosterone and normal free testosterone a concern if I'm experiencing hypogonadic symptoms?

High SHBG with High Total Testosterone and Hypogonadal Symptoms

High SHBG with high total testosterone but normal free testosterone can indeed cause hypogonadal symptoms, as free testosterone is the biologically active form that matters clinically, and further evaluation is warranted to determine the underlying cause and appropriate treatment. 1, 2

Understanding Your Hormone Profile

When evaluating testosterone status, it's important to understand the relationship between different measurements:

• Total testosterone: Measures all testosterone in blood (both bound and unbound)
• Free testosterone: The biologically active portion (1-2% of total) that is unbound and available to tissues
• SHBG: A protein that binds testosterone, making it unavailable to tissues

Why You Can Have Symptoms Despite Normal Free Testosterone

Your situation represents a classic hormonal paradox:

• High total testosterone suggests adequate hormone production
• High SHBG means more testosterone is bound and unavailable
• Normal free testosterone might still be inadequate for your body's needs

Diagnostic Approach

1. Confirm your hormone profile:

   • Measure morning total testosterone on at least 2 separate days 3
   • Verify free testosterone levels using reliable methods (equilibrium dialysis or calculated free testosterone)
   • Check luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to determine if there's a central vs. peripheral issue 1

2. Rule out conditions that increase SHBG:

   • Age (SHBG increases with age) 4
   • Liver disease
   • Hyperthyroidism
   • HIV infection
   • Medications (estrogens, anticonvulsants)

3. Evaluate for other causes of hypogonadal symptoms:

   • Cardiovascular disease
   • Diabetes
   • Hypertension
   • Sleep apnea
   • Psychological factors (anxiety, depression, stress) 1

Treatment Considerations

If your evaluation confirms functional hypogonadism despite normal laboratory values:

1. Lifestyle modifications (first-line approach):

   • Weight management (if overweight)
   • Regular exercise (150 minutes weekly of moderate-intensity exercise)
   • Mediterranean diet
   • Limit alcohol consumption 1

2. Consider testosterone therapy if symptoms persist and other causes are ruled out:

   • Target mid-normal values for free testosterone
   • Options include intramuscular injections, transdermal patches or gels
   • Avoid oral alkylated testosterone due to hepatotoxicity risk 1

3. Monitor treatment effectiveness:

   • Reassess symptoms using validated questionnaires
   • Follow-up within 1-3 months of initiating therapy 1
   • Monitor testosterone levels, PSA, and hematocrit

Important Considerations

• Age factor: Studies show that men over 60 years have a 26.3% frequency of normal total testosterone but low free testosterone due to elevated SHBG 2
• SHBG threshold: Research indicates an SHBG level above 44.40 nmol/L may predict symptomatic late-onset hypogonadism 4
• Albumin levels: Low albumin can further decrease testosterone binding capacity and worsen symptoms 5

Cautions and Contraindications

If testosterone therapy is considered, it should not be used in men with:

• Breast or prostate cancer
• Desire for current or future fertility
• Hematocrit >50%
• Severe untreated sleep apnea
• Severe lower urinary tract symptoms
• Uncontrolled heart failure 1

When to Seek Specialist Care

Consider referral to an endocrinologist or urologist if:

• Symptoms persist despite initial management
• There are complex hormonal abnormalities
• You have contraindications to standard treatments 1