Is high Sex Hormone-Binding Globulin (SHBG) with high testosterone a clinical concern?

High SHBG with High Testosterone: Clinical Implications

High SHBG with high testosterone is typically not a clinical concern as long as free testosterone levels remain normal, since the elevated SHBG may be compensating to maintain appropriate levels of bioavailable testosterone. 1

Understanding SHBG and Testosterone Relationship

Sex Hormone-Binding Globulin (SHBG) is a glycoprotein that binds to testosterone with high affinity, affecting its bioavailability. When evaluating testosterone status, it's critical to consider:

• SHBG binds approximately 44-65% of circulating testosterone, rendering it biologically unavailable
• Free testosterone (only 2-3% of total) is the biologically active form
• The relationship between total testosterone, SHBG, and free testosterone determines clinical effects

Clinical Assessment for High SHBG with High Testosterone

1. Measure Free Testosterone

• Calculate free testosterone using the Vermeulen equation or measure directly
• Free testosterone index (ratio of total testosterone/SHBG) is a better indicator of gonadal status than total testosterone alone 1
• A normal free testosterone level suggests adequate bioavailable hormone despite high SHBG

2. Evaluate for Symptoms

Common symptoms to assess include:

• Sexual symptoms: reduced libido, erectile dysfunction, decreased morning erections 2
• Physical symptoms: decreased energy, physical strength, activity levels 2
• Psychological symptoms: low mood, decreased motivation, fatigue 2

3. Investigate Causes of Elevated SHBG

Common causes include 2, 1:

• Medications: anticonvulsants, estrogens, thyroid hormone
• Hyperthyroidism
• Hepatic disease
• Advanced age
• Smoking
• HIV/AIDS

Management Approach

If Asymptomatic with Normal Free Testosterone:

• No specific treatment needed
• Routine monitoring with follow-up testing in 3-6 months 1
• Focus on addressing any underlying conditions causing elevated SHBG

If Symptomatic or Low Free Testosterone:

1. Treat underlying causes of elevated SHBG if identified:

   • Manage hyperthyroidism
   • Address liver disease
   • Review and modify medications if possible

2. Consider testosterone status monitoring:

   • Morning measurements are preferred due to diurnal variation 1
   • Track symptoms alongside laboratory values

Important Considerations

• Relying solely on total testosterone without considering SHBG can lead to incorrect clinical conclusions 1
• There is remarkable interindividual variability in SHBG concentrations, with nearly 20-fold differences observed in clinical populations 3
• Higher SHBG, independently of total testosterone, has been associated with subjective and objective androgen deficiency features 4
• Treating elevated total testosterone when free testosterone is normal may lead to adverse effects without clinical benefit 1

Pitfalls to Avoid

• Don't focus exclusively on laboratory values; clinical symptoms are equally important
• Don't overlook potential underlying causes of elevated SHBG
• Avoid treating based on total testosterone levels alone without considering SHBG and free testosterone
• Remember that SHBG levels increase naturally with age, with mean values of 27.7±13.3 nmol/L in men ≤54 years and 36.6±15.8 nmol/L in men ≥55 years 3

If you're experiencing symptoms despite high testosterone and high SHBG, further evaluation of your free testosterone levels and investigation of potential underlying causes is warranted.