What is the next step in managing a woman with elevated sex hormone-binding globulin (SHBG) and normal luteinizing hormone (LH), testosterone, and estrogen levels?

Management of Elevated SHBG with Normal LH, Testosterone, and Estrogen in Women

The next step in managing a woman with elevated sex hormone-binding globulin (SHBG) and normal LH, testosterone, and estrogen levels should be to evaluate for underlying causes of elevated SHBG, including thyroid disorders, liver disease, medications, and lifestyle factors. 1

Diagnostic Approach

• Evaluate free testosterone or calculate free testosterone index (total testosterone/SHBG ratio) to assess true androgen status, as elevated SHBG can mask functional androgen deficiency despite normal total testosterone levels 1, 2
• A ratio of total testosterone/SHBG (free testosterone index) <0.3 indicates functional hypogonadism even when total testosterone appears normal 1
• Screen for common causes of elevated SHBG:
  • Thyroid function tests to rule out hyperthyroidism 1, 3
  • Liver function tests to assess for hepatic disease/cirrhosis 1, 3
  • Medication review (especially anticonvulsants, estrogens, thyroid hormone) 1, 4
  • Smoking history and HIV status assessment 1, 5

Management Strategy

• Address any identified underlying causes:

  • Treat hyperthyroidism if present 1, 3
  • Manage liver disease if identified 1
  • Consider medication adjustments if pharmaceutically induced 1
  • Recommend smoking cessation if applicable 1

• If no underlying cause is identified and the patient is symptomatic with low free testosterone index:

  • Consider referral to endocrinology for specialized evaluation 1
  • Monitor for metabolic implications as SHBG levels correlate with insulin sensitivity and cardiovascular risk 4, 5

Clinical Implications

• Elevated SHBG increases bound testosterone and reduces bioavailable testosterone, potentially causing symptoms of androgen deficiency despite normal total testosterone levels 2, 4
• SHBG measurement provides valuable information about hormone bioavailability and should be considered when interpreting sex hormone levels 4
• Abnormal SHBG levels may serve as markers for underlying metabolic or endocrine disorders 4, 5

Monitoring

• Follow-up SHBG levels after addressing underlying causes (3-6 months) 1
• Reassess symptoms and free testosterone index with treatment of underlying conditions 1
• Consider long-term monitoring of metabolic parameters as abnormal SHBG may indicate increased risk for metabolic disorders 4

Caveats and Pitfalls

• Focusing only on total hormone levels without considering SHBG can lead to misdiagnosis of hormone status 2, 4
• Normal total testosterone with elevated SHBG can mask functional androgen deficiency 2
• SHBG levels vary throughout the menstrual cycle in premenopausal women, so timing of measurement should be considered 3
• Age-related increases in SHBG are normal and should be factored into interpretation 3, 6