What is the recommended course of action for a 48-year-old female with elevated testosterone levels and abnormal sex hormone-binding globulin (SHBG) levels?

Evaluation and Management of Elevated Testosterone in a 48-Year-Old Female

A 48-year-old female with elevated testosterone levels (19 ng/dL) and free testosterone (2.6 ng/dL) with SHBG of 45 nmol/L requires further evaluation to determine the cause of hyperandrogenism and appropriate management.

Initial Assessment

• Elevated testosterone in females requires thorough investigation as it may indicate underlying pathology that could impact morbidity and mortality 1
• When total testosterone is elevated with normal SHBG (as in this case), the free testosterone calculation is particularly important for determining the biologically active androgen levels 2
• The patient's values show both elevated total and free testosterone, indicating true hyperandrogenism rather than just SHBG abnormalities 1

Diagnostic Algorithm

Step 1: Confirm the Elevation

• Repeat morning testosterone measurements to confirm the elevation, as single measurements can be misleading 3
• Ensure testing is performed with reliable assays - radioimmunological assay following extraction or mass spectrometry is recommended 1

Step 2: Additional Laboratory Testing

• Measure DHEAS levels to evaluate for possible adrenal sources of androgens 1
  • DHEAS >600 mg/dL suggests androgen-secreting adrenal adenoma
  • Normal DHEAS with elevated testosterone suggests ovarian source (hyperthecosis or ovarian tumor)
• Consider checking other androgens including androstenedione 2
• Evaluate for insulin resistance and metabolic syndrome, which are commonly associated with hyperandrogenism 4

Step 3: Imaging Studies

• If testosterone is more than twice the upper limit of normal or if clinical suspicion is high:
  • Adrenal imaging (CT or MRI) if DHEAS is elevated
  • Ovarian ultrasound or MRI to evaluate for ovarian pathology if DHEAS is normal 1

Management Considerations

• Management should be directed at the underlying cause rather than just treating the laboratory abnormality 1

• For metabolic causes (insulin resistance, PCOS):

  • Lifestyle modifications including weight loss and increased physical activity can help reduce testosterone levels 4
  • Consider metformin if insulin resistance is present 4

• For tumors (adrenal or ovarian):

  • Surgical intervention is typically required 1

• For idiopathic hyperandrogenism:

  • Anti-androgen therapy may be considered if symptoms are bothersome (hirsutism, acne) 1

Clinical Implications and Monitoring

• Elevated testosterone in females is associated with:

  • Increased cardiovascular risk factors 4
  • Metabolic abnormalities including insulin resistance 4
  • Potential impact on bone mineral density 3

• Regular monitoring should include:

  • Repeat testosterone and free testosterone measurements to assess response to treatment 3
  • Evaluation of clinical symptoms (hirsutism, acne, menstrual irregularities) 1
  • Screening for metabolic complications (lipids, glucose tolerance) 4

Common Pitfalls to Avoid

• Failing to confirm elevated testosterone with repeat testing 3
• Overlooking the importance of free testosterone calculations in women with normal SHBG 2
• Not considering rare but serious causes such as androgen-secreting tumors 1
• Treating laboratory values without correlating with clinical symptoms 3
• Ignoring the relationship between hyperandrogenism and metabolic disorders 4