What do traditional blood tests measure in terms of hormone levels?

Traditional Blood Tests and Hormone Measurement

Traditional Blood Tests Measure Bound Total Hormones

Traditional blood tests primarily measure bound total hormones (option B), not free hormone levels, which are the biologically active fraction in the bloodstream. 1 This is critical to understand when interpreting hormone test results for clinical decision-making.

Characteristics of Traditional Blood Tests

• Blood tests typically measure the total concentration of hormones, which includes both:

  • Protein-bound hormone (bound to SHBG or albumin)
  • Free (unbound) hormone

• The Endocrine Society recommends morning serum total testosterone measurement as the first-line approach for assessing androgen status in men 1

• For many hormones, the bound fraction represents 95-99% of the total hormone concentration, while only the free fraction (1-5%) is biologically active 2

Limitations of Traditional Blood Tests

• Total hormone levels may not accurately reflect the biologically active hormone available to tissues, particularly in conditions that affect binding proteins 1

• SHBG can be affected by various factors including:

  • Age
  • Obesity
  • Diabetes
  • Liver disease
  • Medications 1

Measurement of Free Hormone Levels

Free hormone levels (option C) are not typically measured by traditional blood tests but require specialized techniques:

1. Reference Methods (gold standard):

   • Equilibrium dialysis
   • Ultrafiltration 3, 2

2. Calculated Methods:

   • Free testosterone calculated from total testosterone and SHBG measurements
   • These calculations use validated equations 1, 3

3. Invalid Methods (should be avoided):

   • Direct "analog" free testosterone immunoassays are unreliable 1
   • Free androgen index (FAI) is mathematically invalid for men 1

Serum Testing Capabilities

All of the following can be measured with serum testing:

• Free and Total testosterone
• Sex hormone binding globulin (SHBG)
• FSH
• 2-hydroxy estrone

Saliva Testing Applications

Saliva testing is particularly good for measuring free estradiol (option A) because:

• Saliva is an ultrafiltrate of blood
• Only free (unbound) hormones diffuse into saliva
• It provides a non-invasive assessment of the biologically active hormone fraction 4

Saliva testing is not ideal for measuring TSH, total testosterone, or LH, as these are either protein-bound or not readily diffused into saliva.

First Test for Surgical Menopause

For a patient with surgical menopause, serum testing (option B) is the best first test to quantify estrogen production. This provides the most standardized and reliable initial assessment of hormone status.

Advantages of serum testing in this scenario:

• Widely available and standardized methodology
• Provides baseline total estradiol levels
• Can simultaneously measure other relevant hormones (FSH, LH)
• Results are more easily interpreted against established reference ranges

While dried urine testing can provide information about estrogen metabolites, and salivary testing measures free estradiol, serum testing remains the standard first-line approach for initial hormone assessment in surgical menopause.

Estrogen Detoxification Enzymes

All of the following enzymes are involved in estrogen detoxification except CYP 19 (option D):

• CYP 1A1 - hydroxylates estrogens
• COMT - methylates catechol estrogens
• CYP 3A4 - hydroxylates estrogens

CYP 19 (aromatase) is involved in estrogen synthesis, not detoxification, as it converts androgens to estrogens.