Is an estradiol (E2) to testosterone (T) ratio greater than 5% indicative of estrogen excess?

Estradiol/Testosterone Ratio and Estrogen Excess

An estradiol/testosterone ratio greater than 5% is not established as a definitive marker of estrogen excess in current medical guidelines. There is insufficient evidence in the medical literature to support using this specific ratio as a diagnostic threshold for estrogen excess.

Current Understanding of Hormone Ratios

The relationship between estradiol and testosterone is complex and varies based on several factors:

• The testosterone:estradiol ratio has been studied more extensively than the estradiol:testosterone ratio, with some research suggesting a beneficial range between 10 and 30 (calculated as testosterone in ng/dL divided by estradiol in pg/mL) 1
• Higher testosterone:estradiol ratios appear associated with improved spermatogenesis but reduced bone density 1
• Lower testosterone:estradiol ratios have been associated with thyroid dysfunction 1

Clinical Significance of Hormone Ratios

In postmenopausal women, research has shown:

• A higher testosterone/estradiol ratio was associated with elevated risk for cardiovascular disease, coronary heart disease, and heart failure 2
• Higher testosterone levels were associated with increased cardiovascular and coronary heart disease risk 2
• Higher estradiol levels were associated with lower coronary heart disease risk 2

However, these findings relate to the testosterone/estradiol ratio (inverse of what was asked) and don't establish a specific 5% threshold for the estradiol/testosterone ratio.

Diagnostic Approach for Hormone Imbalance

When evaluating potential hormone imbalances, guidelines recommend:

1. Comprehensive hormone panel:

   • Total and free testosterone
   • Estradiol
   • Sex hormone-binding globulin (SHBG)
   • FSH and LH
   • Thyroid function tests 3

2. Consider confounding factors:

   • Body mass index (obesity or malnutrition)
   • Liver disease/cirrhosis
   • Polycystic ovary syndrome (PCOS)
   • Medications (especially hormone therapies) 3

3. Use appropriate testing methods:

   • The Endocrine Society recommends using calculated free testosterone (cFT) rather than free androgen index (FAI) 3
   • Liquid chromatography tandem mass spectrometry provides more accurate hormone measurements than immunoassays 4

Special Considerations

For Transgender Individuals

In transgender women/transfeminine individuals on gender-affirming hormone therapy:

• The goal is to bring testosterone levels to <50 ng/dL (female range) 5
• Estrogen therapy can alter body composition, decreasing lean body mass and increasing body fat 5
• Monitoring of both estradiol and testosterone levels is important, but specific ratio targets are not established in guidelines 5

For Patients with Adrenal Disorders

In cases of suspected adrenocortical carcinoma (ACC) or virilization:

• Serum testing for excess androgens should be performed 5
• Testing may include DHEAS, testosterone, 17b-estradiol, and other hormones 5
• However, specific estradiol/testosterone ratio thresholds are not mentioned in guidelines 5

Conclusion

While hormone ratios may provide valuable clinical information, the specific estradiol/testosterone ratio of 5% is not established in current medical guidelines as a diagnostic threshold for estrogen excess. Clinicians should rely on comprehensive hormone testing, clinical presentation, and established diagnostic criteria for conditions associated with hormone imbalances rather than a single ratio threshold.