Should estradiol (E2) levels be checked to guide hormone replacement therapy (HRT)?

From the Research

Routine estradiol (E2) level monitoring is generally not recommended to guide hormone replacement therapy (HRT) for most patients. Clinical assessment of symptom relief and side effects is typically more valuable than laboratory values in determining appropriate HRT dosing. For standard oral estrogen therapy, target E2 levels are not well established, and levels can fluctuate significantly throughout the day, especially with oral formulations. However, E2 monitoring may be appropriate in specific situations: when using transdermal or injectable estrogen in transgender care (aiming for levels in the premenopausal female range of 100-200 pg/mL), when symptoms persist despite seemingly adequate therapy, when verifying absorption issues, or when using very high doses.

Key Considerations

• The clinical response to therapy remains the most important metric for most patients, as symptom relief correlates poorly with specific estradiol levels in many individuals 1.
• When testing is performed, blood should be drawn at the appropriate time—at trough levels before the next dose for transdermal or injectable forms, or 4-6 hours after taking oral estrogen.
• HRT is considered the gold standard for management of vasomotor and vaginal symptoms of menopause, but it carries significant risks, including risk of stroke, cardiovascular disease, breast cancer, and venous thromboembolism 2.

Specific Situations for E2 Monitoring

• Transdermal or injectable estrogen in transgender care
• Persistent symptoms despite adequate therapy
• Verifying absorption issues
• Using very high doses

Clinical Assessment

• Symptom relief and side effects are more valuable than laboratory values in determining appropriate HRT dosing 3.
• Clinical characteristics of the participants, especially age, time since menopause, and comorbidity status, should be considered when prescribing HRT 4.