What is the recommended approach for estrogen replacement therapy (ERT)?

Recommended Approach for Estrogen Replacement Therapy (ERT)

Transdermal 17β-estradiol at the lowest effective dose for the shortest duration necessary is the recommended approach for estrogen replacement therapy, with progestin addition required for women with an intact uterus.1, 2, 3

Patient Selection and Initial Assessment

• Determine if patient has an intact uterus:

  • With intact uterus: Must combine estrogen with progestin to reduce endometrial cancer risk
  • Without uterus: Estrogen-only therapy is appropriate

• Evaluate for contraindications:

  • Active venous thromboembolism
  • Active liver disease
  • Uncontrolled hypertension
  • History of breast cancer
  • Current smoker (especially if >35 years)

Dosing Recommendations

Starting Dose

• Begin with lowest effective dose:
  • Transdermal estradiol: 0.025-0.0375 mg/day patch 1
  • Oral estradiol: 1-2 mg daily 2

Administration Schedule

• For women with intact uterus:

  • Cyclic regimen (3 weeks on, 1 week off) with progestin
  • Continuous combined regimen (daily estrogen and progestin)

• For women without uterus:

  • Daily estrogen-only therapy

Monitoring and Follow-up

• Reassess at 3-6 month intervals to determine if treatment is still necessary 2, 3
• Monitor for:
  • Symptom control
  • Side effects
  • Withdrawal bleeding patterns (if on cyclic therapy)
  • Abnormal vaginal bleeding requires diagnostic evaluation

Special Considerations

Premature Ovarian Insufficiency (POI)

• Higher doses may be needed initially
• Note that women with POI may still be fertile (5-10% conception rate) 1
• ERT does not provide contraception

Cancer Survivors

• For endometrial cancer survivors, ERT remains controversial but may be reasonable for low-risk recurrence patients 4
• Strict follow-up is essential, especially for TBI or Hodgkin lymphoma survivors who have increased breast cancer risk 4
• Annual imaging from age 25 years recommended for high-risk patients 4

Route of Administration

• Transdermal route preferred over oral due to:
  • Lower venous thromboembolism risk
  • Lower stroke risk
  • Avoidance of first-pass liver metabolism

Duration of Therapy

• Use for shortest duration consistent with treatment goals and risks
• Attempt to discontinue or taper medication at 3-6 month intervals 2, 3
• For osteoporosis prevention, longer duration may be necessary

Common Pitfalls to Avoid

1. Failing to add progestin for women with intact uterus
2. Using ERT as contraception (it does not prevent pregnancy)
3. Not monitoring for abnormal bleeding, which requires evaluation
4. Continuing therapy without periodic reassessment
5. Using standard doses in all patients rather than individualizing based on symptoms

The evidence strongly supports that ERT should be prescribed at the lowest effective dose for the shortest duration necessary to control symptoms, with careful consideration of individual risk factors and regular reassessment of the need for continued therapy.