What is the recommended hormone replacement therapy (HRT) regimen using estrogen cream and progesterone (progestin)?

Recommended HRT Regimen with Estrogen Cream and Progesterone

For women with an intact uterus requiring hormone replacement therapy, the recommended regimen is transdermal estradiol (estrogen cream) combined with oral progesterone 200 mg daily at bedtime for 12 continuous days per 28-day cycle. 1

Estrogen Component

Recommended Formulation and Dosage

• Transdermal estradiol is preferred over oral formulations due to:
  • Avoidance of first-pass hepatic metabolism
  • More physiological estradiol:estrone ratio
  • Lower cardiovascular risk profile (reduced risk of venous thromboembolism and stroke) 1
• Starting dose should be the lowest effective dose:
  • Begin with low-dose transdermal estradiol (0.025-0.05 mg/day patch or equivalent cream)
  • Titrate based on symptom control after 3-6 months 1, 2

Administration

• Apply estrogen cream to clean, dry skin in the upper, outer thigh or buttock area
• Rotate application sites to prevent skin irritation
• Apply at the same time each day for consistent hormone levels 2

Progesterone Component

Necessity and Rationale

• Progesterone is essential for women with an intact uterus taking estrogen therapy to prevent endometrial hyperplasia and cancer 1, 3
• Without progesterone, estrogen alone significantly increases risk of endometrial hyperplasia (64% vs 6% with combined therapy) 3

Recommended Formulation and Dosage

• Natural (micronized) progesterone has a better safety profile than synthetic progestins 1
• Dosage: 200 mg oral progesterone daily at bedtime for 12 continuous days per 28-day cycle 1, 3
• Take at bedtime to minimize side effects of drowsiness and dizziness 1

Administration Schedule Options

1. Cyclic regimen (preferred for newly menopausal women):

   • Estrogen cream daily
   • Progesterone 200 mg daily for 12-14 days per month 1, 3
   • Expect withdrawal bleeding during progesterone-free days

2. Continuous regimen (for women >1 year post-menopause):

   • Estrogen cream daily
   • Progesterone 100 mg daily continuously 1
   • Minimizes breakthrough bleeding after initial adjustment period

Monitoring and Follow-up

• Initial evaluation at 3-6 months after starting therapy 1
• Annual clinical review thereafter, focusing on:
  • Symptom control and compliance
  • Blood pressure and weight
  • Any abnormal vaginal bleeding (requires prompt evaluation) 1
• No routine laboratory monitoring required unless prompted by specific symptoms 4

Important Considerations and Precautions

Contraindications

• History of breast cancer
• Active thromboembolic disorders
• History of arterial thrombotic disease
• Undiagnosed vaginal bleeding
• Liver problems 1, 2

Special Populations

• Women with hypertension: Transdermal estradiol is strongly preferred 4, 1
• Women with endometriosis who required oophorectomy: Combined estrogen/progesterone therapy is effective 4
• Women with BRCA1/2 mutations without personal history of breast cancer: HRT is a treatment option after prophylactic bilateral salpingo-oophorectomy 4

Common Side Effects to Monitor

• Breast tenderness
• Headache
• Nausea
• Abdominal bloating
• Mood changes 3

Pitfalls to Avoid

1. Using estrogen alone in women with intact uterus - This significantly increases endometrial cancer risk 3

2. Starting with high doses - Begin with lowest effective dose to minimize side effects and risks 1, 5

3. Improper progesterone timing - Inadequate duration of progesterone therapy may not provide sufficient endometrial protection 1

4. Ignoring breakthrough bleeding - Persistent or recurrent abnormal vaginal bleeding requires prompt evaluation to rule out endometrial pathology 1, 3

5. Continuing therapy without periodic reassessment - Regular evaluation is necessary to determine if treatment is still needed and appropriate 2

By following this regimen and monitoring protocol, you can provide effective symptom relief while minimizing risks associated with hormone replacement therapy.