What is the recommended dosage and regimen for progesterone and estrogen therapy?

Recommended Dosage and Regimen for Progesterone and Estrogen Therapy

For postmenopausal women requiring hormone therapy, the recommended first-line approach is transdermal estradiol 50-100 μg/day with oral micronized progesterone 200 mg daily for 12-14 days per month in women with an intact uterus. 1

Estrogen Therapy Options

Transdermal Estrogen (First Choice)

• Starting dose: 50 μg/24 hours of estradiol via patch 1
• Maintenance dose: 50-100 μg/24 hours, adjusted based on symptom control 1
• Administration schedule: Patches changed either twice weekly or weekly depending on specific product 1
• Benefits: Avoids first-pass liver metabolism, lower risk of venous thromboembolism, more stable hormone levels 1

Oral Estrogen (Second Choice)

• Starting dose: 1 mg daily of estradiol 2
• Maintenance dose: 1-2 mg daily, adjusted as necessary to control symptoms 2
• Maximum dose: 2-4 mg daily of oral estradiol 1

Progesterone Options for Women with Intact Uterus

First Choice: Micronized Progesterone

• Sequential regimen: 200 mg daily for 12-14 days per month 3
• Benefits: Associated with lower risk of cardiovascular disease and venous thromboembolism compared to synthetic progestins 3, 4

Alternative Options:

• Medroxyprogesterone acetate (MPA): 10 mg daily for 12-14 days per month (sequential) or 2.5 mg daily (continuous) 3
• Dydrogesterone: 10 mg daily for 12-14 days per month (sequential) or 5 mg daily (continuous) 3

Administration Regimens

Sequential Combined Regimen

• Estrogen administered continuously
• Progestogen administered cyclically for 12-14 days every 28 days
• Results in withdrawal bleeding 3

Continuous Combined Regimen

• Both estrogen and progestogen administered continuously
• Avoids withdrawal bleeding
• Recommended for women who prefer to avoid monthly bleeding 3

Important Considerations

1. Endometrial Protection:

   • Women with an intact uterus must receive progestin with estrogen to prevent endometrial cancer 2, 5
   • Continuous progestin use is associated with reduced risk of endometrial cancer (OR = 0.2) compared to cyclic use (OR = 2.9) 5

2. Breast Cancer Risk:

   • Combined estrogen-progestin therapy is associated with a small increased risk of breast cancer (HR = 1.26) 6
   • Natural progesterone may have a lower breast cancer risk compared to synthetic progestins 4

3. Cardiovascular Risk:

   • The Women's Health Initiative found increased risk of coronary heart disease (HR = 1.29), stroke (HR = 1.41), and pulmonary embolism (HR = 2.13) with combined estrogen-progestin therapy 6
   • Transdermal estrogen has lower thrombotic risk than oral formulations 1

4. Duration of Therapy:

   • Use the lowest effective dose for the shortest duration consistent with treatment goals 2
   • Reevaluate necessity of treatment every 3-6 months 2

5. Ovarian Cancer Risk:

   • Estrogen-alone therapy increases ovarian cancer risk (RR = 1.22 per 5 years of use)
   • Adding progestin reduces this risk (RR = 1.10 per 5 years of use) 7

Specific Clinical Scenarios

For Premature Ovarian Insufficiency (POI)

• Transdermal estradiol 50-100 μg/24 hours 3
• Add progestin after at least 2 years of estrogen therapy in adolescents or when breakthrough bleeding occurs 1

For Endometrial Cancer Prevention

• In women with intact uterus, continuous progestin regimen provides better endometrial protection than cyclic regimen 5
• Progestins (e.g., MPA 200 mg or MA 160 mg) are recommended for hormone receptor-positive endometrial tumors 3

Monitoring

• Clinical review should occur every 3-6 months initially, then annually 1, 2
• Assess symptom control, side effects, and compliance
• For women with history of breast cancer, consider annual breast imaging from age 25 onward 3

Remember that this regimen applies to hormone therapy for menopausal symptoms or prevention of chronic conditions. The specific dosage and regimen should be adjusted based on the indication, patient's response, and risk factors.