What is the recommended dose of progesterone (P4) for hormone replacement therapy (HRT) in a typical adult female patient?

Recommended Progesterone Dosage for Hormone Replacement Therapy

For adult females requiring hormone replacement therapy (HRT), the recommended dose of progesterone is 200 mg daily for 12-14 days per 28-day cycle when using oral micronized progesterone. 1

Progesterone Administration in HRT

Oral Micronized Progesterone (First Choice)

• Oral micronized progesterone (MP) is the first-line choice for HRT due to its physiological profile and safety advantages 1
• Standard dosing:
  • 200 mg daily for 12-14 days per 28-day cycle (sequential regimen) 1, 2
  • 100 mg daily for 25 days per month (continuous regimen) 3
• MP has been shown to minimize cardiovascular risks compared to synthetic progestogens and has a neutral or beneficial effect on blood pressure 1
• MP demonstrates one of the best safety profiles in terms of thrombotic risk 1

Alternative Progestogens (Second Choice)

• Medroxyprogesterone acetate (MPA): 10 mg daily for 12-14 days per month (sequential) or 2.5 mg daily (continuous) 1
• Dydrogesterone: 10 mg daily for 12-14 days per month (sequential) or 5 mg daily (continuous) 1
• Norethisterone: 5 mg daily for 12-14 days per month (sequential) or 1 mg daily (continuous) 1

Route of Administration Considerations

Transdermal Options

• Transdermal progesterone can be administered via combined patches with estrogen 1
• Example: Patches releasing 7 μg of levonorgestrel daily with 50 μg of 17β-estradiol 1
• Beneficial for patients with concerns about oral administration or first-pass metabolism 1

Vaginal Options

• Vaginal micronized progesterone: 200 mg daily for 12-14 days per month 1
• May be preferred in patients with gastrointestinal issues affecting oral absorption 1

Regimen Selection Based on Patient Needs

For Patients Desiring Regular Withdrawal Bleeding

• Sequential regimen: Estrogen continuously with progesterone added for 12-14 days per 28-day cycle 1
• Oral MP: 200 mg daily during the progesterone phase 1, 2
• MPA: 10 mg daily during the progesterone phase 1

For Patients Preferring Amenorrhea

• Continuous combined regimen: Estrogen and progesterone administered daily without interruption 1, 3
• Oral MP: 100 mg daily 3
• MPA: 2.5 mg daily 1
• Dydrogesterone: 5 mg daily 1

Special Considerations

Endometrial Protection

• The primary purpose of progesterone in HRT is endometrial protection 2
• Studies show that 200 mg of oral MP daily for 12 days per month with estrogen reduces the risk of endometrial hyperplasia from 64% to 6% compared to estrogen alone 2
• Lower doses (100 mg) may be sufficient for continuous regimens but suboptimal for sequential regimens 4, 3

Dose Adjustment Factors

• Adjust dose based on:
  • Patient's tolerance and feeling of wellbeing 1
  • Presence of breakthrough bleeding (may indicate need for dose adjustment) 1
  • History of endometriosis (may require higher doses) 1

Common Pitfalls to Avoid

• Using synthetic progestins in patients with cardiovascular risk factors (MP has better cardiovascular profile) 1
• Using progestins with anti-androgenic effects in patients with iatrogenic POI who may already have hypoandrogenism 1
• Inadequate progesterone dosing leading to insufficient endometrial protection 4
• Overlooking the need to continue HRT until the average age of natural menopause (45-55 years) 1

Monitoring

• Annual clinical review with attention to compliance 1
• No routine monitoring tests required unless prompted by specific symptoms 1
• Consider endometrial thickness assessment if breakthrough bleeding occurs 1

By following these evidence-based recommendations for progesterone dosing in HRT, clinicians can optimize both symptom management and endometrial protection while minimizing potential adverse effects.