What is the recommended dose of progesterone for hormone replacement therapy (HRT)?

Recommended Progesterone Dosing for Hormone Replacement Therapy

For women with an intact uterus requiring hormone replacement therapy (HRT), the standard recommended dose of oral micronized progesterone is 200 mg daily for 12-14 days per 28-day cycle when combined with estrogen therapy. 1

Progesterone Options and Dosing

Oral Micronized Progesterone

• Standard dose: 200 mg daily for 12-14 days per month in a sequential regimen 1
• Continuous regimen option: 100 mg daily for 25 days per month (for women preferring amenorrhea) 2
• Maximum effectiveness: 300 mg daily has been shown to achieve physiological endometrial responses 3

Administration Regimens

1. Sequential regimen (with withdrawal bleeding):

   • Progesterone 200 mg daily for 12-14 days per 28-day cycle 4, 1
   • Allows for earlier recognition of pregnancy in women with POI who may spontaneously ovulate 5

2. Continuous regimen (to prevent withdrawal bleeding):

   • Progesterone 100 mg daily for 25 days per month 2
   • Achieves amenorrhea in over 90% of women, potentially improving long-term compliance 2

Progesterone Type Selection

Natural Micronized Progesterone (MP)

• First choice due to favorable safety profile 5
• Benefits compared to synthetic progestins:
  • Minimizes cardiovascular risks 5
  • Neutral or beneficial effect on blood pressure 5
  • Better safety profile for thrombotic risk 5
  • Fewer metabolic side effects 6
  • Improved cognitive outcomes compared to MPA 7

Medroxyprogesterone Acetate (MPA)

• Alternative option with extensive efficacy data 5
• 5-10 mg daily for 12-14 days per month 4
• Potential drawbacks:
  • May negatively impact cardiovascular risk factors 5
  • Less favorable effects on lipid profiles and vasomotion 5

Clinical Efficacy and Endometrial Protection

The FDA-approved clinical trials demonstrate that progesterone 200 mg daily for 12 days per 28-day cycle, when combined with conjugated estrogens 0.625 mg daily, significantly reduces the risk of endometrial hyperplasia compared to estrogen alone (6% vs 64% hyperplasia rate over 36 months) 1.

Monitoring and Side Effects

Common Side Effects

• Headache (31%)
• Breast tenderness (27%)
• Joint pain (20%)
• Depression (19%)
• Dizziness (15%) 1

Important Considerations

• Take progesterone at bedtime to minimize drowsiness 6
• Regular clinical review (every 3-6 months initially, then annually) to assess symptom control and side effects 4
• Ensure adequate endometrial protection with appropriate dosing

Special Situations

• Women seeking amenorrhea: Consider continuous regimen with 100 mg daily for 25 days per month 2
• Women with cardiovascular risk factors: Natural micronized progesterone preferred over synthetic progestins 5
• Women with sleep disturbances: Bedtime administration may be beneficial due to mild sedative effects 6

Pitfalls to Avoid

1. Inadequate endometrial protection: Using too low a dose or too short a duration increases risk of endometrial hyperplasia
2. Ignoring cardiovascular risk: Synthetic progestins may have less favorable cardiovascular effects than natural progesterone
3. Overlooking compliance issues: Consider patient preference for bleeding patterns when selecting regimen
4. Missing contraindications: Progesterone is contraindicated in women with current or past history of thromboembolism, undiagnosed vaginal bleeding, or hormone-dependent cancers

Remember that the dose of progesterone should be matched to the concurrent dose of estrogen to ensure adequate endometrial protection 5.