What is the lowest dose of progesterone (Progesterone) allowed for use in Hormone Replacement Therapy (HRT)?

Lowest Dose of Progesterone for Hormone Replacement Therapy

The lowest effective dose of progesterone for endometrial protection in HRT is 100 mg daily when administered orally for 25 days per month in a continuous regimen, which has been shown to efficiently protect the endometrium and induce amenorrhea in most postmenopausal women. 1

Recommended Minimum Progesterone Dosages by Regimen Type

Sequential Regimens (with withdrawal bleeding)

• 200 mg oral micronized progesterone daily for 12-14 days per 28-day cycle is the standard recommended dose 2, 3
• 10 mg dydrogesterone daily for 12-14 days per month is an alternative option 4, 2
• 10 mg medroxyprogesterone acetate (MPA) daily for 12-14 days per month is another alternative 4, 2

Continuous Regimens (without withdrawal bleeding)

• 100 mg oral micronized progesterone daily for 25 days per month is the lowest effective dose for endometrial protection 1, 5
• Minimum effective doses for other progestins in continuous regimens:
  • 1 mg oral norethisterone daily 4, 6
  • 2.5 mg oral medroxyprogesterone acetate daily 4, 7
  • 5 mg oral dydrogesterone daily 4

Evidence for Endometrial Protection

• The FDA-approved clinical studies demonstrate that 200 mg of micronized progesterone daily for 12 days per 28-day cycle provides adequate endometrial protection when combined with estrogen, with only 6% of women developing hyperplasia compared to 64% in the estrogen-only group 3
• Research has shown that lower doses of 100 mg micronized progesterone daily for 25 days per month can effectively protect the endometrium by inhibiting mitoses and induces amenorrhea in over 90% of postmenopausal women 1, 5
• Continuous low-dose progestogen regimens require careful monitoring as inadequate dosing has been associated with cases of endometrial hyperplasia and carcinoma 7

Factors Affecting Dose Selection

• Micronized progesterone is the preferred choice due to its lower risk of cardiovascular disease and venous thromboembolism compared to synthetic progestins 4, 2
• Route of administration affects bioavailability:
  • Oral administration requires higher doses due to first-pass metabolism 5
  • Vaginal administration of 200 mg micronized progesterone is an alternative route with good endometrial protection 4, 2
• Treatment goals influence dosing:
  • For women seeking amenorrhea, continuous regimens with lower doses may be preferred 8
  • For women preferring cyclic withdrawal bleeding, sequential regimens are appropriate 2

Special Populations

• For adolescents with premature ovarian insufficiency (POI), begin cyclic progestogens after at least 2 years of estrogen therapy or when breakthrough bleeding occurs 4
• For adolescents, recommended doses include:
  • Oral micronized progesterone 100-200 mg/day during 12-14 days of the month 4
  • Dydrogesterone 5-10 mg/day during 12-14 days of the month 4
• For women with POI, treatment should continue until the average age of natural menopause (45-55 years) 4, 2

Clinical Considerations and Monitoring

• Adjust progesterone dose according to the woman's tolerance and feeling of wellbeing 4, 2
• Annual clinical review is recommended to assess compliance and side effects 2
• The most common side effect of micronized progesterone is mild and transient drowsiness, which can be minimized by taking the medication at bedtime 5
• Continuous regimens with lower doses of progestogen have been associated with fewer side effects such as mastalgia compared to higher doses 8

Remember that while 100 mg of micronized progesterone daily for 25 days per month represents the lowest effective dose for endometrial protection, the standard recommended dose in most guidelines is 200 mg daily for 12-14 days per month in sequential regimens 2, 3, 5.