Prometrium HRT Dosing
For hormone replacement therapy, Prometrium (micronized progesterone) should be dosed at 200 mg orally daily for 12-14 days per 28-day cycle when used in a sequential regimen with estrogen, or 100 mg daily for continuous regimens, with micronized progesterone preferred over synthetic progestins due to superior cardiovascular and thrombotic safety profiles. 1, 2, 3
Sequential Regimen (Preferred for Women Accepting Withdrawal Bleeding)
Standard dosing:
- 200 mg oral micronized progesterone daily for 12-14 consecutive days every 28-day cycle 1, 2, 3
- Administered continuously with transdermal 17β-estradiol (50-100 μg daily) 1, 4
- This regimen provides complete endometrial protection with only 6% incidence of hyperplasia versus 64% with estrogen alone 3
Alternative sequential options if micronized progesterone not tolerated:
- Medroxyprogesterone acetate 10 mg daily for 12-14 days per month 1, 2
- Dydrogesterone 10 mg daily for 12-14 days per month 1, 2
Continuous Regimen (For Women Preferring Amenorrhea)
Minimum effective doses:
- Micronized progesterone 100 mg daily without interruption 2
- Medroxyprogesterone acetate 2.5 mg daily 2
- Dydrogesterone 5 mg daily 2
- Norethisterone 1 mg daily 2
The continuous regimen achieves amenorrhea in 73-83% of women by 2 years 5, 6
Alternative Administration Routes
Vaginal administration:
- 200 mg micronized progesterone vaginally for 12-14 days per month provides equivalent endometrial protection with potentially fewer systemic side effects 2, 7
- Vaginal progesterone gel (Crinone 4% or 8%) every other day for 6 doses per month achieved progestational changes in 92-100% of patients 8
- Twice-weekly vaginal progesterone (45 mg/day) with transdermal estradiol resulted in 82% amenorrhea and 92% endometrial atrophy 6
Critical Selection Factors
Micronized progesterone is the first-line choice because:
- Lower cardiovascular disease risk compared to synthetic progestins 1, 2
- Lower venous thromboembolism risk when used cyclically 1, 2
- Better metabolic profile and lower breast cancer risk 1
- The only specific side effect is mild transient drowsiness, minimized by bedtime dosing 9
Avoid progestins with anti-androgenic effects in women with diminished libido or sexual dysfunction 1
Monitoring and Adjustment
Initial assessment:
- Clinical review at 3 months to assess symptom improvement, side effects, and compliance 1
- Common side effects (mood changes, breast tenderness, bloating, breakthrough bleeding) typically resolve within 3 months 1
- No routine monitoring tests required unless specific symptoms develop 1, 2
Long-term management:
- If significant side effects persist beyond 6 months, switch to alternative progesterone formulation or adjust dosing regimen 1
- Annual clinical review to assess compliance and side effects 2
- Adjust dose according to tolerance and wellbeing 2
Special Populations
Women with premature ovarian insufficiency:
- Continue treatment until average age of natural menopause (45-55 years) 2, 4
- For adolescents with POI, begin cyclic progestogens after at least 2 years of estrogen therapy or when breakthrough bleeding occurs 2
Women with cardiovascular risk factors:
- Strongly prefer micronized progesterone over medroxyprogesterone acetate 4
- Transdermal estradiol preferred over oral formulations due to avoidance of first-pass hepatic metabolism and lower thromboembolism risk 4
Common Pitfalls to Avoid
- Do not use unopposed estrogen in women with intact uterus - this increases endometrial hyperplasia risk from baseline 3% to 64% 3
- Do not use progesterone for fewer than 10 days per month in sequential regimens - inadequate endometrial protection 9
- Do not discontinue therapy prematurely due to initial breakthrough bleeding - this typically resolves within 3 months 1