What is the recommended progesterone (progestin) therapy regimen for postmenopausal women?

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Recommended Progesterone Therapy Regimen for Postmenopausal Women

For postmenopausal women with an intact uterus who are taking estrogen therapy, oral micronized progesterone at a dose of 200 mg daily for 12 days per 28-day cycle is the recommended progesterone regimen. 1, 2

Evidence-Based Recommendations

Standard Regimen

  • Oral micronized progesterone: 200 mg daily at bedtime for 12 consecutive days per 28-day cycle 1
    • Must be taken with estrogen therapy to prevent endometrial hyperplasia
    • Should be taken at bedtime due to potential drowsiness
    • Take with a glass of water while standing if swallowing difficulties occur

Alternative Regimens

  • Continuous combined regimen: Medroxyprogesterone acetate 2.5 mg daily with daily estrogen 2
  • Sequential regimen: Medroxyprogesterone acetate 10 mg daily for 10-14 days per month with daily estrogen 3

Clinical Considerations

Safety Profile

  • Micronized progesterone is preferred over synthetic progestins due to:
    • Lower cardiovascular risk 2
    • Lower thromboembolism risk 2
    • Potentially lower breast cancer risk 4

Route of Administration

  • Transdermal estradiol (50-100 μg/day) combined with oral micronized progesterone offers the safest HRT profile for:
    • Women with cardiovascular risk factors
    • Those at risk for venous thromboembolism
    • Older women (>60 years) 2

Duration of Therapy

  • Use the lowest effective dose for the shortest time necessary 5
  • Approximately 75% of women can discontinue HRT without major difficulty 5
  • For women who cannot tolerate discontinuation, the symptom relief value may outweigh risks 5

Monitoring

  • Initial follow-up every 1-3 months to assess symptom control and bleeding patterns 2
  • Annual gynecological assessment including pelvic examination 2
  • Monitor for:
    • Irregular vaginal bleeding
    • Signs of thromboembolism
    • Cardiovascular events

Important Cautions

  • HRT with estrogen plus progestin should not be recommended for secondary prevention of coronary disease 3
  • Combined estrogen-progestin therapy is associated with increased risk of:
    • Venous thromboembolism (RR 2.89; 95% CI, 1.50 to 5.58) 3
    • Gallbladder disease (RR 1.38; 95% CI, 1.00 to 1.92) 3
    • Potential increased risk of breast cancer with >5 years of use 4

Special Populations

  • Women who have had a hysterectomy: Do not require progesterone therapy with estrogen 3, 2
  • Women with history of breast cancer: Avoid combined estrogen-progestin therapy 2
  • Smokers over 35: Use with caution due to increased cardiovascular risk 2

Remember that progesterone therapy is specifically indicated for endometrial protection in women with an intact uterus who are taking estrogen therapy. The FDA-approved indication for progesterone capsules is prevention of endometrial hyperplasia in postmenopausal women with a uterus who are receiving concomitant estrogen therapy 1.

References

Guideline

Hormone Replacement Therapy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The impact of micronized progesterone on breast cancer risk: a systematic review.

Climacteric : the journal of the International Menopause Society, 2018

Research

Discontinuation of postmenopausal hormone therapy.

The American journal of medicine, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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