Is continuous use of micronized bioidentical progesterone (micronized bioidentical progesterone) more effective than cyclic use in reducing hyperplastic endometrium?

Continuous Micronized Progesterone for Endometrial Hyperplasia

For treatment of endometrial hyperplasia, continuous progesterone regimens provide superior endometrial protection compared to cyclic regimens, and you should use continuous daily dosing rather than cyclic therapy with breaks. 1, 2

Evidence for Continuous vs. Cyclic Regimens

Endometrial Protection Profile

• Continuous combined treatment confers better protection against endometrial hyperplasia and cancer than sequential/cyclic regimens, regardless of which progestogen is used 2
• For fertility-sparing treatment of grade 1 endometrial cancer and endometrial hyperplasia, NCCN guidelines specifically recommend continuous progestin-based therapy (not cyclic) 1
• The protective effect against hyperplasia is affected by regimen type and dose, with continuous administration providing superior outcomes 2

Treatment Efficacy Data

• Continuous medroxyprogesterone acetate (10 mg daily) for 6 weeks or cyclic administration (10 mg daily for 2 weeks per month for 3 months) both achieve >90% reversal rates of estrogen-induced endometrial hyperplasia 3
• However, for established hyperplasia requiring treatment, continuous regimens are preferred based on guideline recommendations for endometrial cancer prevention 1

Specific Dosing Recommendations for Hyperplasia Treatment

Micronized Progesterone Options

• 200 mg oral micronized progesterone daily continuously is the evidence-based dose for endometrial protection in continuous regimens 4, 5
• For cyclic treatment of non-atypical hyperplasia, 200 mg daily for 12-14 days per month achieved 97.5% remission in simple hyperplasia and 92.4% in complex hyperplasia 5
• 100 mg daily vaginal micronized progesterone for 16 days per cycle (days 10-25) achieved 90.5% complete regression of benign endometrial hyperplasia 6

Alternative Continuous Regimens

• Medroxyprogesterone acetate 2.5 mg daily continuously 4
• Dydrogesterone 5 mg daily continuously 4
• Norethisterone 1 mg daily continuously 4

Clinical Implementation Strategy

For Active Hyperplasia Treatment

• Use continuous daily progesterone without breaks - this is the standard approach for fertility-sparing therapy in endometrial cancer and hyperplasia 1
• Perform endometrial sampling every 3-6 months to monitor response 1
• If hyperplasia persists after 6-12 months of continuous therapy, consider surgical management 1

Monitoring Requirements

• Endometrial biopsy or D&C every 3-6 months during treatment 1
• Document complete regression before considering any change in regimen 1
• After regression, continue treatment until definitive surgical management or completion of fertility goals 1

Important Caveats

Contraindications to Consider

• Screen for contraindications including breast cancer, stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, and smoking status 1
• Micronized progesterone has the most favorable cardiovascular and thrombotic risk profile compared to synthetic progestins 4, 2

When Cyclic Regimens Are Appropriate

• Cyclic regimens (12-14 days per month) are appropriate for prevention of hyperplasia in women on estrogen replacement therapy who desire regular withdrawal bleeding 4, 7
• For treatment of established hyperplasia, continuous therapy is superior 1, 2

Recurrence Risk

• After successful regression with cyclic progesterone, recurrence rates of 1.7% at 3 months and 6.1% at 6 months have been reported 6
• This supports the use of continuous rather than cyclic therapy for active disease management 2