Aygestin (Norethisterone Acetate) After Endometrial Biopsy
Direct Answer
Aygestin is indicated after endometrial biopsy when the pathology shows endometrial hyperplasia without atypia, using a dose of 15 mg/day for 10 days per cycle for 3-6 months, with mandatory repeat endometrial sampling every 3-6 months to assess response. 1, 2
Specific Indications Based on Biopsy Results
For Non-Atypical Endometrial Hyperplasia (Simple or Complex Without Atypia)
- Aygestin (norethisterone/NET) 15 mg/day for 10 days per cycle is an appropriate first-line oral progestin option 1, 3
- Alternative oral progestins include medroxyprogesterone acetate (MPA) 10 mg/day for 10 days per cycle or megestrol acetate 160-320 mg/day continuously 1, 2
- Research shows norethisterone achieves a 37-40% resolution rate after 3 months of treatment 3, 4
For Atypical Hyperplasia/Endometrial Intraepithelial Neoplasia (AH/EIN)
- Aygestin is NOT the preferred oral progestin for atypical hyperplasia 1
- If oral progestins are used for AH/EIN (fertility preservation only), higher doses are required: medroxyprogesterone acetate 400-600 mg/day or megestrol acetate 160-320 mg/day 1, 2
- Mandatory referral to specialized centers is required before initiating treatment 1, 2
- Hysterectomy with bilateral salpingo-oophorectomy remains the definitive treatment for atypical hyperplasia 1
When Aygestin Should NOT Be Used
- Aygestin is contraindicated if biopsy shows any grade of endometrial cancer, cervical cancer, or high-risk histologies 1, 5
- Do not use in patients with history of breast cancer, stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, or active smoking 1, 2
Treatment Protocol and Duration
Initial Treatment Course
- Start with 15 mg/day for 10 days per menstrual cycle (cyclic regimen) 3, 4
- Continue for minimum 3 months before first reassessment 1, 6
- Perform endometrial biopsy or dilation and curettage at 3 months to evaluate response 1, 2
Response-Based Management Algorithm
If complete resolution (normal endometrium):
- Consider stopping treatment but maintain surveillance 6
- Risk of recurrence is 30-40% even after complete response 1
If regression (downgraded to proliferative endometrium) or persistence:
If no response after 6 months or progression:
- Switch to alternative progestin (megestrol acetate 160-320 mg/day or MPA 400-600 mg/day) 2
- Consider levonorgestrel-releasing intrauterine device (LNG-IUD), which shows superior efficacy (66.67% resolution rate vs 40% for norethisterone) 4
- Proceed to hysterectomy if no response after 6-12 months total treatment 1, 2
Mandatory Follow-Up Requirements
Surveillance Schedule
- Endometrial biopsy or D&C every 3-6 months during active treatment 1, 2
- More frequent sampling (every 3 months) is recommended for higher-grade lesions 1
- Treatment should continue for minimum 6 months before declaring treatment failure, as architectural changes resolve later than cytologic changes 7
Pathologic Assessment Criteria
- Complete response: normal endometrium with no hyperplasia 7, 8
- Partial response: regression to simple hyperplasia without atypia 8
- Persistent architectural abnormalities and/or cytologic atypia at 7-9 months predict treatment failure 7
Critical Caveats and Common Pitfalls
Before Starting Treatment
- Confirm diagnosis with expert gynaecopathologist review to exclude hidden atypia or cancer 1, 2
- Perform pelvic MRI if considering conservative management to exclude myometrial invasion 1, 2
- Evaluate for associated pelvic pathology (fibroids, polyps, adenomyosis), as 84.6% of clinical non-responders have concurrent pelvic disease 6
During Treatment
- Clinical non-response (persistent abnormal bleeding during first 4 months) strongly suggests associated pelvic pathology requiring further evaluation 6
- Do not rely solely on clinical response; pathologic confirmation is mandatory 6
- Progestin therapy may induce cribriform and papillary architectural patterns that mimic progression—these are treatment effects, not true progression 7
Special Populations
- Women with Lynch syndrome require annual surveillance starting at age 35 and should discuss prophylactic hysterectomy at age 40 1
- Fertility preservation patients must understand this is non-standard treatment with 50% response rate and 35% recurrence risk 1
- After completion of childbearing, hysterectomy with bilateral salpingo-oophorectomy is strongly recommended 1, 2
Comparative Efficacy of Treatment Options
Oral Progestins Head-to-Head
- Norethisterone (NET) 15 mg/day: 37-40% resolution rate 3, 4
- Medroxyprogesterone acetate (MPA) 10 mg/day: 36.7% resolution rate 3
- Lynestrenol 15 mg/day: 56% resolution rate (highest among cyclic oral progestins) 3
- No statistically significant difference between these oral progestins at standard doses for non-atypical hyperplasia 3