Treatment for Non-Atypical Endometrial Hyperplasia
Oral progestin therapy with medroxyprogesterone acetate (MPA) or megestrol acetate (MA) is the recommended first-line treatment for non-atypical endometrial hyperplasia, with levonorgestrel-releasing intrauterine device (LNG-IUD) as an alternative option. 1
Initial Management Approach
Diagnostic Confirmation Required
- Histological confirmation through endometrial biopsy is mandatory before initiating treatment, preferably by dilatation and curettage (D&C) rather than pipelle biopsy for accurate grading 1
- Review by an expert gynaecopathologist is essential to confirm the diagnosis and exclude atypical hyperplasia 1
- Pelvic MRI should be performed if conservative management is being considered to exclude myometrial invasion 1
First-Line Treatment Options
Oral Progestin Regimens:
- Megestrol acetate 160-320 mg/day is the recommended dosage 1
- Medroxyprogesterone acetate 400-600 mg/day may be used as an alternative 1
- Natural progesterone 200 mg daily (cyclic administration) has shown 97.5% remission rates for simple hyperplasia and 92.4% for complex hyperplasia 2
Levonorgestrel Intrauterine Device:
- LNG-IUD releasing 20 mcg/day is an effective alternative option 1, 3
- All patients in one long-term study developed normal endometrium with LNG-IUD treatment 3
- This option provides local delivery with profound endometrial suppression 3
Monitoring Protocol
Surveillance Schedule
- Endometrial sampling every 3-6 months during treatment is mandatory 1
- Evaluation of response should occur at 6 months via endometrial biopsy or D&C 1
- Continue surveillance until complete regression is documented 1
Treatment Duration and Response
- Complete response occurs in approximately 50-75% of patients with progestin therapy 1
- If hyperplasia persists after 6-12 months of progestin therapy, proceed to hysterectomy 1
- Recurrence rates remain 30-40% even after initial complete response 1
When to Proceed to Surgery
Hysterectomy with bilateral salpingo-oophorectomy should be performed in:
- Postmenopausal patients with endometrial cancer risk factors 4
- Persistent non-atypical hyperplasia despite 6-12 months of medical therapy 1, 4
- Patients with contraindications to progesterone therapy 4
- Documented progression to atypical hyperplasia or cancer 1
Critical Contraindications to Progestin Therapy
Absolute contraindications include: 1
- History of breast cancer
- History of stroke or myocardial infarction
- Active smoking
- History of pulmonary embolism or deep vein thrombosis
Special Populations
Postmenopausal Women
- Regular re-examination during conservative treatment is essential 4
- Lower threshold for surgical management due to higher progression risk 4
- Hysterectomy should be strongly considered as first-line treatment in this population 4
Women Desiring Fertility Preservation
- Referral to specialized centers is mandatory 1
- Patients must be fully informed that fertility-sparing treatment is non-standard 1
- After completion of childbearing, hysterectomy and bilateral salpingo-oophorectomy is recommended 1
Common Pitfalls to Avoid
- Inadequate follow-up: Failure to perform endometrial sampling every 3-6 months can lead to undetected progression to atypical hyperplasia or carcinoma 1
- Insufficient treatment duration: Stopping therapy before 6 months without documented complete response increases recurrence risk 1
- Missing contraindications: Always screen for history of thromboembolic events, cardiovascular disease, and breast cancer before initiating progestin therapy 1
- Inadequate initial workup: Failing to obtain expert pathology review may result in missed atypical hyperplasia, which requires different management 1