What is the recommended treatment approach for a patient with acute endometrial hyperplasia to reduce the risk of progression to endometrial cancer?

Treatment of Acute Endometrial Hyperplasia

For endometrial hyperplasia without atypia, continuous oral progestins (medroxyprogesterone acetate 400-600 mg/day or megestrol acetate 160-320 mg/day) are the recommended first-line treatment, while atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) requires hysterectomy with bilateral salpingo-oophorectomy as definitive treatment due to the 50% risk of concurrent endometrial cancer. 1, 2

Initial Diagnostic Confirmation Required

Before initiating any treatment, proper classification is essential:

• Obtain dilatation and curettage (D&C) rather than pipelle biopsy for accurate grading, as D&C is superior for determining the presence of atypia 2, 3
• Require expert gynaecopathologist review to reliably distinguish hyperplasia without atypia from AH/EIN, as this distinction determines whether medical versus surgical management is appropriate 2, 3
• Perform pelvic MRI to exclude myometrial invasion if conservative management is being considered, as occult invasion would change management to surgical staging 1, 2

Treatment Algorithm Based on Histologic Classification

For Hyperplasia WITHOUT Atypia (Non-Atypical Endometrial Hyperplasia):

Medical Management:

• Medroxyprogesterone acetate 400-600 mg/day orally (continuous) OR megestrol acetate 160-320 mg/day orally (continuous) 1, 2, 4
• Levonorgestrel-releasing intrauterine device (LNG-IUD) is an acceptable alternative option 1, 2
• Continue treatment until two consecutive negative endometrial biopsies are obtained 3
• Perform endometrial sampling every 3-6 months during treatment to monitor response 2

Response rates: Approximately 50-75% complete response rate with progestin therapy for non-atypical hyperplasia 2, 5

Long-term progression risk: Less than 5% risk of progression to carcinoma if untreated 5

For Atypical Hyperplasia/Endometrial Intraepithelial Neoplasia (AH/EIN):

Definitive Surgical Management (Standard of Care):

• Total hysterectomy with bilateral salpingo-oophorectomy is the recommended definitive treatment 1, 2
• This eliminates both the existing atypical hyperplasia and the risk of progression to endometrial cancer 2
• Rationale: 50% risk of concurrent endometrial cancer at time of diagnosis and approximately 30% risk of progression to carcinoma if untreated 2, 5

Fertility-Sparing Management (Highly Selected Cases Only):

This is non-standard treatment and requires meeting ALL of the following strict criteria 1, 2:

• Mandatory referral to specialized centers for management 1, 2
• Diagnosis confirmed by expert gynaecopathologist to exclude concurrent carcinoma 1, 2
• Pelvic MRI performed to exclude myometrial invasion and adnexal involvement 1, 2
• Patient fully informed that this is non-standard treatment with significant risks 1, 2
• Patient accepts close follow-up with frequent endometrial sampling 2

Progestin regimens for fertility preservation:

• Medroxyprogesterone acetate 400-600 mg/day orally (continuous) OR megestrol acetate 160-320 mg/day orally (continuous) 1, 2
• Levonorgestrel-releasing intrauterine device is also an option 1
• Complete response occurs in approximately 50% of patients 2
• Recurrence rate is 30-40% even after initial complete response 2

After completion of childbearing: Hysterectomy with bilateral salpingo-oophorectomy is strongly recommended to eliminate future cancer risk 1, 2

Monitoring Protocol During Medical Management

• Endometrial sampling every 3-6 months during progestin treatment, with more frequent sampling for atypical hyperplasia 2
• If hyperplasia persists after 6-12 months of progestin therapy, proceed to hysterectomy 2
• Never accept an inadequate or negative endometrial biopsy as reassuring in a symptomatic patient—office endometrial biopsies have a 10% false-negative rate 3, 6

Critical Contraindications to Progestin Therapy

Progestins are contraindicated in patients with 2, 7:

• History of breast cancer
• History of stroke or myocardial infarction
• Active smoking
• History of pulmonary embolism or deep vein thrombosis

Special Populations Requiring Modified Approach

Women with Lynch Syndrome:

• Annual surveillance with gynecological examination, transvaginal ultrasound, and endometrial biopsy starting from age 30-35 years 2, 3
• 30-60% lifetime risk of endometrial cancer 3, 6
• Prophylactic hysterectomy and bilateral salpingo-oophorectomy should be discussed at age 40 2

Common Pitfalls to Avoid

1. Do not use progestin therapy for high-risk histologies such as high-grade endometrioid adenocarcinomas, uterine serous carcinoma, clear cell carcinoma, carcinosarcoma, or leiomyosarcoma 2

2. Do not accept negative biopsy results in symptomatic patients without further evaluation—proceed to fractional D&C or hysteroscopy if symptoms persist 3, 6

3. Do not delay hysterectomy in patients with AH/EIN who are not candidates for fertility preservation or who have failed medical management after 6-12 months 2

4. Do not perform inadequate follow-up—failure to perform endometrial sampling every 3-6 months can lead to undetected progression to carcinoma 2

5. Do not initiate hormonal therapy before obtaining tissue diagnosis in patients with abnormal bleeding and thickened endometrium 6