What is the management approach for endometrial hyperplasia with bleeding?

Management of Endometrial Hyperplasia with Bleeding

For endometrial hyperplasia with bleeding, the management depends critically on whether atypia is present: hyperplasia without atypia should be treated with continuous progestin therapy (medroxyprogesterone acetate 400-600 mg/day or megestrol acetate 160-320 mg/day, or levonorgestrel-IUD), while atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) requires hysterectomy as definitive treatment unless fertility preservation is desired. 1, 2

Initial Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis and classification through proper tissue sampling:

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

Management Algorithm Based on Histologic Classification

For Hyperplasia WITHOUT Atypia:

First-line medical therapy with continuous progestins:

• Levonorgestrel-IUD (LNG-IUS) is preferred over oral progestins, with higher regression rates (>90%), lower recurrence rates, and fewer adverse events 3, 2
• Alternative oral regimens: Medroxyprogesterone acetate 400-600 mg/day OR megestrol acetate 160-320 mg/day 1, 2
• Continue treatment until two consecutive negative endometrial biopsies are obtained 3, 2

Monitoring protocol:

• Perform endometrial biopsy or D&C every 6 months during treatment to assess response 2, 3
• If hyperplasia persists after 6-12 months of progestin therapy, proceed to hysterectomy 2

For Atypical Hyperplasia/EIN (AH/EIN):

Hysterectomy is the definitive treatment due to 50% risk of concurrent endometrial cancer and high progression rates 2, 1

• Perform total hysterectomy with bilateral salpingo-oophorectomy 2, 1
• Minimally invasive approach is appropriate 3
• No indication for lymphadenectomy for hyperplasia with or without atypia 3

Fertility preservation (highly selected cases only):

• Mandatory referral to specialized centers for patients desiring fertility preservation with AH/EIN 1, 2
• Use medroxyprogesterone acetate 400-600 mg/day OR megestrol acetate 160-320 mg/day (LNG-IUD with or without GnRH analogues can also be considered) 1, 2
• Complete response occurs in approximately 50% of patients, but recurrence rates remain 30-40% even after initial response 1, 2
• Perform endometrial biopsy every 3 months during conservative treatment 2, 3
• If no response after 6 months, proceed to hysterectomy 1, 2
• After achieving complete response, encourage immediate conception through assisted reproductive technologies if needed 1, 2
• After completion of childbearing, hysterectomy with bilateral salpingo-oophorectomy is mandatory 1, 2

Contraindications to Progestin Therapy

Do not prescribe progestins in patients with: 4, 2

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

Management of Acute Bleeding

For patients presenting with active bleeding:

• If medical treatment fails to control bleeding, further investigation with hysteroscopy is indicated to visualize the endometrial cavity and diagnose focal lesions possibly missed by sampling 1
• Hysteroscopy allows direct visualization to distinguish between diffuse hyperplasia, polyps, and submucosal fibroids that may be contributing to bleeding 1, 5

Critical Pitfalls to Avoid

• Never accept inadequate or non-diagnostic tissue sampling in a patient with persistent bleeding—the false-negative rate of office endometrial biopsy is approximately 10%, requiring escalation to D&C under anesthesia if clinical suspicion remains high 5, 2
• Do not use progestin therapy for high-grade histologies (serous, clear cell, carcinosarcoma)—these require immediate surgical staging 2
• Do not offer fertility preservation without comprehensive counseling that this is non-standard treatment with 50% failure rates and 30-40% recurrence rates 1, 2
• Never perform inadequate follow-up—failure to perform endometrial sampling every 3-6 months can result in undetected progression to carcinoma 2, 3

Special Populations

For women with Lynch syndrome:

• Continue annual endometrial biopsy surveillance starting at age 30-35 years regardless of treatment, as these patients have 30-60% lifetime risk of endometrial cancer 5, 2
• Discuss prophylactic hysterectomy and bilateral salpingo-oophorectomy at age 40 2