What are the differentials and management options for endometrial hyperplasia?

Endometrial Hyperplasia: Differentials and Management

The management of endometrial hyperplasia depends primarily on the presence of atypia, with progestin therapy recommended for hyperplasia without atypia and hysterectomy recommended for atypical hyperplasia, except in cases where fertility preservation is desired. 1

Differential Diagnosis

Classification

• Endometrial hyperplasia without atypia (benign)
• Atypical hyperplasia/endometrial intraepithelial neoplasia (EIN) 2

Common Presentations

• Abnormal uterine bleeding (most common symptom) 3
• Incidental finding on imaging or endometrial biopsy
• Postmenopausal bleeding

Risk Factors

• Unopposed estrogen exposure 2
• Polycystic ovary syndrome
• Tamoxifen use
• Hormone replacement therapy without progesterone
• Obesity
• Nulliparity
• Late menopause

Diagnostic Approach

Imaging

• Transvaginal ultrasound (first-line imaging) 3
• Transrectal ultrasound (for virgins) 3

Histological Confirmation

• Diagnostic curettage
• Hysteroscopic-guided biopsy
• Endometrial aspiration biopsy 3

Management Algorithm

Endometrial Hyperplasia Without Atypia

1. First-line treatment: Progestin therapy 1

   • Levonorgestrel-releasing intrauterine system (LNG-IUS) preferred due to:
     • Higher regression rates
     • Lower recurrence rates
     • Fewer adverse events 3
   • Oral options:
     • Medroxyprogesterone acetate
     • Megestrol acetate 1

2. Monitoring

   • Endometrial sampling every 6 months during treatment 3
   • Continue treatment until no pathological changes observed in two consecutive biopsies 3

3. Treatment failure

   • Consider hysterectomy if:
     • Persistence after 6-12 months of therapy
     • Disease progression documented 1

Atypical Hyperplasia/EIN

1. First-line treatment: Minimally invasive hysterectomy with bilateral salpingectomy 3

   • No indication for sentinel lymph node biopsy or lymphadenectomy 3

2. Fertility-preserving options (for women <45 years or desiring fertility) 3

   • LNG-IUS preferred 3
   • Oral progestins as alternative
   • Monitoring:
     • Endometrial sampling every 3 months 3
     • Continue until no pathological changes in two consecutive biopsies 3
   • After regression:
     • Assisted reproductive technologies recommended 3
     • Hysterectomy after childbearing is complete 4

3. Recurrent atypical hyperplasia

   • Total hysterectomy recommended 3
   • Consider conservative therapy only for fertility preservation 3

Special Considerations

Contraindications to Progestin Therapy

Exercise caution in patients with history of:

• Breast cancer
• Stroke or myocardial infarction
• Pulmonary embolism or deep vein thrombosis
• Active smoking 1

Fertility Preservation

For young women with grade 1 endometrioid adenocarcinoma or atypical hyperplasia desiring fertility preservation:

• Referral to specialized centers
• Diagnostic curettage with/without hysteroscopy
• Pelvic MRI to exclude myometrial invasion
• Informed consent regarding non-standard treatment
• Close follow-up 4

Long-term Follow-up

• Recommended for all patients after treatment 3
• Patient education improves medication adherence, increases regression rates, and lowers recurrence rates 3

Treatment Outcomes

• Approximately 50% of patients treated with progestin therapy experience a durable complete response 1
• Higher success rates with LNG-IUS compared to oral progestins 3

Remember that untreated atypical hyperplasia has significant risk of progression to or coexistence with endometrial carcinoma, making appropriate management crucial for reducing morbidity and mortality.