Endometrial Hyperplasia – Current Nomenclature and Treatment

SUMMARY: 

Endometrial intraepithelial neoplasia (EIN) is the precursor of type I endometrioid adenocarcinoma. Distinguishing between hyperplasia and a precancerous lesion is important in optimizing management. 

Disease Categories  

• Benign endometrial hyperplasia (benign), a diffuse condition due to prolonged estrogen effect 
  • Treatment is hormonal therapy 
• Endometrial intraepithelial neoplasia (EIN) 
  • Premalignant 
  • Focal abnormality progressing to diffuse involvement  
  • Treatment can be hormonal therapy or surgery 
• Endometrial adenocarcinoma, endometrioid type, well differentiated (malignant), a focal abnormality progressing to diffuse 
  • Treatment is surgical 

Note: the above is the system developed by the International Endometrial Collaborative Group | Other classification systems exist and ACOG does not endorse a particular EIN classification system

Criteria Used for diagnosing EIN 

• Architectural change with area of glands greater than stroma 
• Cytologic abnormality in area of architectural change 
• Size of abnormal area  
• Not a polyp, area of repair, secretory endometrium (excludes mimics) 
• Not carcinoma (excludes cancer) 

Detecting Concurrent Carcinoma  

• Risk of endometrial cancer in hysterectomy specimens is 30% to 50%   
• Methods for Detecting Concurrent Carcinoma  
  • Hysteroscopic-guided uterine sampling is recommended for diagnosis  
  • In-office suction endometrial sampling may miss pathology  
• Avoid methods yielding crushed or cauterized samples  

Surgical Management of EIN  

• Hysterectomy is the definitive treatment   
• Supracervical hysterectomy is not advised   

Considerations for Oophorectomy  

• Oophorectomy decision should be patient-centered, weighing risks and benefits  
• Intraoperative assessment for occult carcinoma may guide surgical decisions  

Intraoperative Assessment  

• Assess uterine specimens for occult carcinoma   
• Assessment should be directed by qualified pathologists and experienced surgeons  
• Consultation with a gynecologic oncologist depending on clinical scenario and availability   

Morcellation – Proceed with Caution 

• If morcellation is required, use a contained environment such as a bag   
• Note that morcellation can affect pathology evaluation   

Endometrial Ablation  

• Not recommended   
• High persistence | Increased recurrence rates | May complicate evaluation of future bleeding episodes  

Nonsurgical Management of EIN 

Progestational Agents 

• Recommend progestational agents for patients not suitable for hysterectomy  
• LNG-IUD vs Oral Progestins  
  • Data on the superiority of administration methods are limited  
  • LNG-IUD may have a higher regression rate compared to oral progestins alone  
  • Combined intrauterine and oral progestins may be more effective  
• Oral Progestin Formulations  
  • No evidence favors one oral progestin formulation over another  
  • Megestrol acetate or medroxyprogesterone acetate are commonly used  
• Follow-up  
  • Repeat histologic assessment within 3 to 6 months for treatment response  
  • Long-Term Maintenance Therapy  
  • Consider long-term progestational agent maintenance for high-risk patients  
  • Consider risk factors (e.g., age, late menopause, and obesity)  
  • Optimal duration of maintenance therapy remains uncertain  

Future Fertility  

• Fertility-sparing therapy may be an option with assisted reproductive technology  
• Pregnancy rates range from 26.3% to 41.0% with progestational agents  
• Active management for achieving pregnancy should be discussed  

Counseling on Lifestyle Modifications  

• Weight Loss and Glycemic Control  
• Obesity is a significant risk factor   
• Lifestyle modification with weight loss and glycemic control improves overall health  
• Bariatric surgery can be an appropriate intervention among selected patients  
• Weight loss can enhance the response to progestin treatment  
• Telemedicine and Text-Based Interventions  

KEY POINTS: 

• The EIN system appears to increase reproducibility and reduce subjective, descriptive interpretation of pathology 
• Hysteroscopy with directed biopsy of any discrete lesions is the best way to confirm a premalignant endometrial lesion and to exclude endometrial carcinoma 
• Both suction curettage and dilation and curettage have significant sampling limitations 
• Hysterectomy is the definitive therapy for EIN: Abdominal, vaginal or minimally invasive, with or without removal of fallopian tubes and ovaries 
  • Supracervical hysterectomy is contraindicated 
  • Endometrial ablation should not be performed due to high recurrence rates and difficulty evaluating bleeding etiologies 
• Medical treatment, using progestins, can be offered to patients who wish to retain fertility, desire uterine retention, or have multiple medical comorbidities 
  • Medroxyprogesterone acetate and megestrol acetate are most commonly used 
  • The 52 mg levonorgestrel containing IUD provides another option 
  • Regression rates approach 90% with any of the above 
• Discussion of lifestyle changes particularly in the setting of obesity can be a part of management with shared decision making  
• Telemedicine and text-based interventions can assist patients with weight loss  

Learn More – Primary Sources 

Management of Endometrial Intraepithelial Neoplasia or Atypical Endometrial Hyperplasia | ACOG