METABOLIC AND HORMONAL RISK FACTORS FOR ENDOMETRIAL HYPERPLASIA IN REPRODUCTIVE-AGE WOMEN: A CRITICAL INTEGRATIVE REVIEW OF PATHOBIOLOGY, REAL-WORLD EVIDENCE AND PRECISION RISK ASSESSMENT

Endometrial  hyperplasia  in  reproductive-age  women  encompasses  biologically  heterogeneous  lesions  whose  risk  is  shaped  by  chronic  anovulation,  unopposed  estrogen  exposure,  adiposity,  insulin  resistance,  diabetes  and  associated  inflammation.  The  clinical  distinction  between  hyperplasia  without  atypia  and  endometrial intraepithelial neoplasia/atypical endometrial hyperplasia (EIN/AEH) is  essential  because  the  latter  can  coexist  with  or  precede  carcinoma.  Objective:  To  critically integrate mechanistic, clinical and regulatory evidence linking metabolic and  hormonal exposures to endometrial proliferative disorders and to propose a transparent  real-world  research  framework.  Methods: