Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early Stage Endometrial Cancer Medical Management

Globally, endometrial cancer is the sixth leading cause of female cancer-related deaths. Non-atypical endometrial hyperplasia (EH), has a lifetime progression rate to endometrial cancer ranging from less than 5%, if simple without atypia, to 40%, if complex with atypia. Site specific, long-acting intrauterine devices (IUDs) provide fertility sparing, progestin-based EH medical management. It is unclear which IUD is most beneficial, or if progesterone sensitizing metformin offers improved outcomes. For resolution, PubMed searches for "Mirena" or "Metformin," "treatment," "endometrial hyperplasia," or "stage 1 endometrial cancer," were performed, yielding 33 articles. Of these, 19 articles were included. The 60 mg high-dose frameless IUD/20 mcg levonorgestrel has achieved sustained regression of Grade 3 endometrial intraepithelial neoplasia for 14 years. Case series on early stage endometrial cancer (EC) treatment with IUDs have 75% or greater regression rates. For simple through complex EH with atypia, the 52 mg-IUD/10-20 mcg-LNG-14t has achieved 100% complete regression in 6-months. Clearly, IUDs have an outcome advantage over oral progestins. However, studies on metformin for EH, and of progestins or metformin for early stage EC management are underpowered, with inadequate dose ranges to achieve significant differences in, or optimal outcomes for, the treatment modalities. Therefore, outcomes from the feMMe trial for the 52 mg-IUD/10-20 mcg-LNG-14t and metformin will fill a gap in the literature.