Conservative treatment for atypical endometrial hyperplasia: what is the most effective therapeutic method?

especially in the presence of atypia, has a strong tendency to the development of endo-metrial carcinoma. In this respect, hysterectomy is a preferred treatment for atypical EH. However, for young patient who desire to preserve their fertility or for patients not selected for surgery, conservative treatments using progestin are widely accepted as a treatment option [1]. Oral use of progestin, such as megestrol acetate (MA), and medroxyprogesterone acetate (MPA) is the most commonly used method with various regimens available for treatment of EH. Nonetheless, the response rate is unsatisfactory, especially in atypical EH (approximately 70%). Moreover, oral progestins are associated with poor compliance and systemic side effects that may limit overall efficacy [2]. Therefore, to find a more effective therapeutic method, variable studies are conducted. Currently, the most notable studies of that are the treatment of EH using levonorgestrel-releasing intrauterine system (LNG-IUS) or metformin [3-13]. The LNG-IUS has already been used successfully to treat EH. Several observational studies have shown higher regression rates for LNG-IUS than for the oral progestin [4-7]. Meta-analysis of 190 observational studies including 1,001 women showed that a significantly higher regression rate was achieved with LNG-IUS than with oral progestins in treatment of atypical EH (90% vs. 69%) [2]. Recently, randomized trial comparing LNG-IUS and oral progestin as treatments for endometrial hy-perplasia proved the effectiveness of LNG-IUS [8,9]. Orbo et al. [9] showed that after 6 months, all the patients in the LNG-IUS group (53/53) including 6 atypical hyperplasia were obtained complete remission. The response rate of continuous oral progestin was 96% (46/48) and cyclic oral progestin was only 69% (36/52). In this issue of the Journal of Gynecologic Oncology, Shan et al. [10] reports a pilot study that compared the efficacy of met-formin plus MA with MA alone in treating endometrial atypical EH patients. To date, only a few case report about combined metformin with high dose progestin or oral contraceptives therapy for progestin resistant atypical EH have been reported [11,12]. Even though 75% of response rate in metformin plus oral progestin group is relatively unsatisfactory compared to reported result in treatment of atypical EH with LNG-IUS, the present study is meaningful for being the first clinical trial that has evaluated the efficacy of metformin plus oral progestin for treatment of atypical EH. Obesity, metabolic syndrome, polycystic ovarian syndrome (PCOS), insulin resistance and type II diabetes are significant risk factors of EH. Furthermore, chronic hyperinsulinemia …