LVN- IUS Versus Oral Megesterol Acetate in Treatment of Atypical Endometrial Hyperplasia

The Efficacy of Levonorgestrel Intrauterine System Versus Oral Megesterol Acetate in Treatment of Atypical Endometrial Hyperplasia. A Randomized Controlled Trial.

This randomized controlled trial is aimed to compare the efficacy between Megestrol acetate (MA) and the levonorgestrel intrauterine system (LNG-IUD) regarding the ability and duration to produce complete regression for cases with atypical endometrial hyperplasia.

Up to 25% of cases with endometrial cancer and atypical hyperplasia occur in premenopausal women. The progressively increasing trend of delay in first conception increases such patients who wish to have children.3 The recommended treatment for EH without atypia is primarily hormonal, whereas the preferred treatment for EH with atypia is hysterectomy given the significant risk for both concurrent and subsequent development of endometrial carcinoma. A dilemma results when EH with atypia is diagnosed in women who wish to retain fertility or declining doing hysterectomy due to concomitant medical morbidities. In these women, a trial of hormone therapy can be considered.4,5 In recent years, progestin therapy has been successfully used to treat selected women with endometrial cancer and atypical hyperplasia who desire to preserve fertility or having severe medical co-morbidities precluding (immediate) surgery. The most common progestin regimens include Megestrol acetate (MA) and the levonorgestrel intrauterine system (LNG-IUD).5-7

atypical endometrial hyperplasia, levonorgestrel intrauterine system, Megestrol acetate, partial regression

levonorgestrel intrauterine system (LNG-IUD) applied. Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist. Patients with persistent atypical hyperplasia in specimens done after 6 months of start of therapy will be considered resistant to therapy and hysterectomy will be done. Primary and secondary outcome data will be collected in tables with the other demographic data. All will be processed in tables for statistical analysis.

Megesterol arm will receive 160 mg daily Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist. Patients with persistent atypical hyperplasia in specimens done after 6 months of start of therapy will be considered resistant to therapy and hysterectomy will be done. Primary and secondary outcome data will be collected in tables with the other demographic data. All will be processed in tables for statistical analysis.

• Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist.

• Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist.

Inclusion Criteria: All cases with evidence of atypical endometrial hyperplasia declining doing hysterectomy Exclusion Criteria: Cases with evidence of associated endometrial cancer. Cases with simple hyperplasia without atypia. Patients failed to collect at least 2 endometrial samples during treatment course.

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Salman MC, Usubutun A, Boynukalin K, Yuce K. Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia. J Gynecol Oncol. 2010 Jun;21(2):97-101. doi: 10.3802/jgo.2010.21.2.97. Epub 2010 Jun 30.

Zhou R, Yang Y, Lu Q, Wang J, Miao Y, Wang S, Wang Z, Zhao C, Wei L. Prognostic factors of oncological and reproductive outcomes in fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin in Chinese patients. Gynecol Oncol. 2015 Dec;139(3):424-8. doi: 10.1016/j.ygyno.2015.09.078. Epub 2015 Sep 30.

Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010 Dec;203(6):547.e1-10. doi: 10.1016/j.ajog.2010.07.037.