A Study Comparing Mirena and Systemic Progestin for Endometrial Hyperplasia

Summary

Randomized controlled multi-center study with three arms including 200 patients with low risk endometrial hyperplasia. After confirmed diagnosis the patients will receive one of the following treatments: 1. Provera (Medroxyprogesterone (MPA)/progestin) 10 mg per oral treatment for 6 months 10 day each cycle, 2. MPA 10 mg continuously for 6 months, 3. Mirena (Levonorgestrel) impregnated IUD for 6 months.

Timeline

Start

2005-05

Primary completion

2013-12

Completion

2013-12

Publications

• Background Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer. 1985 Jul 15;56(2):403-12. doi: 10.1002/1097-0142(19850715)56:23.0.co;2-x.
• Background Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol. 1989 Jan;160(1):126-31. doi: 10.1016/0002-9378(89)90103-8.
• Background Orbo A, Baak JP, Kleivan I, Lysne S, Prytz PS, Broeckaert MA, Slappendel A, Tichelaar HJ. Computerised morphometrical analysis in endometrial hyperplasia for the prediction of cancer development. A long-term retrospective study from northern Norway. J Clin Pathol. 2000 Sep;53(9):697-703. doi: 10.1136/jcp.53.9.697.
• Background Vereide AB, Arnes M, Straume B, Maltau JM, Orbo A. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2003 Dec;91(3):526-33. doi: 10.1016/j.ygyno.2003.07.002.
• Background Nilsson CG, Haukkamaa M, Vierola H, Luukkainen T. Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD. Clin Endocrinol (Oxf). 1982 Dec;17(6):529-36. doi: 10.1111/j.1365-2265.1982.tb01625.x.
• Background Scarselli G, Tantini C, Colafranceschi M, Taddei GL, Bargelli G, Venturini N, Branconi F. Levo-norgestrel-nova-T and precancerous lesions of the endometrium. Eur J Gynaecol Oncol. 1988;9(4):284-6.
• Background Orbo A, Arnes M, Hancke C, Vereide AB, Pettersen I, Larsen K. Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-up study comparing effect of LNG-IUD and oral progestins versus observation only. Gynecol Oncol. 2008 Oct;111(1):68-73. doi: 10.1016/j.ygyno.2008.06.014. Epub 2008 Aug 6.
• Background Baak JP, Nauta JJ, Wisse-Brekelmans EC, Bezemer PD. Architectural and nuclear morphometrical features together are more important prognosticators in endometrial hyperplasias than nuclear morphometrical features alone. J Pathol. 1988 Apr;154(4):335-41. doi: 10.1002/path.1711540409.
• Background Perino A, Quartararo P, Catinella E, Genova G, Cittadini E. Treatment of endometrial hyperplasia with levonorgestrel releasing intrauterine devices. Acta Eur Fertil. 1987 Mar-Apr;18(2):137-40.
• Background Vereide AB, Kaino T, Sager G, Orbo A; Scottish Gynaecological Clinical Trials Group. Bcl-2, BAX, and apoptosis in endometrial hyperplasia after high dose gestagen therapy: a comparison of responses in patients treated with intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2005 Jun;97(3):740-50. doi: 10.1016/j.ygyno.2005.02.030.
• Background Vereide AB, Kaino T, Sager G, Arnes M, Orbo A. Effect of levonorgestrel IUD and oral medroxyprogesterone acetate on glandular and stromal progesterone receptors (PRA and PRB), and estrogen receptors (ER-alpha and ER-beta) in human endometrial hyperplasia. Gynecol Oncol. 2006 May;101(2):214-23. doi: 10.1016/j.ygyno.2005.10.030. Epub 2005 Dec 1.
• Background Moe BT, Vereide AB, Orbo A, Jaeger R, Sager G. Levonorgestrel, medroxyprogesterone and progesterone cause a concentration-dependent reduction in endometrial cancer (Ishikawa) cell density, and high concentrations of progesterone and mifepristone act in synergy. Anticancer Res. 2009 Apr;29(4):1047-52.
• Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020 Sep 6;9(9):CD012658. doi: 10.1002/14651858.CD012658.pub2.
• Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.

Drugs

Indications