Management of endometrial hyperplasia
- Robert L Giuntoli, II, MD
Robert L Giuntoli, II, MD
- Associate Professor, Department of Gynecology and Obstetrics
- Division of Gynecologic Oncology
- Perelman School of Medicine at the University of Pennsylvania
- Howard A Zacur, MD, PhD
Howard A Zacur, MD, PhD
- Professor of Gynecology and Obstetrics
- Johns Hopkins University School of Medicine
Endometrial hyperplasia is characterized by a proliferation of endometrial glands (the lining of the uterine cavity) that may progress to or coexist with endometrial cancer The majority of cases of endometrial hyperplasia result from chronic exposure of the endometrium to estrogen unopposed by a progestin. Obese postmenopausal women and premenopausal patients with polycystic ovarian syndrome represent two high-risk groups. The majority of women present with abnormal uterine bleeding.
Related topics can be found separately:
●Classifications, clinical manifestations, and diagnosis of endometrial hyperplasia (See "Classification and diagnosis of endometrial hyperplasia".)
●Other etiologies of abnormal uterine bleeding (See "Approach to abnormal uterine bleeding in nonpregnant reproductive-age women" and "Postmenopausal uterine bleeding".)
●Endometrial cancer (See "Endometrial carcinoma: Epidemiology and risk factors".)
- Scully RE, Bonfiglio TA, Kurman, et al. Uterine corpus. In: Histological Typing of Female Genital Tract Tumours, 2nd ed., Springer-Verlag, New York 1994. p.13.
- Mutter GL. Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? The Endometrial Collaborative Group. Gynecol Oncol 2000; 76:287.
- Eichner E, Abellera M. Endometrial hyperplasia treated by progestins. Obstet Gynecol 1971; 38:739.
- Gal D, Edman CD, Vellios F, Forney JP. Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia. Am J Obstet Gynecol 1983; 146:316.
- Gambrell RD Jr. Progestogens in estrogen-replacement therapy. Clin Obstet Gynecol 1995; 38:890.
- Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol 1989; 160:126.
- Affinito P, Di Carlo C, Di Mauro P, et al. Endometrial hyperplasia: efficacy of a new treatment with a vaginal cream containing natural micronized progesterone. Maturitas 1994; 20:191.
- Perino A, Quartararo P, Catinella E, et al. Treatment of endometrial hyperplasia with levonorgestrel releasing intrauterine devices. Acta Eur Fertil 1987; 18:137.
- Wildemeersch D, Dhont M. Treatment of nonatypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system. Am J Obstet Gynecol 2003; 188:1297.
- Vereide AB, Arnes M, Straume B, et al. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol 2003; 91:526.
- Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol 1997; 90:434.
- Dhar KK, NeedhiRajan T, Koslowski M, Woolas RP. Is levonorgestrel intrauterine system effective for treatment of early endometrial cancer? Report of four cases and review of the literature. Gynecol Oncol 2005; 97:924.
- Montz FJ, Bristow RE, Bovicelli A, et al. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol 2002; 186:651.
- Lindahl B, Willén R. Endometrial hyperplasia. Clinico-pathological considerations of a prospective randomised study after abrasio only or high-dose gestagen treatment. Results of 2 years follow-up of 292 patients. Anticancer Res 1991; 11:403.
- Reed SD, Voigt LF, Newton KM, et al. Progestin therapy of complex endometrial hyperplasia with and without atypia. Obstet Gynecol 2009; 113:655.
- Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol 2012; 125:477.
- Gallos ID, Yap J, Rajkhowa M, et al. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol 2012; 207:266.e1.
- Casper RF. Regulation of estrogen/progestogen receptors in the endometrium. Int J Fertil Menopausal Stud 1996; 41:16.
- Clark TJ, Neelakantan D, Gupta JK. The management of endometrial hyperplasia: an evaluation of current practice. Eur J Obstet Gynecol Reprod Biol 2006; 125:259.
- Abu Hashim H, Ghayaty E, El Rakhawy M. Levonorgestrel-releasing intrauterine system vs oral progestins for non-atypical endometrial hyperplasia: a systematic review and metaanalysis of randomized trials. Am J Obstet Gynecol 2015; 213:469.
- Orbo A, Vereide A, Arnes M, et al. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG 2014; 121:477.
- Gallos ID, Shehmar M, Thangaratinam S, et al. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol 2010; 203:547.e1.
- Trimble CL, Kauderer J, Zaino R, et al. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 2006; 106:812.
- Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer 1985; 56:403.
- Lacey JV Jr, Sherman ME, Rush BB, et al. Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J Clin Oncol 2010; 28:788.
- Wentz WB. Progestin therapy in endometrial hyperplasia. Gynecol Oncol 1974; 2:362.
- Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol 2012; 120:1160.
- Creasman WT, Morrow CP, Bundy BN, et al. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987; 60:2035.
- Indermaur MD, Shoup B, Tebes S, Lancaster JM. The accuracy of frozen pathology at time of hysterectomy in patients with complex atypical hyperplasia on preoperative biopsy. Am J Obstet Gynecol 2007; 196:e40.
- Attard Montalto S, Coutts M, Devaja O, et al. Accuracy of frozen section diagnosis at surgery in pre- malignant and malignant lesions of the endometrium. Eur J Gynaecol Oncol 2008; 29:435.
- Koskas M, Uzan J, Luton D, et al. Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma: systematic review and meta-analysis. Fertil Steril 2014; 101:785.
- Wheeler DT, Bristow RE, Kurman RJ. Histologic alterations in endometrial hyperplasia and well-differentiated carcinoma treated with progestins. Am J Surg Pathol 2007; 31:988.
- Scarselli G, Bargelli G, Taddei GL, et al. Levonorgestrel-releasing intrauterine system (LNG-IUS) as an effective treatment option for endometrial hyperplasia: a 15-year follow-up study. Fertil Steril 2011; 95:420.
- Wildemeersch D, Janssens D, Pylyser K, et al. Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. Maturitas 2007; 57:210.
- Ushijima K, Yahata H, Yoshikawa H, et al. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol 2007; 25:2798.
- Gunderson CC, Dutta S, Fader AN, et al. Pathologic features associated with resolution of complex atypical hyperplasia and grade 1 endometrial adenocarcinoma after progestin therapy. Gynecol Oncol 2014; 132:33.
- Gallos ID, Devey J, Ganesan R, Gupta JK. Predictive ability of estrogen receptor (ER), progesterone receptor (PR), COX-2, Mlh1, and Bcl-2 expressions for regression and relapse of endometrial hyperplasia treated with LNG-IUS: a prospective cohort study. Gynecol Oncol 2013; 130:58.
- Dolapcioglu K, Boz A, Baloglu A. The efficacy of intrauterine versus oral progestin for the treatment of endometrial hyperplasia. A prospective randomized comparative study. Clin Exp Obstet Gynecol 2013; 40:122.
- Gallos ID, Krishan P, Shehmar M, et al. LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study. Hum Reprod 2013; 28:2966.
- Mariani L, Sedati A, Giovinazzi R, et al. Postmenopausal endometrial hyperplasia: role of danazol therapy. Int J Gynaecol Obstet 1994; 44:155.
- Bulletti C, Jasonni VM, Tabanelli S, et al. Danazol reverses endometrial hyperplasia to normal endometrium. Acta Eur Fertil 1987; 18:185.
- Soh E, Sato K. Clinical effects of danazol on endometrial hyperplasia in menopausal and postmenopausal women. Cancer 1990; 66:983.
- Sedati A, Mariani L, Giovinazzi R, et al. The effectiveness of danazol therapy in postmenopausal women affected by endometrial hyperplasia. Clin Exp Obstet Gynecol 1992; 19:161.
- Grio R, Piacentino R, Marchino GL, et al. Danazol in the treatment of endometrial hyperplasia. Panminerva Med 1993; 35:231.
- Grimbizis G, Tsalikis T, Tzioufa V, et al. Regression of endometrial hyperplasia after treatment with the gonadotrophin-releasing hormone analogue triptorelin: a prospective study. Hum Reprod 1999; 14:479.
- Colacurci N, De Placido G, Galasso M, et al. The use of GnRH agonists depot for the treatment of dysfunctional uterine bleeding. Acta Eur Fertil 1991; 22:229.
- Pace S, Figliolini M, Grassi A, et al. Low-risk endometrial hyperplasia: hysteroscopy and histologic evaluation after treatment with LH-RH analogue. Clin Exp Obstet Gynecol 1994; 21:79.
- Pashov AI, Tskhay VB, Ionouchene SV. The combined GnRH-agonist and intrauterine levonorgestrel-releasing system treatment of complicated atypical hyperplasia and endometrial cancer: a pilot study. Gynecol Endocrinol 2012; 28:559.
- Agorastos T, Vaitsi V, Pantazis K, et al. Aromatase inhibitor anastrozole for treating endometrial hyperplasia in obese postmenopausal women. Eur J Obstet Gynecol Reprod Biol 2005; 118:239.
- Cianferoni L, Giannini A, Franchini M. Hysteroscopic resection of endometrial hyperplasia. J Am Assoc Gynecol Laparosc 1999; 6:151.
- OVERVIEW OF MANAGEMENT
- MECHANISM OF PROGESTIN THERAPY
- HYPERPLASIA WITHOUT ATYPIA
- Progestin therapy
- - Outcome and follow-up
- - Other options
- ATYPICAL HYPERPLASIA
- Women who have completed childbearing
- - Hysterectomy
- Bilateral salpingo-oophorectomy
- - Postmenopausal women
- - Premenopausal women
- Outcome and follow-up
- Women who wish to preserve fertility
- - Progestin therapy
- Outcome and follow-up
- Other approaches
- SUMMARY AND RECOMMENDATIONS