Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2020 Sep 6;9(9):CD012658.
doi: 10.1002/14651858.CD012658.pub2.

Levonorgestrel-releasing intrauterine system for endometrial hyperplasia

Theresa Mittermeier  1 , Charlotte Farrant  2 , Michelle R Wise  3
Affiliations
Meta-Analysis

Levonorgestrel-releasing intrauterine system for endometrial hyperplasia

Theresa Mittermeier et al. Cochrane Database Syst Rev. .

Abstract

Background: In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens.

Objectives: To evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment.

Search methods: We searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020.

Selection criteria: Randomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment.

Data collection and analysis: Two review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods.

Main results: Thirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision. LNG-IUS versus non-intrauterine progestogens Primary outcomes Regression of endometrial hyperplasia The LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence), Adverse effects associated with LNG-IUS There was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis. Secondary outcomes The LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use. LNG-IUS versus no treatment Regression of endometrial hyperplasia One study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome.

Authors' conclusions: There is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use.

Trial registration: ClinicalTrials.gov NCT01074892 NCT03241888 NCT03463252 NCT03992937.

PubMed Disclaimer

Conflict of interest statement

MW has no known conflicts of interest. CF has no known conflicts of interest. TM has no known conflicts of interest.

Figures

1
1
PRISMA flow diagram of the systematic literature search
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 LNG‐IUS versus non‐intrauterine progestogen, outcome: 1.1 Regression of EH; by length of follow‐up.
5
5
Funnel plot of comparison: 1 LNG‐IUS versus non‐intrauterine progestogen, outcome: 1.1 Regression of EH; by length of follow‐up.
1.1
1.1. Analysis
Comparison 1: LNG‐IUS versus non‐intrauterine progestogen, Outcome 1: Regression of EH; by length of follow‐up
1.2
1.2. Analysis
Comparison 1: LNG‐IUS versus non‐intrauterine progestogen, Outcome 2: Hysterectomy; histologically and non‐histologically indicated
1.3
1.3. Analysis
Comparison 1: LNG‐IUS versus non‐intrauterine progestogen, Outcome 3: Adverse effects associated with hormones
1.4
1.4. Analysis
Comparison 1: LNG‐IUS versus non‐intrauterine progestogen, Outcome 4: Withdrawal secondary to adverse effects
1.5
1.5. Analysis
Comparison 1: LNG‐IUS versus non‐intrauterine progestogen, Outcome 5: Satisfaction with treatment
2.1
2.1. Analysis
Comparison 2: LNG‐IUS versus no treatment, Outcome 1: Regression of EH
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Abdelaziz 2013 {published data only}
    1. Abdelaziz AM, Abosrie M. Levonorgestrel-releasing intrauterine system is an efficient therapeutic modality for simple endometrial hyperplasia. Journal of American Science 2013;9(11):417-24.
Abu Hashim 2013 {published data only}
    1. Abu Hashim H, Zayed A, Ghayaty E, El Rakhawy M. LNG-IUS treatment of non-atypical endometrial hyperplasia in perimenopausal women: a randomized controlled trial. Journal of Gynecologic Oncology 2013;24(2):128-34. [PMID: ] - PMC - PubMed
Behnamfar 2014 {published data only}
    1. Behnamfar F, Ghahiri A, Tavakoli M. Levonorgestrel-releasing intrauterine system (Mirena) in compare to medroxyprogesterone acetate as a therapy for endometrial hyperplasia. Journal of Research in Medical Sciences 2014;19(8):686-90. [PMID: ] - PMC - PubMed
Bian 2015 {published data only}
    1. Bian J, Shao H, Liu H, Li H, Fang L, Xing C, et al. Efficacy of the Levonorgestrel-Releasing Intrauterine System on IVF-ET Outcomes in PCOS With Simple Endometrial Hyperplasia. Reproductive Sciences (Thousand Oaks, Calif.) 2015;22(6):758-66. [PMID: ] - PubMed
Dolapcioglu 2013 {published data only}
    1. Dolapcioglu K, Boz A, Baloglu A. The efficacy of intrauterine versus oral progestin for the treatment of endometrial hyperplasia. A prospective randomized comparative study. Clinical and Experimental Obstetrics & Gynecology 2013;40(1):122-6. [PMID: ] - PubMed
El Behery 2015 {published data only}
    1. El Behery MM, Saleh HS, Ibrahiem MA, Kamal EM, Kassem GA, Mohamed Mel S. Levonorgestrel-releasing intrauterine device versus dydrogesterone for management of endometrial hyperplasia without atypia. Reproductive Sciences (Thousand Oaks, Calif.) 2015;22(3):329-34. [PMID: ] - PubMed
Ismail 2013 {published data only}
    1. Ismail MT, Fahmy DM, Elshmaa NS. Efficacy of levonorgestrel-releasing intrauterine system versus oral progestins in treatment of simple endometrial hyperplasia without atypia. Reproductive Sciences (Thousand Oaks, Calif.) 2013;20(1):45-50. [PMID: ] - PubMed
Karimi‐Zarchi 2013 {published data only}
    1. Karimi-Zarchi M, Dehghani-Firoozabadi R, Tabatabaie A, Dehghani-Firoozabadi Z, Teimoori S, Chiti Z, et al. A comparison of the effect of levonorgestrel IUD with oral medroxyprogesterone acetate on abnormal uterine bleeding with simple endometrial hyperplasia and fertility preservation. Clinical and Experimental Obstetrics & Gynecology 2013;40(3):421-4. [PMID: ] - PubMed
Orbo 2014/2016 {published data only}
    1. Orbo A, Arnes M, Vereide AB, Straume B. Relapse risk of endometrial hyperplasia after treatment with the levonorgestrel-impregnated intrauterine system or oral progestogens. BJOG 2016;123(9):1512-9. [DOI: 10.1111/1471-0528.13763] [PMID: ] - DOI - PMC - PubMed
    1. 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;121(4):477-86. [DOI: 10.1111/1471-0528.13763] [PMID: ] - DOI - PMC - PubMed
    1. Orbo A, Vereide AB, Arnes M, Pettersen I, Moe BTG, Hanssen K, et al. Levonorgestrel impregnated intrauterine device is efficient as therapy for endometrial hyperplasia: A national multi-centre randomised controlled trial. Virchows Archiv : an International Journal of Pathology 2014;465(1):S340.
Rezk 2016 {published data only}
    1. Hamza H, Rezk M, Alhalaby A, Shaheen A, Abo-Elnasr M. Comparison of levonorgestrel-releasing intrauterine system, medroxyprogesterone and norethisterone for treatment of endometrial hyperplasia without atypia. Journal of Endometriosis and Pelvic Pain Disorders 2015;7(1 Suppl):S49.
    1. Rezk M, Kandil M, Saleh S, Shaheen A. Comparison of levonorgestrel-releasing intrauterine system, medroxyprogesterone and norethisterone for treatment of endometrial hyperplasia without atypia: a randomized clinical trial. Obstetrics and Gynecology International 2016;5(4):00163.
Rizvi 2018 {published data only}
    1. Rizvi S, Ghaffar S, Haider R, Jafri A. Levonorgestrel Intrauterine System (LNG-IUS) versus medroxyprogesterone acetate for the treatment of endometrial hyperplasia: a randomized control trial. Pakistan Journal of Medical and Health Sciences 2018;12(2):675-8.
Yang 2014a {published data only}
    1. Yang X, Sun QS, He ML, Li L, Wu Q, Wang X. Efficacy of different therapies in treatment of simple endometrial hyperplasia. International Journal of Gynecological Cancer 2014;24(Suppl 4):1345. [DOI: 10.1097/01.IGC.0000457075.08973.89] - DOI
Yang 2014b {published data only}
    1. Yang X, Sun Q, Li L, He M, Wu Q. Efficacy of different therapies in treatment of endometrial hyperplasia. International Journal of Gynecological Cancer 2014;24(Suppl 4):1344.

References to studies excluded from this review

Bahamondes L 2003 {published data only}
    1. Bahamondes L, Ribeiro-Huguet P, Andrade KC, Leon-Martins O, Petta CA. Levonorgestrel-releasing intrauterine system (Mirena) as a therapy for endometrial hyperplasiaand carcinoma. Acta Obstetricia et Gynecologica Scandinavica 2003;82(6):580-2. [PMID: ] - PubMed
Gallos 2013 {published data only}
    1. Gallos ID, Krishan P, Shehmar M, Ganesan R, Gupta JK. LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study. Human Reproduction 2013;28(11):2966-71. [DOI: 10.1093/humrep/det320] [PMID: ] - DOI - PubMed
Gardener 2009 {published data only}
    1. Gardner FJ, Konje JC, Bell SC, Abrams KR, Brown LJ, Taylor DJ, Habiba M. Prevention of tamoxifen induced endometrial polyps using a levonorgestrel releasing intrauterine system long-term follow-up of a randomised control trial. Gynecologic Oncology 2009;114(3):452-6. [DOI: 10.1016/j.ygyno.2009.06.014] [PMID: 19576623 ] - DOI - PubMed
Järvelä 2005 {published data only}
    1. Järvelä IY, Santala M. Treatment of non-atypic endometrial hyperplasia using thermal balloon endometrial ablation therapy. Gynecologic and Obstetric Investigation 2005;59(4):202-6. [DOI: 10.1159/000084142] - DOI - PubMed
Kistner 1959 {published data only}
    1. Kistner RW. Histological effects of progestins on hyperplasia and carcinoma in situ of the endometrium. Cancer 1959;12(6):1106-1122. [DOI: 10.1002/1097-0142] - DOI - PubMed
La Russa 2016 {published data only}
    1. La Russa M, Biliatis I, Brockbank E, Faruki A, Lawrence A, Manchanda R, et al. Conservative treatment for fertility sparing in young women with endometrial cancer and atypical hyperplasia. Results from a on going prospective single centre study. Available at qmro.qmul.ac.uk/xmlui/handle/123456789/18943. [1048-891X]
Omelchenko 2002 {published data only}
    1. Omelchenko N, Zolotukhin M. Management of patients with climacteric syndrome and endometrial hyperplasia. In: Climacteric, 10th World Congress on Menopause. Vol. Abstract F-13-08. Berlin, Germany, 2002, June 10-14.
Orbo 2008 {published data only}
    1. Ørbo A, Arnes M, Hancke C, Vereide AB, Pettersen I, Larsen K. Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-upstudy comparing effect of LNG-IUD and oral progestins versus observation only. Gynecologic Oncology 2008;111(1):68-73. [DOI: 10.1016/j.ygyno.2008.06.014] [PMID: ] - DOI - PubMed
Ozdegirmenci 2011 {published data only}
    1. Ozdegirmenci O, Kayikcioglu F, Bozkurt U, Akgul MA, Haberal A. Comparison of the efficacy of three progestins in the treatment of simple endometrial hyperplasia without atypia. Gynecologic and Obstetric Investigation 2011;72(1):10-14. [DOI: 10.1159/000321390] [21266792] - DOI - PubMed
Randall 1997 {published data only}
    1. Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometriumin women under age 40. Obstetrics and Gynecology 1997;90(3):434-40. [PMID: ] - PubMed
Van Liedekerke 1998 {published data only}
    1. Van Liedekerke D, Gevers R, De Sutter P, Bourgain C, Amy JJ. V.2 Use of levonorgestrel intrauterine device for prevention of endometrial changes induced by tamoxifen. European Journal of Cancer 1998;34(S4):S55-S66. [DOI: 10.1016/S0959-8049(98)00116-6] - DOI
Vereide 2003 {published data only}
    1. Vereide AB, Arnes M, Straume B, Maltau JM, Ørbo A. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecologic Oncology 2003;91(3):526-33. [PMID: ] - PubMed
Wheeler 2007 {published data only}
    1. Wheeler BT, Bristow RE, Kurman MJ. Histologic alterations in endometrial hyperplasia and well-differentiated carcinoma treated with progestins. American Journal of Surgical Pathology 2007;31(7):988-98. [DOI: 10.1097/PAS.0b013e31802d68ce] [PMID: ] - DOI - PubMed
Wildemeersch 2003 {published data only}
    1. Wildemeersch D, Dhont M. Treatment of nonatypical and atypical endometrial hyperplasia with a levonorgestrel-releasingintrauterine system. American Journal of Obstetrics and Gynecology 2003;188(5):1297-8. [PMID: ] - PubMed
Yu M 2006 {published data only}
    1. Yu M, Shen K, Yang JX, Huang HF, Wu M, Pan LY, et al. [Outcome analysis of conservative treatment of well-differentiated endometrial adenocarcinomaand severe atypical hyperplasia in young women]. Zhonghua Fu Chan Ke za Zhi 2006;41(4):242-5. [PMID: ] - PubMed

References to ongoing studies

NCT03241888 {unpublished data only}
    1. NCT03241888. Megestrol Acetate Plus LNG-IUS in Young Women With Endometrial Atypical Hyperplasia [Megestrol Acetate Plus LNG-IUS to Megestrol Acetate or LNG-IUS in Young Women With Endometrial Atypical Hyperplasia]. clinicaltrials.gov/ct2/show/NCT03241888 (first received 12 July 2017).
NCT03463252 {unpublished data only}
    1. NCT03463252. Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC [Value of Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Fertility-preserving Treatment of Atypical Endometrial Hyperplasia and Early Endometrial Carcinoma]. https://clinicaltrials.gov/ct2/show/NCT03463252 (first received 4 March 2018).
NCT03992937 {unpublished data only}
    1. NCT03992937. Vaginal Micronized Progesterone Versus Levonorgestrel for Treatment of Non-atypical Endometrial Hyperplasia [Vaginal Micronized Progesterone or Levonorgestrel-releasing Intrauterine System (LNG-IUS) for Treatment of Non-atypical Endometrial Hyperplasia: A Prospective Randomized Trial]. clinicaltrials.gov/ct2/show/NCT03992937 (first received 14 June 2019).

Additional references

Abu Hashim 2015
    1. Abu Hashim H, Ghayaty E, Rakhawy ME. Levonorgestrel-releasing intrauterine system vs oral progestins for non-atypical endometrial hyperplasia: a systematic review and metaanalysis of randomised trials. American Journal of Obstetrics & Gynecology 2015;213(4):469-78. - PubMed
Anastasiadis 2000
    1. Anastasiadis PG, Skaphida PG, Koutlaki NG, Galazios GC, Tsikouras PN, Liberis VA. Descriptive epidemiology of endometrial hyperplasia in patients with abnormal uterine bleeding. European Journal of Gynaecological Oncology 2000;21(2):131-4. - PubMed
Buttini 2009
    1. Buttini MJ, Jordan SJ, Webb PM. The effect of the levonorgestrel releasing intrauterine system on endometrial hyperplasia: an Australian study and systematic review. Australian & New Zealand Journal of Obstetrics & Gynaecology 2009;49(3):316-22. [DOI: 10.1111/j.1479-828X.2009.00981.x] [PMID: ] - DOI - PubMed
Crosbie 2014
    1. Crosbie E, Morrison J. Editorial: The emerging epidemic of endometrial cancer: Time to take action. www.cochranelibrary.com/editorial/10.1002/14651858.ED000095 (accessed 29 July 2015). [DOI: 10.1002/14651858.CD000095] - DOI - PMC - PubMed
DiSaia 2018
    1. DiSaia PJ, Creasman WT, Mannel RS, McMeekin S, Mutch DG. Clinical Gynaecologic Oncology. 9th edition. Philadelphia: Elsevier, 2018. [ISBN-13: 978-0323400671]
Dominick 2015
    1. Dominick S, Hickey M, Chin J, Su IH. Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen. Cochrane Database of Systematic Reviews 2015, Issue 12. Art. No: CD007245. [DOI: 10.1002/14651858.CD007245.pub3] - DOI - PMC - PubMed
Gallos 2010
    1. Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy AMD, Gupta JK. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. American Journal of Obstetrics and Gynecology 2010;203(6):547.e1-10. - PubMed
Gallos 2013
    1. Gallos ID, Krishan P, Shehmar M, Ganesan R, Gupta JK. LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study. Human Reproduction 2013;28(11):2966-71. [DOI: 10.1093/humrep/det320] - DOI - PubMed
Giede 2008
    1. Giede KC, Yen TW, Chibbar R, Pierson RA. Significance of concurrent endometrial cancer in women with a preoperative diagnosis of atypical endometrial hyperplasia. Journal of Obstetrics and Gynaecology Canada 2008;30(10):896-901. - PMC - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT: GRADEpro Guideline Development Tool. Version accessed 1 September 2016. Hamilton (ON): McMaster University (developed by Evidence Prime, Inc.), 2015. Available from gradepro.org.
Guttinger 2007
    1. Guttinger A, Critchley H O. Endometrial effects of intrauterine levonorgestrel. Contraception 2007;75(6 Suppl):S93-8. [DOI: 10.1016/j.contraception.2007.01.015] - DOI - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
IARC
    1. International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012 v1.0. gco.iarc.fr/ (accessed on 2 May 2017).
Kokka 2010
    1. Kokka F, Brockbank E, Oram D, Gallagher C, Bryant A. Hormonal therapy in advanced or recurrent endometrial cancer (Review). Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No: CD007926. [DOI: 10.1002/14651858.CD007926.pub2] [Art. No.: CD007926] - DOI - PMC - PubMed
Kurman 1985
    1. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer 1985;56(2):403-12. - PubMed
Kurman 2011
    1. Kurman RJ, Hedrick-Ellenson L, Ronnett BM, editor(s). Blaustein's Pathology of the Female Genital Tract. 6th edition. New York: Springer, 2011.
Lacey 2010
    1. Lacey JV Jr, Sherman ME, Rush BB, Ronnett BM, Ioffe OB, Duggan MA, et al. Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. Journal of Clinical Oncology 2010;28(5):788-92. [DOI: 10.1200/JCO.2009.24.1315] - DOI - PMC - PubMed
Landrum 2012
    1. Landrum L, Zuna R, Walker JL. Endometrial hyperplasia, estrogen therapy, and the prevention of endometrial cancer. In: Di Saia P, Creasman W, editors(s). Clinical Gynecologic Oncology. 8th edition. Philadelphia: Elsevier/Saunders, 2012:121-40.
Lefebre 2011
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Lethaby 2015
    1. Lethaby A, Munawar H, Rishworth JR, Rees MC. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No: CD002126. [DOI: 10.1002/14651858.CD002126.pub3] - DOI - PubMed
Luo 2013
    1. Luo L, Luo B, Zheng Y, Zhang H, Li J, Sidell N. Levonorgestrel-releasing intrauterine system for atypical endometrial hyperplasia. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No: CD009458. [DOI: 10.1002/14651858.CD009458.pub2] - DOI - PubMed
Luo 2018
    1. Luo L, Luo B, Zheng Y, Zhang H, Li J, Sidell N. Oral and intrauterine progestogens for atypical endometrial hyperplasia. Cochrane Database of Systematic Reviews 2018, Issue 12. Art. No: CD009458. [DOI: 10.1002/14651858.CD009458.pub3] [Art. No.: CD009458] - DOI - PMC - PubMed
Morelli 2013
    1. Morelli M, Di Cello A, Venturella R, Mocciaro R, D'Alessandro P, Zullo F. Efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the prevention of the atypical endometrial hyperplasia and endometrial cancer: retrospective data from selected obese menopausal symptomatic women. Gynecological Endocrinology 2013;29(2):156-9. [DOI: 10.3109/09513590.2012.730579] - DOI - PubMed
NCT01686126
    1. NCT01686126. Improving the Treatment for Women With Early Stage Cancer of the Uterus (feMMe) [A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium]. clinicaltrials.gov/ct2/show/NCT01686126 (first received 12 Sept 2012).
NICE 2016
    1. National Institute for Health and Care Excellence. Heavy menstrual bleeding: assessment and management. Clinical guideline [CG44]. Published date: January 2007. Last updated: August 2016. www.nice.org.uk/guidance/cg44 (accessed 30 July 2015).
Pal 2018
    1. Pal N, Broaddus RR, Urbauer DL, Balakrishnan N, Milbourne A, Schmeler KM, et al. Treatment of low-risk endometrial cancer and complex atypical hyperplasia with the levonorgestrel-releasing intrauterine device. Obstetrics and Gynecology 2018;131(1):109-16. [DOI: 10.1097/AOG.0000000000002390] [PMID: ] - DOI - PMC - PubMed
Pfizer 2016
    1. Pfizer New Zealand Ltd. Provera Medroxyprogesterone acetate data sheet October 2016. www.medsafe.govt.nz/profs/Datasheet/p/Proveratab.pdf (accessed 28 April 2017).
RCOG 2016
    1. Gallos ID, Alazzam M, Clark TJ, Faraj R, Rosenthal AN, Smith PP, et al. Management of Endometrial Hyperplasia. Green-top Guideline No. 67. www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/g... (accessed 30 July 2015).
Review Manager 2014 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Sangkomkamhang 2013
    1. Sangkomkamhang US, Lumbiganon P, Laopaiboon M, Mol BWJ. Progestogens or progestogen-releasing intrauterine systems for uterine fibroids. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No: CD008994. [DOI: 10.1002/14651858.CD008994.pub2] - DOI - PubMed
Scully 1994
    1. Scully RE, Bonfiglio TA, Kurman RJ, Silverberg SG, Wilkinson EJ. Histological typing of female genital tract tumours. In: Sobin LH, editors(s). International Histological Classification of Tumours. 2nd edition. Berlin, Heidelberg: Springer-Verlag, 1994. [DOI: 10.1007/978-3-642-85014-1] - DOI
Singh 2013
    1. Singh S, Best C, Dunn S, Leyland N, Wolfman WL, Clinical Practice - Gynaecology Committee, et al. SOGC Clinical Practice Guideline: abnormal uterine bleeding in pre-menopausal women. Journal of Obstetrics and Gynaecology Canada 2013;35(5 Suppl 1):S1-S28. - PubMed
Trimble 2006
    1. Trimble CL, Kauderer J, Zaino R, Silverberg S, Lim PC, Burke JJ 2nd, et al. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 2006;106(4):812-9. - PubMed
Vilos 2011
    1. Vilos GA, Marks J, Tureanu V, Abu-Rafea B, Vilos AG. The levonorgestrel intrauterine system Is an effective treatment in selected obese women with abnormal uterine bleeding. Journal of Minimally Invasive Gynecology 2011;18(1):75-80. [DOI: 10.1016/j.jmig.2010.09.013] - DOI - PubMed
Wise 2016
    1. Wise M, Jordan V, Lagas A, Showell M, Wong N, Lensen S, et al. Obesity and endometrial hyperplasia and cancer in premenopausal women: a systematic review. American Journal of Obstetrics and Gynecology 2016;214(6):689.e1-e17. [DOI: 10.1016/j.ajog.2016.01.175] - DOI - PubMed
Yuk 2017
    1. Yuk JS, Song JY, Lee JH, Park WI, Ahn HS, Kim HJ. Levonorgestrel-releasing intrauterine systems versus oral cyclic medroxyprogesterone acetate in endometrial hyperplasia therapy: a meta-analysis. Annals of Surgical Oncology 2017 May;25(5):1322-9. [DOI: 10.1245/s10434-016-5699-9] [PMID: ] - DOI - PubMed
Zaino 2014
    1. Zaino R, Carinelli SG, Ellenson LH. Tumours of the uterine corpus: epithelial tumours and precursors. In: Kurman RJ, Carcangiu ML, Herrington CS, Young RH, editors(s). WHO Classification of Tumours of Female Reproductive Organs. 4th edition. Lyon: WHO Press, 2014:125-6.

MeSH terms

Associated data

LinkOut - more resources