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Erschienen in: Annals of Surgical Oncology 5/2017

28.11.2016 | Gynecologic Oncology

Levonorgestrel-Releasing Intrauterine Systems Versus Oral Cyclic Medroxyprogesterone Acetate in Endometrial Hyperplasia Therapy: A Meta-Analysis

verfasst von: Jin-Sung Yuk, MD, PhD, Jae Yen Song, MD, PhD, Jung Hun Lee, MD, PhD, Won I. Park, MD, PhD, Hyeong Sik Ahn, MD, PhD, Hyun Jung Kim, MPH, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 5/2017

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Abstract

Background

This study aimed to compare the levonorgestrel-releasing intrauterine system (LNG-IUS) with oral cyclic medroxyprogesterone acetate (MPA) in endometrial hyperplasia therapy using randomized controlled trials (RCTs).

Methods

The study searched MEDLINE, EMBASE, CENTRAL, and other databases. All regression outcomes were calculated for dichotomous outcomes in terms of relative risk (RR) and 95% confidence intervals (CIs) using a Mantel–Haenszel random effects model.

Results

The search found 543 articles but selected 342 articles after the removal of duplicates. A meta-analysis found five RCTs (377 patients). The study did not analyze RR for total outcome because of high heterogeneity (I 2 = 87%). In a subgroup analysis of studies with non-obese women, the LNG-IUS treatment appeared to have a higher regression rate than oral MPA (RR 1.41; 95% CI 1.23–1.62; 4 trials, 265 patients; I 2 = 0%). In a subgroup analysis of studies with obese women, LNG-IUS appeared to have a regression rate similar to that of oral MPA (RR 1.03; 95% CI 0.94–1.13; 1 trial, 60 patients). In a subgroup analysis according to histology in the non-obese group, the LNG-IUS treatment appeared to have a higher regression rate than oral cyclic MPA in a meta-analysis of women with non-atypical endometrial hyperplasia (RR 1.36; 95% CI 1.07–1.73; 2 trials, 92 patients; I 2 = 6%) and mixed endometrial hyperplasia (atypical and non-atypical) (RR 1.44; 95% CI 1.21–1.71; 2 trials, 173 patients; I 2 = 0%).

Conclusions

The LNG-IUS treatment has a higher regression rate than cyclic MPA in non-atypical endometrial hyperplasia and mixed endometrial hyperplasia therapy for non-obese women but has a similar regression rate, albeit limited, for obese women.
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Literatur
1.
Zurück zum Zitat Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti KM. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012;19:562–71.CrossRefPubMed Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti KM. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012;19:562–71.CrossRefPubMed
2.
Zurück zum Zitat Reed SD, Newton KM, Clinton WL, Epplein M, Garcia R, Allison K, et al. Incidence of endometrial hyperplasia. Am J Obstet Gynecol. 2009;200:678.e1–6. Reed SD, Newton KM, Clinton WL, Epplein M, Garcia R, Allison K, et al. Incidence of endometrial hyperplasia. Am J Obstet Gynecol. 2009;200:678.e1–6.
3.
4.
Zurück zum Zitat Carlson MJ, Thiel KW, Yang S, Leslie KK. Catch it before it kills: progesterone, obesity, and the prevention of endometrial cancer. Discov Med. 2012;14:215–22.PubMedPubMedCentral Carlson MJ, Thiel KW, Yang S, Leslie KK. Catch it before it kills: progesterone, obesity, and the prevention of endometrial cancer. Discov Med. 2012;14:215–22.PubMedPubMedCentral
5.
Zurück zum Zitat Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia: a long-term study of “untreated” hyperplasia in 170 patients. Cancer. 1985;56:403–12.CrossRefPubMed Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia: a long-term study of “untreated” hyperplasia in 170 patients. Cancer. 1985;56:403–12.CrossRefPubMed
6.
Zurück zum Zitat Trimble CL, Method M, Leitao M, Lu K, Loffe O, Hampton M, et al. Management of endometrial precancers. Obstet Gynecol. 2012;120:1160–75.PubMedPubMedCentral Trimble CL, Method M, Leitao M, Lu K, Loffe O, Hampton M, et al. Management of endometrial precancers. Obstet Gynecol. 2012;120:1160–75.PubMedPubMedCentral
7.
Zurück zum Zitat MMS JSBM. Berek and Novak’s gynecology. Fifteenth, North American Edition ed. LWW, Philadelphia, 2011. MMS JSBM. Berek and Novak’s gynecology. Fifteenth, North American Edition ed. LWW, Philadelphia, 2011.
8.
Zurück zum Zitat Wildemeersch D, Dhont M. Treatment of nonatypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system. Am J Obstet Gynecol. 2003;188:1297–8.CrossRefPubMed Wildemeersch D, Dhont M. Treatment of nonatypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system. Am J Obstet Gynecol. 2003;188:1297–8.CrossRefPubMed
9.
Zurück zum Zitat 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;203:547.e1–10. 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;203:547.e1–10.
10.
Zurück zum Zitat Abu Hashim H, Ghayaty E, Rakhawy ME. Levonorgestrel-releasing intrauterine system versus oral progestins for non-atypical endometrial hyperplasia: a systematic review and meta-analysis of randomized trials. Am J Obstet Gynecol. 2015;213:469–78.CrossRefPubMed Abu Hashim H, Ghayaty E, Rakhawy ME. Levonorgestrel-releasing intrauterine system versus oral progestins for non-atypical endometrial hyperplasia: a systematic review and meta-analysis of randomized trials. Am J Obstet Gynecol. 2015;213:469–78.CrossRefPubMed
11.
Zurück zum Zitat Ewies AAA, Alfhaily F. Use of levonorgestrel-releasing intrauterine system in the prevention and treatment of endometrial hyperplasia. Obstet Gynecol Surv. 2012;67:726–33.CrossRefPubMed Ewies AAA, Alfhaily F. Use of levonorgestrel-releasing intrauterine system in the prevention and treatment of endometrial hyperplasia. Obstet Gynecol Surv. 2012;67:726–33.CrossRefPubMed
12.
Zurück zum Zitat Shuster JJ. Review: cochrane handbook for systematic reviews for interventions, version 5.1.0, published 3/2011. In: Higgins JPT, Green S, editors. Res Synth Methods. 2011;2:126–30. Shuster JJ. Review: cochrane handbook for systematic reviews for interventions, version 5.1.0, published 3/2011. In: Higgins JPT, Green S, editors. Res Synth Methods. 2011;2:126–30.
13.
Zurück zum Zitat Stewart LA, Clarke M, Rovers M, Riley RD, Simmonds M, Stewart G, et al. Preferred reporting items for systematic review and meta-analyses of individual participant data: the PRISMA-IPD Statement. JAMA. 2015;313:1657–65.CrossRefPubMed Stewart LA, Clarke M, Rovers M, Riley RD, Simmonds M, Stewart G, et al. Preferred reporting items for systematic review and meta-analyses of individual participant data: the PRISMA-IPD Statement. JAMA. 2015;313:1657–65.CrossRefPubMed
15.
Zurück zum Zitat 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;40:122–6.PubMed 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;40:122–6.PubMed
16.
Zurück zum Zitat Ismail MT, Fahmy DM, Elshmaa NS. Efficacy of levonorgestrel-releasing intrauterine system versus oral progestins in treatment of simple endometrial hyperplasia without atypia. Reprod Sci Thousand Oaks Calif. 2013;20:45–50.CrossRef Ismail MT, Fahmy DM, Elshmaa NS. Efficacy of levonorgestrel-releasing intrauterine system versus oral progestins in treatment of simple endometrial hyperplasia without atypia. Reprod Sci Thousand Oaks Calif. 2013;20:45–50.CrossRef
17.
Zurück zum Zitat 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. Clin Exp Obstet Gynecol. 2013;40:421–4.PubMed 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. Clin Exp Obstet Gynecol. 2013;40:421–4.PubMed
18.
Zurück zum Zitat Behnamfar F, Ghahiri A, Tavakoli M. Levonorgestrel-releasing intrauterine system (Mirena) in compare to medroxyprogesterone acetate as a therapy for endometrial hyperplasia. J Res Med Sci Off J Isfahan Univ Med Sci. 2014;19:686–90. Behnamfar F, Ghahiri A, Tavakoli M. Levonorgestrel-releasing intrauterine system (Mirena) in compare to medroxyprogesterone acetate as a therapy for endometrial hyperplasia. J Res Med Sci Off J Isfahan Univ Med Sci. 2014;19:686–90.
19.
Zurück zum Zitat 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 Int J Obstet Gynaecol. 2014;121:477–86.CrossRef 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 Int J Obstet Gynaecol. 2014;121:477–86.CrossRef
20.
Zurück zum Zitat Yang X, Sun QS, He ML, Li L, Wu Q, Wang XZ. Efficacy of different therapies in treatment of simple endometrial hyperplasia. Int J Gynecol Cancer. 2014;24:1344. Yang X, Sun QS, He ML, Li L, Wu Q, Wang XZ. Efficacy of different therapies in treatment of simple endometrial hyperplasia. Int J Gynecol Cancer. 2014;24:1344.
21.
Zurück zum Zitat Pronin SM, Novikova OV, Andreeva JY, Novikova EG. Fertility-sparing treatment of early endometrial cancer and complex atypical hyperplasia in young women of childbearing potential. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2015;25:1010–4.CrossRef Pronin SM, Novikova OV, Andreeva JY, Novikova EG. Fertility-sparing treatment of early endometrial cancer and complex atypical hyperplasia in young women of childbearing potential. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2015;25:1010–4.CrossRef
22.
Zurück zum Zitat Westin SN, Sun CCL, Broaddus R, et al. Challenging the paradigm of progesterone-only therapy for early endometrial cancer: results of a prospective trial of the levonorgestrel intrauterine system. Gynecol Oncol. 2016;141:18–9.CrossRef Westin SN, Sun CCL, Broaddus R, et al. Challenging the paradigm of progesterone-only therapy for early endometrial cancer: results of a prospective trial of the levonorgestrel intrauterine system. Gynecol Oncol. 2016;141:18–9.CrossRef
23.
Zurück zum Zitat Kobayashi K, Mimura N, Fujii H, et al. Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate. Clin Cancer Res Off J Am Assoc Cancer Res. 2000;6:3297–303. Kobayashi K, Mimura N, Fujii H, et al. Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate. Clin Cancer Res Off J Am Assoc Cancer Res. 2000;6:3297–303.
24.
Zurück zum Zitat Nilsson CG, Haukkamaa M, Vierola H, Luukkainen T. Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD. Clin Endocrinol Oxford. 1982;17:529–36.CrossRef Nilsson CG, Haukkamaa M, Vierola H, Luukkainen T. Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD. Clin Endocrinol Oxford. 1982;17:529–36.CrossRef
25.
Zurück zum Zitat Lee BS, Ling X, Asif S, et al. Therapy of heavy menstrual bleeding in Korea: subanalysis and results from a multinational clinical trial in the Asian region investigating the levonorgestrel-releasing intrauterine system versus conventional therapy. Obstet Gynecol Sci. 2015;58:162–70.CrossRefPubMedPubMedCentral Lee BS, Ling X, Asif S, et al. Therapy of heavy menstrual bleeding in Korea: subanalysis and results from a multinational clinical trial in the Asian region investigating the levonorgestrel-releasing intrauterine system versus conventional therapy. Obstet Gynecol Sci. 2015;58:162–70.CrossRefPubMedPubMedCentral
Metadaten
Titel
Levonorgestrel-Releasing Intrauterine Systems Versus Oral Cyclic Medroxyprogesterone Acetate in Endometrial Hyperplasia Therapy: A Meta-Analysis
verfasst von
Jin-Sung Yuk, MD, PhD
Jae Yen Song, MD, PhD
Jung Hun Lee, MD, PhD
Won I. Park, MD, PhD
Hyeong Sik Ahn, MD, PhD
Hyun Jung Kim, MPH, PhD
Publikationsdatum
28.11.2016
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 5/2017
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5699-9

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