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

  • Gynecologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Disclosure

There are no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, College of Medicine, Gyeongsang National University, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea

    Jin-Sung Yuk MD, PhD & Jung Hun Lee MD, PhD

  2. Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Jae Yen Song MD, PhD

  3. Department of Obstetrics and Gynecology, College of Medicine, Hangang Sacred Heart Hospital, Hallym University, Seoul, Republic of Korea

    Won I. Park MD, PhD

  4. Department of Preventive Medicine, Institute for Evidence-Based Medicine, College of Medicine, Korea University, Seoul, Republic of Korea

    Hyeong Sik Ahn MD, PhD & Hyun Jung Kim MPH, PhD

Authors
  1. Jin-Sung Yuk MD, PhD
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  2. Jae Yen Song MD, PhD
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  3. Jung Hun Lee MD, PhD
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  4. Won I. Park MD, PhD
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  5. Hyeong Sik Ahn MD, PhD
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  6. Hyun Jung Kim MPH, PhD
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Corresponding author

Correspondence to Hyun Jung Kim MPH, PhD.

Electronic supplementary material

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Supplemental Fig. 1

LNG-IUS versus MPA: Regression rate of subgroup analysis according to follow-up period in non-obese group. (1) 3-month follow-up (2) 6-month follow-up. LNG-IUS, levonorgestrel-releasing intrauterine system; MPA, medroxyprogesterone acetate. Supplementary material 1 (TIFF 1505 kb)

Appendix 1

Appendix 1

MEDLINE search strategy

  1. 1.

    “endometrial hyperplasia”[tiab] OR “endometrial hyperplasias”[tiab] 2582

  2. 2.

    “Endometrial Hyperplasia”[Mesh] 3002

  3. 3.

    1 OR 2 4295

  4. 4.

    “Levonorgestrel-releasing”[tiab] OR “Mirena”[tiab] OR “LNG-IUS”[tiab] OR “LNG-IUD”[tiab] OR “Levonorgestrel”[tiab] OR “D-Norgestrel”[tiab] OR “D Norgestrel”[tiab] OR “l-Norgestrel”[tiab] OR “l Norgestrel”[tiab] 4006

  5. 5.

    (“Intrauterine Devices, Medicated”[Mesh:NoExp]) OR “Levonorgestrel”[Mesh] 4037

  6. 6.

    4 OR 5 5589

  7. 7.

    medroxyprogesterone[tiab] OR Methylhydroxyprogesterone[tiab] OR MPA[tiab] OR Progestins[tiab] OR progestin[tiab] OR Progestagens[tiab] OR Progestagen[tiab] OR Progestagenic[tiab] OR Progestogen[tiab] OR Progestogens[tiab] 38642

  8. 8.

    (“Medroxyprogesterone”[Mesh]) OR “Progestins”[Mesh] 14759

  9. 9.

    7 OR 8 45146

  10. 10.

    6 OR 9 49009

  11. 11.

    3 AND 10 708

  12. 12.

    11 AND ((“randomized controlled trial”[Publication Type] OR “controlled clinical trial”[Publication Type] OR randomized[tiab] OR placebo[tiab] OR “clinical trials as topic”[Mesh:noexp] OR randomly[tiab] OR trial[ti])) NOT ((animals[Mesh] NOT (humans[Mesh] AND animals[Mesh]))) 152

EMBASE search strategy

  1. 1.

    ‘endometrial hyperplasia’:ab,ti OR ‘endometrial Hyperplasias’:ab,ti 3377

  2. 2.

    ‘endometrium hyperplasia’/exp 6154

  3. 3.

    1 OR 2 6841

  4. 4.

    ‘Levonorgestrel-releasing’:ab,ti OR ‘Mirena’:ab,ti OR ‘LNG-IUS’:ab,ti OR ‘LNG-IUD’:ab,ti OR ‘Levonorgestrel’:ab,ti OR ‘D-Norgestrel’:ab,ti OR ‘D Norgestrel’:ab,ti OR ‘l-Norgestrel’:ab,ti OR ‘l Norgestrel’:ab,ti 4904

  5. 5.

    ‘levonorgestrel releasing intrauterine system’/exp OR ‘intrauterine contraceptive device’/de OR ‘levonorgestrel’/exp 21879

  6. 6.

    4 OR 5 22956

  7. 7.

    medroxyprogesterone:ab,ti OR Methylhydroxyprogesterone:ab,ti OR MPA:ab,ti OR Progestins:ab,ti OR progestin:ab,ti OR Progestagens:ab,ti OR Progestagen:ab,ti OR Progestagenic:ab,ti OR Progestogen:ab,ti OR Progestogens:ab,ti 43236

  8. 8.

    ‘medroxyprogesterone’/exp OR ‘gestagen’/de 27387

  9. 9.

    7 OR 8 60226

  10. 10.

    6 OR 9 78647

  11. 11.

    3 AND 10 1535

  12. 12.

    11 AND ‘crossover procedure’/exp OR ‘double blind procedure’/exp OR ‘randomized controlled trial’/exp OR ‘single blind procedure’/exp OR random* OR factorial* OR crossover* OR ‘cross over’ OR ‘cross-over’ OR placebo* OR (doubl* AND blind*) OR (singl* AND blind*) OR assign* OR allocat* OR volunteer* 383

  13. 13.

    12 NOT (‘animal experiment’/de OR ‘nonhuman’/de OR ‘observational study’/de) 314

  14. 14.

    13 NOT (‘article in press’/it OR ‘editorial’/it OR ‘letter’/it OR ‘note’/it OR ‘short survey’/it) 285

COCHRANE search strategy

  1. 1.

    “endometrial hyperplasia” or “endometrial Hyperplasias”:ti,ab,kw 247

  2. 2.

    MeSH descriptor: [Endometrial Hyperplasia] explode all trees 112

  3. 3.

    1 OR 2 247

  4. 4.

    “Levonorgestrel-releasing” or “Mirena” or “LNG-IUS” or “LNG-IUD” or “Levonorgestrel” or “D-Norgestrel” or “D Norgestrel” or “l-Norgestrel” or “l Norgestrel”:ti,ab,kw 1089

  5. 5.

    Intrauterine Devices, Medicated:ti,ab,kw 198

  6. 6.

    MeSH descriptor: [Levonorgestrel] explode all trees 633

  7. 7.

    4-6/OR 1135

  8. 8.

    medroxyprogesterone or Methylhydroxyprogesterone or MPA or Progestins or progestin or Progestagens or Progestagen or Progestagenic or Progestogen or Progestogens:ti,ab,kw 3853

  9. 9.

    MeSH descriptor: [Medroxyprogesterone] explode all trees 1045

  10. 10.

    MeSH descriptor: [Progestins] explode all trees 399

  11. 11.

    8-10/OR 3853

  12. 12.

    7 OR 11 4717

  13. 13.

    3 AND 12 115

  14. 14.

    13/Trials 105

KOREAMED search strategy

  1. 1.

    “endometrial hyperplasia”[ALL] OR “endometrial Hyperplasias”[ALL] 94

  2. 2.

    “Levonorgestrel-releasing”[ALL] OR “Mirena”[ALL] OR “LNG-IUS”[ALL] OR “LNG-IUD”[ALL] OR “Levonorgestrel”[ALL] OR “D-Norgestrel”[ALL] OR “D Norgestrel”[ALL] OR “l-Norgestrel”[ALL] OR “l Norgestrel”[ALL] 19

  3. 3.

    medroxyprogesterone[ALL] OR Methylhydroxyprogesterone[ALL] OR MPA[ALL] OR Progestins[ALL] OR progestin[ALL] OR Progestagens[ALL] OR Progestagen[ALL] OR Progestagenic[ALL] OR Progestogen[ALL] OR Progestogens[ALL] 294

  4. 4.

    1-3/AND 1

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Yuk, JS., Song, J.Y., Lee, J.H. et al. Levonorgestrel-Releasing Intrauterine Systems Versus Oral Cyclic Medroxyprogesterone Acetate in Endometrial Hyperplasia Therapy: A Meta-Analysis. Ann Surg Oncol 24, 1322–1329 (2017). https://doi.org/10.1245/s10434-016-5699-9

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  • DOI: https://doi.org/10.1245/s10434-016-5699-9

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