Medicine by the Numbers

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Levonorgestrel-Releasing Intrauterine System for Regression of Endometrial Hyperplasia


Am Fam Physician. 2021 Jul ;104(1):26-27.


Details for This Review

Study Population: Patients 22 to 75 years of age with histologic evidence of endometrial hyperplasia

Efficacy End Points: Regression of endometrial hyperplasia when treated with the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena) for six months or less and for 12 months (regression was defined as biopsy showing return to normal or a change from atypical hyperplasia to endometrial hyperplasia without atypia); avoidance of hysterectomy for a malignant or nonmalignant reason

Harm End Points: Requested removal of the LNG-IUS because of adverse effects (e.g., spotting, nausea, weight gain)

Narrative: Endometrial hyperplasia is the excessive production of cells in the endometrium caused by unopposed estrogen states, such as obesity, anovulatory bleeding, and hormone therapy. Endometrial hyperplasia is the precursor to endometrial cancer, the sixth most common cancer worldwide.1 Progesterone therapy leads to regression of endometrial hyperplasia and prevention of endometrial cancer. The most common regimen is six months of intramuscular or high-dose oral progesterone, either of which can cause significant adverse effects. Surgery is another option, but its use may be limited for those wishing to maintain fertility.1

This Cochrane review of 13 randomized controlled trials (RCTs) included 3,174 patients from Egypt, Iran, China, Turkey, Kuwait, Pakistan, and Norway. Treatment of endometrial hyperplasia with the LNG-IUS (1,657 patients) was compared with systemic progesterone (1,327 patients) or no treatment (190 patients).1 Systemic progesterone was administered orally in 12 studies and intramuscularly in one study. Endometrial hyperplasia was diagnosed through endometrial sampling (endometrial biopsy or suction curettage) with histologic evaluation. Twelve trials included endometrial hyperplasia without atypia, and one study included endometrial hyperplasia with atypia. Sampling with histologic examination was performed again at the end of the treatment period to determine treatment effectiveness.

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1 in 7 patients had regression of endometrial hyperplasia after treatment with the LNG-IUS for 6 months or less (NNT = 7; moderate-certainty evidence; 1,108 patients)

Insufficient evidence

1 in 4 patients had regression of endometrial hyperplasia after treatment with the LNG-IUS for 12 months (NNT = 4; low-certainty evidence; n = 138)

1 in 7 patients avoided hysterectomy after treatment with the LNG-IUS (NNT = 7; low-certainty evidence; n = 452)

LNG-IUS = levonorgestrel-releasing intrauterine system; NNT = number needed to treat.



1 in 7 patients had regression of endometrial hyperplasia after treatment with the LNG-IUS for 6 months or

Author disclosure: No relevant financial affiliations.

The views expressed within this publication represent those of the authors and do not reflect the official position of U.S. Air Force, Uniformed Services University of the Health Sciences, the U.S. government, or the Department of Defense at large.

Copyright © 2021 MD Aware, LLC ( Used with permission.

This series is coordinated by Christopher W. Bunt, MD, AFP assistant medical editor, and the NNT Group.

A collection of Medicine by the Numbers published in AFP is available at


1. Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020;(9):CD012658.

2. Luukkainen T, Toivonen J. Levonorgestrel-releasing IUD as a method of contraception with therapeutic properties. Contraception. 1995;52(5):269–276.

3. American College of Obstetricians and Gynecologists. Endometrial intraepithelial neoplasia. Committee opinion number 631. May 2015. Accessed March 27, 2021.



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