Search tips
Search criteria 


Logo of jgoJournal of Gynecologic OncologyAims and ScopeInformations for Authorse-SubmissionThis Article
J Gynecol Oncol. 2010 June; 21(2): 102–105.
Published online 2010 June 30. doi:  10.3802/jgo.2010.21.2.102
PMCID: PMC2895708

The effectiveness of levonorgestrel releasing intrauterine system in the treatment of endometrial hyperplasia in Korean women



Levonorgestrel releasing intrauterine system (LNG-IUS) has been shown to treat patients with non-atypical & atypical endometrial hyperplasia (EH) successfully in many western studies. Our purpose was to examine the effectiveness of LNG-IUS in the treatment of Korean women with EH.


We conducted a prospective observational study of 12 women diagnosed with EH and treated with LNG-IUS insertion between February 2007 and August 2009 at the Department of Gynecology of Gangnam CHA Hospital, CHA University School of Medicine. Baseline endometrial biopsies were done before insertion of LNG-IUS, and outpatient follow-up endometrial biopsies were undertaken at 3-month intervals after insertion of LNG-IUS. We investigated the regression rate and the time to regression.


Four patients had simple hyperplasia without atypia, 7 patients complex hyperplasia without atypia, and just 1 patient complex atypical hyperplasia. Complete regression of EH was achieved in all cases (100%, 12/12), with the significant proportion (66%, 8/12) achieving it within 3 months. The mean duration to regression was 4.5 months. All cases had regression within 9 months. In the case of complex atypical hyperplasia, the regression was attained at the 9th month after insertion of LNG-IUS. The mean follow-up duration was 12 months (range, 3 to 27 months). As long as LNG-IUS was maintained, the EH did not recur.


LNG-IUS appears to be as highly effective in treating Korean women with EH.

Keywords: Endometrial hyperplasia, LNG-IUS, Korean women, Progestin, Mirena


Endometrial hyperplasia (EH) is defined as a morphologic and biologic alteration of endometrium as a result of protracted estrogen stimulation in the absence of progestin influence. EH has been regarded as a premalignant lesion. Cytologic atypia is the most important factor for progression to carcinoma.1-3 About 1-3% of hyperplasia without atypia were observed to progress to carcinoma over 10 years' follow-up. On the contrary, 8-29% of atypical hyperplasia progress to carcinoma over 4 years' follow up.1

The goals of treating women with EH include not only relieving the symptoms of abnormal uterine bleeding but also preventing progression to carcinoma.4,5 From the viewpoint of oncogenic potential of EH, hysterectomy has been generally recommended for the treatment of atypical EH except when the women have strong desire for fertility or have serious surgical risk factors.4,6,7 Oral progesterone has been used to treat women with EH who want to the conserve uterus. But some systemic side effects and poor compliance have been reported to be associated with oral progesterone. Compared with oral progesterone, LNG-IUS has been reported to have less systemic side effects and higher efficacy for the treatment of EH in many studies targeting the women of western countries.8-12

To our knowledge, there has been no study reporting the effectiveness of LNG-IUS in treating Korean women with EH. Considering the variation of treatment responses among the variable ethnicity, we investigated the effectiveness of LNG-IUS in treating non-atypical and atypical EH in Korean women.


Twelve patients participating in this study had presented with abnormal uterine bleeding to the Gynecologic Department, Gangnam CHA Hospital. All women were diagnosed with EH and treated with LNG-IUS (Mirena®) from February 2007 to August 2009.

For diagnosis and assessment of treatment responses, we performed transvaginal sonography (TVS) and outpatient endometrial biopsy. The methods of endometrial biopsy were endometrial sampling with a catheter (8 women, 66.6%), D&C (3 women, 25%), and hysterscopic biopsy (1 woman, 8.3%). One patient who had been suspected of an endometrial polyp on TVS was eventually diagnosed with EH after hysteroscopic polypectomy, and she entered the study.

EH was divided into 4 categories by the Kurman criteria: simple hyperplasia without atypia, complex hyperplasia without atypia, simple hyperplasia with atypia, and complex hyperplasia with atypia.13 In assessing the histological treatment response, complete regression was defined as endometrial atrophy, pseudodecidualization of stroma without evidence of hyperplasia. Complete regression could be accompanied by secretory change of glandular tissue or metaplasia.4,14

We collected the demographic data including age and risk factors for EH, such as parity, weight, height, diabetes, and hypertension. The method of initial diagnosis and the type of EH were recorded. During follow-up at scheduled intervals, we conducted TVS and endometrial biopsy using a Walleth catheter with IUD in situ. The first two follow-ups were scheduled at the 3rd month and 6th month after insertion. If complete regression was achieved within 6 months, the follow-up interval was extended to 6 months thereafter. The primary outcome was the proportion of women with complete regression of EH. The secondary outcome was the time to complete regression.


1. Baseline characteristics

Twelve women with EH (simple hyperplasia without atypia 4, complex hyperplasia without atypia 7, complex hyperplasia with atypia 1) were included in this study. The summary of the baseline characteristics are shown in Table 1. The mean age was 39.1 years (range, 25 to 46 years). All women included were premenopausal. Six among the twelve women were nulliparous.

Table 1
Baseline characteristics

2. Endometrial regression after LNG-IUS insertion

The outcomes of the study is summarized in Table 2. All women developed a thin endometrium (≤4 mm) on TVS examination. All women achieved endometrial regression within 9 months after LNG-IUS insertion. In eight women out of twelve (66%), the regression was achieved at the 3rd month. The mean time to regression was 4.5 months. EH recurred in 1 patient whose LNG-IUS had been removed because of breast pains associated with LNG-IUS. Except for this case, there has been no other recurrence to date.

Table 2
Levonorgestrel releasing intrauterine system (LNG-IUS) insertion and follow-up of regression of endometrial hyperplasia

In the patient with CAH, complete regression was achieved at the 9th month, and has sustained until now for 21 months.


EH represents a spectrum from an exaggerated physiologic state to carcinoma in situ, as a result of unopposed estrogen stimulation in the absence of progestin influence. EH are important clinically because they may cause abnormal uterine bleeding, and precede or occur concurrently with endometrial carcinoma. Cytologic atypia is the most important risk factor for progression to carcinoma.

When it comes to EH without atypia, the malignant potential is low, the rate of spontaneous resolution is high1-3 and the therapeutic response to oral progesterone is also high. Therefore, hysterectomy for EH without atypia may be regarded as an over-treatment.4-8 According to three observational studies, the rate of spontaneous resolution for EH without atypia was 72% which was higher than 54% of atypical hyperplasias.2-4 Recently, conservative treatment has been considered to be acceptable when the strict follow-up is possible to detect cases of persistence, recurrence, and progress to carcinoma.15

Oral progesterone has been used to treat women with EH who wish to conserve the uterus. But some systemic side effects and poor compliance have been reported to be associated with oral progesterone. Compared with oral progesterone, LNG-IUS has been reported to have less systemic side effects and higher efficacy for the treatment of EH in many studies targeting the women of western countries.6-12 LNG-IUS has been regarded as a beneficial conservative treatment modality for non-atypical and atypical EH.8-12 But none of these studies have targeted Korean women. Thus, we do not have any reliable data for Korean women with EH. Besides, we had to consider the variation of treatment responses and the side effects of LNG-IUS according to Korean ethnicity. The results of this study support that LNG-IUS may also be a highly effective method for suppressing non-atypical and atypical EH in Korean women. The regression rate was 100%. The advantageous effects were observed within 9 months in all cases.

A significant proportion of the patients with non-atypical hyperplasia achieved regression at the 3rd month after LNG-IUS insertion. This success can be compared with the results of a recent long-term follow-up large observational European study, in which the regression rates of non-atypical hyperplasia and atypical hyperplasia were 90% and 54%, respectively.10 In this study, one patient with atypical hyperplasia achieved complete regression with LNG-IUS insertion at the 9th month. The results of our study targeting Korean women were in agreement with the beneficial effects of LNG-IUS on non-atypical and atypical EH observed in many other studies targeting western women.

There are weaknesses in this study. The first one is the small sample size of this study. Especially, there was only one case of atypical hyperplasia included in this study. The second one is that we conducted follow-up endometrial biopsies with the LNG-IUS in situ. The presence of the LNG-IUS in the uterine cavity may affect the accuracy of the endometrial biopsy. A large, long-term follow-up study may overcome these weaknesses. Nevertheless, this is the first study to evaluate the effectiveness of LNG-IUS for treatment of EH in Korean women, and the result was successful.


No potential conflict of interest relevant to this article was reported.


1. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia: a long-term study of "untreated" hyperplasia in 170 patients. Cancer. 1985;56:403–412. [PubMed]
2. Tabata T, Yamawaki T, Yabana T, Ida M, Nishimura K, Nose Y. Natural history of endometrial hyperplasia: study of 77 patients. Arch Gynecol Obstet. 2001;265:85–88. [PubMed]
3. Terakawa N, Kigawa J, Taketani Y, Yoshikawa H, Yajima A, Noda K, et al. The behavior of endometrial hyperplasia: a prospective study. Endometrial Hyperplasia Study Group. J Obstet Gynaecol Res. 1997;23:223–230. [PubMed]
4. Clark TJ, Neelakantan D, Gupta JK. The management of endometrial hyperplasia: an evaluation of current practice. Eur J Obstet Gynecol Reprod Biol. 2006;125:259–264. [PubMed]
5. Montgomery BE, Daum GS, Dunton CJ. Endometrial hyperplasia: a review. Obstet Gynecol Surv. 2004;59:368–378. [PubMed]
6. Marsden DE, Hacker NF. Optimal management of endometrial hyperplasia. Best Pract Res Clin Obstet Gynaecol. 2001;15:393–405. [PubMed]
7. Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol. 1989;160:126–131. [PubMed]
8. Wildemeersch D, Janssens D, Pylyser K, De Wever N, Verbeeck G, Dhont M, et al. Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. Maturitas. 2007;57:210–213. [PubMed]
9. Orbo A, Arnes M, Hancke C, Vereide AB, Pettersen I, Larsen K. Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-up study comparing effect of LNG-IUD and oral progestins versus observation only. Gynecol Oncol. 2008;111:68–73. [PubMed]
10. Varma R, Soneja H, Bhatia K, Ganesan R, Rollason T, Clark TJ, et al. The effectiveness of a levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of endometrial hyperplasia: a long-term follow-up study. Eur J Obstet Gynecol Reprod Biol. 2008;139:169–175. [PubMed]
11. Vereide AB, Kaino T, Sager G, Arnes M, Orbo A. Effect of levonorgestrel IUD and oral medroxyprogesterone acetate on glandular and stromal progesterone receptors (PRA and PRB), and estrogen receptors (ER-alpha and ER-beta) in human endometrial hyperplasia. Gynecol Oncol. 2006;101:214–223. [PubMed]
12. Vereide AB, Arnes M, Straume B, Maltau JM, Orbo A. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2003;91:526–533. [PubMed]
13. Lurain JR. Uterine cancer. In: Berek JS, editor. Berek & Novak's gynecology. 14th ed. Philadelphia: Lippincott Williams & Wilkins; 2007. pp. 1343–1402.
14. Phillips V, Graham CT, Manek S, McCluggage WG. The effects of the levonorgestrel intrauterine system (Mirena coil) on endometrial morphology. J Clin Pathol. 2003;56:305–307. [PMC free article] [PubMed]
15. Jadoul P, Donnez J. Conservative treatment may be beneficial for young women with atypical endometrial hyperplasia or endometrial adenocarcinoma. Fertil Steril. 2003;80:1315–1324. [PubMed]

Articles from Journal of Gynecologic Oncology are provided here courtesy of Asian Society of Gynecologic Oncology & Korean Society of Gynecologic Oncology and Colposcopy