Elsevier

Gynecologic Oncology

Volume 97, Issue 3, June 2005, Pages 924-927
Gynecologic Oncology

Case Report
Is levonorgestrel intrauterine system effective for treatment of early endometrial cancer? Report of four cases and review of the literature

https://doi.org/10.1016/j.ygyno.2004.10.031Get rights and content

Abstract

Background

Intrauterine progesterone therapy potentially provides a simple alternative treatment for women with Stage I Grade I endometrial cancers who are at high risk for surgery. The case histories of four women with early endometrial cancer primarily treated with levonorgestrel intrauterine system (Mirena) are reported and the literature reviewed.

Cases

Four women had Stage I grade 1 endometrial adenocarcinoma with positive progesterone receptor. All were assessed to be in American Society of anaesthesiologists risk class IV. After insertion of mirena intrauterine system, one woman (25%) had complete histological regression of disease within 6 months. One of three women who did not respond to treatment subsequently had a vaginal hysterectomy, which showed endometrial cancer with superficial myometrial invasion.

Conclusion

This report raises doubts about the effectiveness of intrauterine progesterone therapy as a definitive alternative for the treatment of early endometrial cancer.

Introduction

Endometrial cancer is the commonest gynecological malignancy in the United States. Nearly 40,000 cases were diagnosed in 2002 [1]. Almost 75% of cases present with FIGO stage I tumour. Therefore, traditional treatment by total abdominal hysterectomy with bilateral salpingooophorectomy achieves a 5-year survival of 75–90% [2]. However, severe or fatal peri-operative complications are observed in many patients with disease associated co-morbid conditions such as marked obesity, diabetes mellitus and hypertension [3]. Thus, the treatment planning of these patients often presents a major clinical challenge.

Endometrial cancer arises from tissue response to hormones. The relationship between epidemiological risk factors and the development of endometrial cancer can be explained by the unopposed estrogen hypothesis [4]. Progesterone by antagonizing the effect of estrogen on the endometrium may reverse this neoplastic process. Systemic progesterone treatment as primary therapy has been shown to be successful in premenopausal women with endometrial cancer who wish to retain their fertility potential [5], [6]. However, many women with high risk co-morbidity and endometrial cancer will not tolerate systemic progesterone due to associated adverse effects [7]. The development of a progesterone-containing intrauterine device (IUD) may offer a novel approach to deliver effective doses of progesterone locally to the endometrium, potentially avoiding any associated systemic adverse effects in these high-risk women. ‘Progestasert’, a progesterone containing IUD, has recently been used as primary treatment for early endometrial cancer in women at high risk for perioperative complication [8]. ‘Progestasert’ is not available in the United Kingdom. Instead, ‘Mirena’ (Schering Health Care Ltd, West Sussex England), a levonorgestrel (LNG) containing intrauterine system (IUS), is available commercially for contraception. As opposed to limited (12 months) effective lifetime for ‘Progestasert’, ‘Mirena’ delivers 20 μg levonorgestrel daily for at least 5 years. There is no data available comparing histological effects of progesterone versus levonorgestrel. However, use of ‘Mirena’ IUS resulted in complete histological regression of endometrial hyperplasia [9] and compared to ‘Progestasert’ displayed a more uniform response throughout the whole thickness of endometrium including the basal layer [10].

We report four case of clinical stage I, grade 1 endometrial cancer in women at high risk for perioperative complication treated primarily with ‘Mirena’ IUS and followed up 18–36 months. To our knowledge, there is no published report in the English literature describing use of ‘Mirena’ IUS in the treatment of endometrial cancer. We have also contacted the medical information scientist at Schering Ltd. They were unaware of the use of ‘Mirena’ IUS as treatment for endometrial cancer.

Section snippets

Case report

All women were seen during February 2000 to April 2002 at the Gynaecological Cancer Centre of Saint Mary's Hospital, Portsmouth, with histologically confirmed grade 1 endometrial cancer. All except case 3 underwent hysteroscopy and endometrial biopsy whereas case 3 had endometrial biopsy alone. There was no clinical or imaging (transvaginal sonogram and chest radiograph) evidence of extrauterine disease. They all had associated medical conditions, which placed them in American Society of

Discussion

Surgery continues to be the mainstay of treatment for potentially curable early endometrial cancer. However, women with associated medical conditions as described in this report are at exceptionally high risk even with advances in anaesthetic and surgical techniques. This remains a clinical dilemma when planning treatment. Do we have simple, safer but effective alternative treatment for this group of women? Hormonal manipulation is a logical concept as endometrial cancer arises from hormone

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