Treatment of nonatypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system

OBJECTIVE: A "frameless" intrauterine drug delivery system that releases 14 microg/d of levonorgestrel was used to treat nonatypical and atypical endometrial hyperplasia in 12 women. STUDY DESIGN: This noncomparative study had up to 3 to 4 years of follow-up. RESULTS: The cure rate was 100%, as confirmed by repeat endometrial biopsy. CONCLUSION: This method could be considered an alternative to hysterectomy.     

The effectiveness of the levonorgestrel-releasing intrauterine system in menorrhagia: a systematic review

Objective To determine whether the levonorgestrel-releasing intrauterine device (LNG-IUS), licensed at present for contraceptive use, may reduce menstrual blood loss with few side effects. If effective, surgery could be avoided with consequent resource savings.
Methods A systematic review addressing the effectiveness and cost effectiveness of the LNG-IUS for menorrhagia was undertaken.
Results Five controlled trials and five case series were found which measured menstrual blood loss. Nine studies recorded statistically significant average menstrual blood loss reductions with LNG-IUS (range 74%–97%). Another showed reduction in menstrual disturbance score. The LNG-IUS was more effective than tranexamic acid, but slightly less effective than endometrial resection at reducing menstrual blood loss. In one study, 64% of women cancelled surgery at six months, compared with 14% of control group women. In another, 82% were taken off surgical waiting lists at one year. No cost effectiveness studies were found.
Discussion Small studies of moderate quality indicate the LNG-IUS is an effective treatment for menorrhagia. Costs may be less than for tranexamic acid in primary and secondary care. Although its use may reduce surgical waiting lists, cost effectiveness assessment requires longer follow up.
Conclusion Effectiveness and cost effectiveness relative to other treatments and the effect on surgical waiting lists can only be established in larger trials measuring patient-centred outcomes in women with menorrhagia.     

The combined GnRH-agonist and intrauterine levonorgestrel-releasing system treatment of complicated atypical hyperplasia and endometrial cancer: a pilot study

In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early-stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75?mg gonadotropin-releasing hormone agonist (GnRHa) ? leuproreline acetate depot every 4 weeks. After the third injection of 3.75?mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52?mg levonorgestrel (Mirena^®, Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well-differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75?mg of GnRHa every 4 weeks. After the third injection of 3.75?mg of GnRHa, we also inserted a GnRH-IUS (Mirena^®) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy.     

The effect of the levonorgestrel releasing intrauterine system on endometrial hyperplasia: An Australian study and systematic review

Background: The levonorgestrel intrauterine system (LNG-IUS) provides effective contraception and treatment for menorrhagia and is used to prevent endometrial hyperplasia (EH) in women taking unopposed oestrogens.
Aims: The aim of this study was to assess whether the LNG-IUS was also a safe and effective treatment for EH and to conduct a systematic review of the literature.
Methods: A retrospective record review was undertaken in a private gynaecology practice in Brisbane, Australia, and included all women with EH treated with hysterectomy, oral progestins or LNG-IUS between January 2004 and April 2007. Histopathological findings from hysterectomy specimens or endometrial biopsies were used to calculate rates of regression of the EH.
Results: Twenty-one women elected to have a hysterectomy and seven of those (33%) had no persisting hyperplasia at surgery. Twenty-six women had a LNG-IUS inserted at initial hysteroscopy dilatation and curettage or shortly afterwards; seven of those elected to proceed to hysterectomy when their diagnosis was known. Among ten women who used oral progestin treatment, 90% showed initial regression; two with recurrent EH were subsequently treated successfully with LNG-IUS. All 21 women (100%), including one with atypia, treated with LNG-IUS for more than seven weeks had normal endometrial histology on subsequent assessment. No women developed endometrial cancer. Pooled analysis of the published literature gave a 96% regression rate for non-atypical EH treated with LNG-IUS.
Conclusions: These data contribute further evidence that LNG-IUS is a safe and effective method for treating non-atypical EH. Whether LNG-IUS could provide a safe and cost-effective alternative to hysterectomy for atypical EH warrants further examination.     

Successful pregnancy following insertion of a levonorgestrel-releasing intrauterine system in two infertile patients with complex atypical endometrial hyperplasia

Two infertile patients are presented with complex atypical endometrial hyperplasia becoming pregnant following conservative treatment with a levonorgestrel-releasing intrauterine system (LNG-IUS) insertion. Histological morphology of endometrial samples after 6 months' exposure to LNG-IUS showed secretory or atrophic glands with decidualized stroma. Two healthy babies were born following ovulation induction after removal of the LNG-IUS.     

Safety of laparoscopy vs laparotomy in the surgical staging of endometrial cancer: a systematic review and metaanalysis of randomized controlled trials

The aim of the current study was to compare the safety of the laparoscopic vs abdominal approach to staging endometrial cancer. A search was conducted for randomized controlled trials that reported data from women with histologically confirmed endometrial cancer who underwent laparoscopic or abdominal surgery. An additional metaanalysis was performed. The primary endpoints were the rates of intraoperative and postoperative complications. A total of 8 original randomized controlled trials were included in the final analysis. No significant difference was observed in the relative risk (RR) for intraoperative complications between laparoscopy and laparotomy (RR, 1.25; 95% confidence interval, 0.99-1.56; P = .062). In contrast, a significant advantage of laparoscopy over laparotomy was obtained in terms of postoperative complications (RR, 0.71; 95% confidence interval, 0.63-0.79; P = .016). In comparison with abdominal surgery, the safety of the laparoscopic approach for surgical staging of endometrial cancer is similar in terms of intraoperative complications but results in fewer postoperative complications.     

The levonorgestrel-releasing intrauterine system and endometriosis staging

This study aims to determine whether the levonorgestrel-releasing intrauterine system can influence American Society for Reproductive Medicine endometriosis staging scores, as assessed through second-look laparoscopies, and to compare the results with those obtained with a GnRH agonist. Both treatments reduced the extent of pelvic endometriotic lesions in patients with chronic pelvic pain.     

The levonorgestrel-releasing intrauterine system: an updated review of the contraceptive and noncontraceptive uses

The levonorgestrel containing intrauterine system is an effective and safe form of long-term yet reversible birth control. Intrauterine contraception use in the United States fell dramatically after early studies reported an association between intrauterine contraception use and later tubal infertility. Subsequent evaluation suggests that these early studies were biased. Users often experience menstrual disturbances. Informing patients of these common side effects is important to improve compliance. In addition to its contraceptive effect, the levonorgestrel intrauterine system offers potential therapeutic benefits in other clinical contexts, including menorrhagia, symptomatic fibroids, endometriosis, and endometrial suppression.     

The slow levonorgestrel-releasing intrauterine system (LNG-IUS) 20 mcg/day: a literature review

The aim of the study is to present the mechanisms of action, indications, complications, contraindications and the necessary tests before the insertion of a levonorgestrel-releasing intrauterine system (Mirena). After a literature search in Pubmed, a narrative review in the field is presented.     

左炔诺孕酮宫内缓释系统治疗子宫内膜增生的疗效及安全性

目的:观察左炔诺孕酮宫内缓释系统(曼月乐)治疗子宫内膜增生的疗效及安全性。方法:151例子宫内膜增生症患者(排除子宫内膜癌)用曼月乐治疗,放置前和放置24个月内定期随访患者月经模式及血红蛋白水平;B超监测子宫内膜厚度、卵巢体积、子宫体积变化;子宫内膜病理学改变及卵巢激素水平变化。结果:放置后患者月经量明显减少,血红蛋白值明显升高,放置前血红蛋白水平为98.81±12.22g/L,放置后3,6,12,24个月血红蛋白值分别为116.53±9.62g/L,123.45±7.83g/L,127.26±8.02g/L,129.83±8.34g/L,各组间放置前后差异均有统计学意义(P<0.001);放置前子宫内膜厚度1.52±0.33cm,放置后3,6,12,24个月子宫内膜厚度分别为0.64±0.21cm,0.62±0.14cm,0.56±0.11cm,0.53±0.14cm,各组间放置前后差异均有统计学意义(P<0.001);放置曼月乐后6～12个月,患者子宫内膜病理显示子宫内膜增生过长表现消失,内膜呈分泌现象及间质蜕膜样改变明显;放置前后患者子宫、双侧卵巢体积及雌孕激素水平均无明显变化。结论:放置曼月乐可抑制子宫内膜增长及逆转增生的子宫内膜,副作用少,是治疗子宫内膜增生症安全、有效的方法,值得临床推广。     

Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma: a meta-analysis and systematic review of the literature

Objectives

To investigate the efficacy of progestin treatment to achieve pathological complete response (pCR) in patients with complex atypical endometrial hyperplasia (CAH) or early endometrial adenocarcinoma (EC).

Methods

A systematic search identified 3245 potentially relevant citations. Studies containing less than ten eligible CAH or EC patients in either oral or intrauterine treatment arm were excluded. Only information from patients receiving six or more months of treatment and not receiving other treatments was included. Weighted proportions of patients achieving pCR were calculated using R software.

Results

Twelve studies met the selection criteria. Eleven studies reported treatment of patients with oral (219 patients, 117 with CAH, 102 with grade 1 Stage I EC) and one reported treatment of patients with intrauterine progestin (11 patients with grade 1 Stage IEC). Overall, 74% (95% confidence interval [CI] 65-81%) of patients with CAH and 72% (95% CI 62-80%) of patients with grade 1 Stage I EC achieved a pCR to oral progestin. Disease progression whilst on oral treatment was reported for 6/219 (2.7%), and relapse after initial complete response for 32/159 (20.1%) patients. The weighted mean pCR rate of patients with grade 1 Stage I EC treated with intrauterine progestin from one prospective pilot study and an unpublished retrospective case series from the Queensland Centre of Gynaecologic Oncology (QCGC) was 68% (95% CI 45-86%).

Conclusions

There is a lack of high quality evidence for the efficacy of progestin in CAH or EC. The available evidence however suggests that treatment with oral or intrauterine progestin is similarly effective. The risk of progression during treatment is small but longer follow-up is required. Evidence from prospective controlled clinical trials is warranted to establish how the efficacy of progestin for the treatment of CAH and EC can be improved further.