A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women. A comparative study of the levonorgestrel-releasing intrauterine system Mirena versus the Copper T380A intrauterine device during lactation: breast-feeding performance, infant growth and infant development. Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel-releasing intrauterine system: a randomised controlled trial. Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia. Treatment of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection. A randomized clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. A randomised trial comparing the levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study.
To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen.
                Randomised controlled trial.
                A tertiary teaching hospital.
                One hundred and thirteen women (66 premenopausal/47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy.
                Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen.
                De novo endometrial pathology at 1 year of tamoxifen.
                Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P= 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P= 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year.
                LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer. Mirena is a levonorgestrel-releasing intrauterine system (LNG-IUS) that provides highly effective and long-acting progestogen-only contraception.
                The objective of this study was to analyze the possible effects of using LNG-20 microg IUS on breast-feeding performance, infant growth and infant development during the first postpartum year as compared with the Copper T380A intrauterine device (Cu T380A IUD).
                This study is a prospective, controlled and randomized trial.
                The study was conducted at the Department of Obstetrics and Gynecology, Assiut University Hospital, Egypt.
                Three hundred twenty lactating women asking for initiation of contraception during the early postpartum stage were assigned randomly into two groups, the LNG-20 microg IUS group (n=163) and the Cu T380A group (n=157). The insertions were done 6-8 weeks postpartum. Each participant was followed up at three monthly intervals after insertion and until the first birthday of her baby. During these visits, the breast-feeding pattern was assessed, certain infant physical growth parameters were measured and a set of infant development tests was performed.
                No pregnancy occurred in both groups. There were no significant differences in the net continuation rates between the two groups (89.3 for LNG-IUS vs. 90.9 for Cu T380A). The LNG-20 microg IUS group had comparable rates of breast-feeding continuation, complete weaning, full breast-feeding and partial breast-feeding, with the Cu-IUD group. No statistically significant differences were found between groups with regard to all infant physical growth parameters and various infant development tests.
                The findings of the current study confirm that the use of LNG-20 microg IUS during the first postpartum year in lactating women provides highly effective and acceptable contraception and does not negatively influence breast-feeding or the growth and development of breast-fed infants. Tamoxifen is currently the most commonly used adjuvant treatment for breast cancer, however, it frequently causes episodes of unscheduled uterine bleeding, which could be associated with proliferative changes of the endometrium, or even endometrial cancer. We aimed to assess whether a levonorgestrel intrauterine system could modulate the uterine responses to tamoxifen. We also aimed to assess women's tolerance of the screening procedures, the insertion, removal, and potential side-effects of the device.
                We did a randomised controlled trial, in which postmenopausal women who had had at least 1 year of adjuvant tamoxifen treatment and who were undergoing regular follow-up for breast cancer were randomly assigned to either endometrial surveillance alone, or endometrial surveillance before and after insertion of the levonorgestrel intrauterine system for 12 months. We assessed tolerance of the surveillance procedures and the device with visual analogue scales.
                Baseline assessment showed only benign uterine changes in all women (n=122). Hysteroscopic assessment indicated a uniform decidual response (confirmed histologically in 40 of 41 cases) in all women fitted with the intrauterine system; there were no new polyps in these women and 13% had fewer fibroids than in controls. Both screening procedures and device were well tolerated. There was an excess of bleeding in the women fitted with intrauterine systems but this resolved to a baseline similar to those receiving surveillance only.
                The levonorgestrel-releasing intrauterine system had a protective action against the uterine effects of tamoxifen. The effectiveness of this device in preventing uterine changes in the endometrium needs to be assessed in the context of decreasing the need for repeated investigations of postmenopausal bleeding in women taking tamoxifen. To compare the effectiveness of endometrial thermal ablation and the levonorgestrel intrauterine system (LNG-IUS) in the management of menorrhagia.
                Fifty women attending a gynaecology clinic at a District General Hospital in south-west England were randomised to either surgical treatment using thermal ablation (Thermochoice, Gynecare) or medical treatment using a LNG-IUS (Mirena, Schering Healthcare). A pictorial menstrual chart was completed pre-insertion/operatively and again at 6 months post-insertion/operatively. Non-parametric tests (Mann-Whitney) were used for statistical analysis.
                Follow-up analysis was possible in 23 women in the Thermochoice group and 21 women in the Mirena group. The menstrual scores were slightly higher in the Thermochoice group (median 101) than the Mirena group (median 75) (P=0.025) pre-insertion/operatively but this difference was lost post-insertion/operatively (P=0.689) with median menstrual scores of 27 for the Thermochoice group and 19 for the Mirena group, respectively.
                Both Thermochoice endometrial ablation and a Mirena LNG-IUS are equally effective in the management of menorrhagia. The choice of treatment should be tailored to the woman's needs and preferences. Treatment of menorrhagia with levonorgestrel intrauterine system (LNG IUS) and transcervical resection.
                An open, therapeutic, randomized study.
                Central county hospital specializing in hysteroscopy.
                Two parallel groups of 30 subjects each.
                Thirty patients had a LNG IUS inserted within the first 7 days of menses; 29 patients underwent endometrial resection.
                A 12-month follow-up of menstrual blood loss and adverse events were evaluated.
                LNG IUS group: 13 patients reported one or more pelvic adverse events, bleeding disorders (n = 6), abdominal pain (n = 4), breast tenderness (n = 3), headache, acne (n = 2), and mood changes (n = 1). Six patients discontinued treatment because of irregular bleeding (n = 3), pain (n = 2), and acne (n = 1). In both groups, general feeling of genital health increased with Visual Analogue Scale score. Nine patients reported adverse events. This included pelvic pain indicating inflammation (n = 4), bleeding (n = 3), vaginitis (n = 1), and ulceration (n = 1). Treatment success at 12 months was achieved in 20 (67%) of the 30 patients in the LNG IUS group and in 26 (90%) of the 29 patients in the transcervical resection group. Adverse events were more often reported in the LNG IUS group.
                Both treatments effectively reduced the menstrual blood loss. Furthermore, the LNG IUS treatment is reversible and has no operative hazards. To compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) with that of a low-dose combined oral contraceptive (COC) in reducing fibroid-related menorrhagia.
                In this single-center, open, randomized clinical trial, 58 women with menorrhagia who desired contraception were randomized to receive a LNG-IUS or COC. The outcomes included treatment failure, defined as the need for another treatment; menstrual blood loss (MBL) by the alkaline hematin method and a pictorial assessment chart (PBAC); hemoglobin levels; and "lost days."
                Treatment failed in 6 women (23.1%) in the LNG-IUS group and 11 (37.9%) in the COC group, for a hazard ratio of 0.46 (95% CI, 0.17-1.17, P=0.101). Using the alkaline hematin test, the reduction of MBL was significantly greater in the LNG-IUS group (90.9% ± 12.8% vs 13.4% ± 11.1%; P<0.001). Using PBAC scores, the reduction was also significantly greater in the LNG-IUS group (88.0% ± 16.5% vs 53.5% ± 5 1.2%; P=0.02). Moreover, hemoglobin levels increased from 9.7 ± 1.9g/dL to 11.7 ± 1.2g/dL (P<0.001) and lost days decreased from 8.2 ± 3.3 days to 1.3 ± 1.5 days (P=0.003) in the LNG-IUS group.
                Although the rate of treatment failure was similar in both groups, the LNG-IUS was more effective in reducing MBL than the COC in women with fibroid-related menorrhagia.
                Copyright Â© 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. The objective of this multicentre randomized, controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months.
                Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n = 39) or GnRH analogue (n = 43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period.
                CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups (P > 0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease (P < 0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life.
                Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive. To compare the levonorgestrel intrauterine system (LNG-IUS) (Mirena); Schering Co., Turku, Finland) and thermal balloon ablation (Thermachoice; Gynecare Inc., Menlo Park, CA, USA) for the treatment of heavy menstrual bleeding.
                An open, pragmatic, prospective randomised trial.
                A menstrual disorders clinic at National Women's Hospital, Auckland, New Zealand.
                Seventy-nine women with heavy menstrual bleeding randomised to the LNG-IUS (40 women) or the thermal balloon ablation (39 women).
                Women were randomised to treatment with the LNG-IUS or thermal balloon ablation and followed up by a postal and telephone questionnaire.
                Menstrual loss measured by a pictorial bleeding assessment chart (PBAC) at 3, 6, 12 and 24 months. Patient satisfaction, quality of life and menstrual symptoms were assessed by questionnaire administered at 3, 6, 12 and 24 months. Treatment side effects and treatment failures were also recorded.
                Both the treatments resulted in a significant reduction in PBAC scores. At 12 and 24 months, median PBAC scores were significantly lower in women treated with the LNG-IUS compared with women treated by thermal balloon ablation (11.5 versus 60.0 at 12 months [P= 0.002]; 12.0 versus 56.5 [P= 0.002] at 24 months). At 24 months, nine (35%) women still using the LNG-IUS had amenorrhoea compared with one (5%) woman successfully treated by thermal balloon ablation (P = 0.025). There were no significant differences in patient satisfaction between two treatments during follow up. Treatment failed in 11 (28%) women using the LNG-IUS and in 10 (26%) women treated with thermal balloon ablation. Overall, women in both groups showed an increased quality of life as a result of the treatment, with Short Form-36 scores increasing from 63.7 at randomisation to 76.1 at 24 months.
                At 12 and 24 months of follow up, women with heavy menstrual bleeding treated with the LNG-IUS have significantly lower PBAC scores than women treated with thermal balloon ablation. Both the treatments resulted in a significant increase in overall quality of life, but there were no significant differences between either treatment in quality of life, patient satisfaction or the number of women requesting an alternative treatment during 24 months of follow up. To establish an optimal adjuvant therapy for intermediate- and high-risk endometrial cancer patients, we conducted a multi-center randomized phase III trial of adjuvant pelvic radiation therapy (PRT) versus cyclophosphamide-doxorubicin-cisplatin (CAP) chemotherapy in women with endometrioid adenocarcinoma with deeper than 50% myometrial invasion.
                Among 385 evaluated patients, 193 patients received PRT and 192 received CAP. The PRT group received at least 40 Gy. The CAP group received cyclophosphamide (333 mg/m2), doxorubicin (40 mg/m2) and cisplatin (50 mg/m2) every 4 weeks for 3 or more courses.
                No statistically significant differences in progression-free survival (PFS) and overall survival (OS) were observed. The 5-year PFS rates in the PRT and CAP groups were 83.5% and 81.8% respectively, while the 5-year OS rates were 85.3% and 86.7% respectively. These rates were also not significantly different in a low- to intermediate-risk group defined as stage IC patients under 70 years old with G1/2 endometrioid adenocarcinoma. However, among 120 patients in a high- to intermediate-risk group defined as (1) stage IC in patients over 70 years old or with G3 endometrioid adenocarcinoma or (2) stage II or IIIA (positive cytology), the CAP group had a significantly higher PFS rate (83.8% vs. 66.2%, log-rank test P=0.024, hazard ratio 0.44) and higher OS rate (89.7% vs. 73.6%, log-rank test P=0.006, hazard ratio 0.24). Adverse effects were not significantly increased in the CAP group versus the PRT group.
                Adjuvant chemotherapy may be a useful alternative to radiotherapy for intermediate-risk endometrial cancer.
The Mirena LNG-IUS appears to prevent the development of benign endometrial polyps in breast cancer patients taking tamoxifen, over a one-year period. There is no clear evidence from the available randomised controlled trials that LNG-IUS prevents endometrial hyperplasia or adenocarcinoma in these patients. Larger studies are necessary to assess the effects of LNG-IUS in preventing endometrial hyperplasia and endometrial cancer, and to determine whether LNG-IUS might have an impact on the risk of breast cancer recurrence.