Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia. Levonorgestrel-releasing intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding. A randomized controlled trial of levonorgestrel releasing IUD and thermal balloon ablation in the treatment of menorrhagia. Treatment of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection. Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial. A randomised trial comparing the levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding. Randomised comparative trial of the levonorgestrel intrauterine system and mefenamic acid for the treatment of idiopathic menorrhagia: a multiple analysis using total menstrual fluid loss, menstrual blood loss and pictorial blood loss assessment charts. The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia. Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia. Open randomised study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy.
To compare the efficacy and acceptability of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia.
                A randomised comparative parallel group study.
                Gynaecology outpatient clinic in a teaching hospital.
                Forty-four women with heavy regular periods and a measured menstrual blood loss exceeding 80 ml.
                Twenty-two women had a levonorgestrel intrauterine system inserted within the first seven days of menses, and 22 women received norethisterone (5 mg three times daily) from day 5 to day 26 of the cycle for three cycles.
                The main outcome measure was the change in objectively assessed menstrual blood loss after three months of treatment.
                When menstrual blood loss at three months was expressed as a percentage of the control, the levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the women in the levonorgestrel intrauterine system group wished to continue with the treatment, compared with only 22% of the norethisterone group.
                Both the levonorgestrel intrauterine system and oral norethisterone in this regimen provided an effective treatment for menorrhagia in terms of reducing menstrual blood loss to within normal limits. The levonorgestrel intrauterine system was associated with higher rates of satisfaction and continuation with treatment, and thus offers an effective alternative to currently available medical and surgical treatments for menorrhagia. To compare the effect of a levonorgestrel-releasing intrauterine device with that of endometrial resection on menstrual bleeding, patient satisfaction, and quality of life in menorrhagic women during 12 months of follow-up.
                Seventy premenopausal women with dysfunctional uterine bleeding were enrolled in a prospective, open, parallel-group, controlled trial. They were randomized to either insertion of an intrauterine system releasing 20 micrograms/day of levonorgestrel (n = 35) or endometrial resection (n = 35). The women were evaluated at baseline, and thereafter, uterine bleeding was assessed monthly with a pictorial blood loss assessment chart. Clinical gynecologic examination was performed bimonthly, and the hematologic variables were measured at 6 and 12 months. On the latter occasion, the women were requested to rate the degree of satisfaction with the effect of their treatment and to complete the Short Form 36 General Health Survey questionnaire.
                Recurrent menorrhagia was observed at 12 months in four women in the intrauterine device group (including two with partial expulsion of the device) and in three women in the resection group. Compared with baseline values, at 1 year, the pictorial blood loss assessment chart score was reduced by 79% in the former group and by 89% in the latter. Amenorrhea or hypomenorrhea at 12 months was reported by 65% of the women with an intrauterine device compared with 71% who underwent endometrial resection. The degree of satisfaction with treatment was high in both groups, with 29 of 34 (85%) women being satisfied or very satisfied in the intrauterine device group versus 33 of 35 (94%) in the resection group. Health-related quality of life perception was not significantly different in the two treatment groups.
                Somewhat less satisfactory results were obtained with a levonorgestrel-releasing intrauterine system compared with endometrial resection for dysfunctional uterine bleeding at 1 year of follow-up. Our aim was to compare the treatment of menorrhagia either with a levonorgestrel-releasing intrauterine device or with endometrial thermal balloon ablation. The primary endpoints of evaluation were menstrual blood flow reduction and the increase in hemoglobin values, while the secondary end points were adverse side effects; health related quality of life. After randomization, 36 women underwent outpatient thermal balloon ablation under local anesthesia and an intrauterine device releasing 20 microgram/day of levonorgestrel, were inserted within the first 7 days of menses to 36 women. Both techniques were found to be significantly effective in reducing the menstrual blood loss but in comparison thermal balloon ablation was more effective in Deltamean +/- SD decrease of pictorial sores (388.2 +/- 21 vs 343 +/- 27; p < 0.001). We noted a significant but similar increases in Deltamean +/- SD hemoglobin values (3.9 +/- 1.7 vs 3.7 +/- 1.4; p:.21). Patients treated by thermal balloon ablation reported fewer side effects and perceived a higher health related quality of life in physical role functioning. At one year of follow-up, the medicated device was effective but not as effective as thermal balloon ablation in reducing the menstrual blood loss. However it was found to be as effective as thermal balloon ablation in increasing the hemoglobin values. The side effect profile of the medicated device may alter its acceptability by reducing the perceived health related quality of life in menorrhagic women with no desire for further childbearing. 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. Heavy menstrual blood loss is a common reason for women to seek medical care. The levonorgestrel-releasing intrauterine system (IUS) is an effective medical treatment for menorrhagia. We report a randomised comparison of this approach with hysterectomy in terms of the quality of life of women with menorrhagia and cost-effectiveness.
                Of 598 women referred with menorrhagia to five university hospitals in Finland, 236 were eligible and agreed to take part. They were randomly assigned treatment with the levonorgestrel-releasing IUS (n=119) or hysterectomy (n=117). The amount of menstrual blood loss was objectively measured. The primary outcome measure was health-related quality of life at 12-month follow-up. Analyses were by intention to treat.
                In the group assigned the levonorgestrel-releasing IUS, 24 (20%) women had had hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation. Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change 0.10 [95% CI 0.06-0.14] in both groups) as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that women with hysterectomy suffered less pain. Overall costs were about three times higher for the hysterectomy group than for the IUS group.
                The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy in treatment of this disorder. 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 compare the efficacy and tolerability of the levonorgestrel intrauterine system (LNG IUS) with mefenamic acid in the management of objective idiopathic menorrhagia.
                Phase III, Single centre, open, randomised, comparative, parallel group study.
                District General Hospital in the United Kingdom.
                Fifty-one women with objective menorrhagia.
                Twenty-five women randomised to receive the LNG IUS and 26 to oral mefenamic acid for six cycles.
                Change from baseline in menstrual blood loss (MBL), total menstrual fluid loss (TMFL) and pictorial blood loss assessment chart (PBAC) score at the third and sixth cycle of treatment.
                After six cycles the median menstrual blood loss was 5 mL in the LNG IUS group and 100 mL in the mefenamic acid group (P < 0.001). Median TMFL was 27 mL in the LNG IUS group and 157 mL in the mefenamic acid group (P < 0.001). Median PBAC score was 25 in the LNG IUS group and 159 in the mefenamic acid group. Changes in menstrual blood loss correlated strongly to changes in TMFL (r= 0.88) but PBAC correlated less well to blood loss and total fluid loss (r= 0.53 and r= 0.58).
                Both the LNG IUS and mefenamic acid significantly decreased menstrual blood loss, TMFL and PBAC scores. The LNG IUS produced greater reductions in all parameters than mefenamic acid. Comparison of the different measurements suggests that TMFL assessment may be an easier and a more relevant measure of symptom severity than menstrual blood loss. The effects of four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200 mg daily (n = 6), mefenamic acid, 500 mg three times daily during menses (n = 8), norethisterone, 5 mg twice daily from day 15-25 of the cycle (n = 8) or a progesterone-impregnated coil releasing 65 micrograms progesterone daily (n = 8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefenamic acid (P = 0.05, n = 6) and the progesterone coil (P less than 0.05, n = 6), and was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG concentrations in either the mefenamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF2 alpha and "total" PG (6oxo PGF1 alpha + PGE + PGF2 alpha)-P = 0.05. Whereas the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continuous administration of progesterone throughout the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism. 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. To assess whether the levonorgestrel intrauterine system could provide a conservative alternative to hysterectomy in the treatment of excessive uterine bleeding.
                Open randomised multicentre study with two parallel groups: a levonorgestrel intrauterine system group and a control group.
                Gynaecology departments of three hospitals in Finland.
                Fifty six women aged 33-49 years scheduled to undergo hysterectomy for treatment of excessive uterine bleeding.
                Women were randomised either to continue with their current medical treatment or to have a levonorgestrel intrauterine system inserted.
                Proportion of women cancelling their decision to undergo hysterectomy.
                At 6 months, 64.3% (95% confidence interval 44.1 to 81.4%) of the women in the levonorgestrel intrauterine system group and 14.3% (4.0 to 32.7%) in the control group had cancelled their decision to undergo hysterectomy (P < 0.001).
                The use of the levonorgestrel intrauterine system is a good conservative alternative to hysterectomy in the treatment of menorrhagia and should be considered before hysterectomy or other invasive treatments.
The levonorgestrel-releasing intrauterine device (LNG IUS) is more effective than cyclical norethisterone (for 21 days) as a treatment for heavy menstrual bleeding. Women with an LNG IUS are more satisfied and willing to continue with treatment but experience more side effects, such as intermenstrual bleeding and breast tenderness. 
The LNG IUS results in a smaller mean reduction in menstrual blood loss (as assessed by the PBAC chart) than endometrial ablation but there is no evidence of a difference in the rate of satisfaction with treatment. Women with an LNG IUS experience more progestogenic side effects compared to women having TCRE for treatment of their heavy menstrual bleeding but there is no evidence of a difference in their perceived quality of life. 
The LNG IUS treatment costs less than hysterectomy but there is no evidence of a difference in quality of life measures between these groups. 
There are no data available from randomised controlled trials comparing progesterone-releasing intrauterine systems to either placebo or other commonly used medical therapies for heavy menstrual bleeding.