Levonorgestrel-releasing Intrauterine System Treatment Research Articles

Comparison of the treatment efficacies of HIFU, HIFU combined with GnRH-a, and HIFU combined with GnRH-a and LNG-IUS for adenomyosis: A systematic review and meta-analysis.

To compare the treatment efficacies of high-intensity focused ultrasound (HIFU), HIFU combined with gonadotrophin-releasing hormone agonist (GnRH-a), and HIFU combined with GnRH-a and levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis. We conducted a literature search in SCIENCE DIRECT, COCHRANE LIBRARY, WILLEY ONLINE LIBRARY, PUBMED, and TAYLOR FRANCIS. A total of 471 articles identified, 12 were included in a systematic review, and 11 of them deemed quantitively eligible included in the meta-analysis. The efficacies of the three treatment regimens were assessed using the dysmenorrhea and menstrual scores at 3, 6, 12, 24 months. Of the three regimens, HIFU combined with GnRH-a and LNG-IUS provides the best outcome. On dysmenorrhea score at 6 months there was significantly different higher heterogeneity with P<0.00001 (I2=100% WMD 21.44 [6.34, 36.53]) with statistical significance P=0.005. At 12 months there was significantly different higher heterogeneity P<0.00001 (I2=100% WMD 23.47 [6.00, 40.94]) with statistically significant P<0.008. At 24 months there was significantly different higher heterogeneity P<0.0005 (I2=92% WMD 6.05 [4.81, 7.30]) with statistical significance P<0.00001. HIFU combined with GnRH-a and LNG-IUS on menstrual score at 3 months was significantly different higher heterogeneity with P<0.00001 (I2=100% WMD 56.23 [16.01, 96.45]) with statistical significance P=0.006. At 6 months there was significantly different higher heterogeneity P<0.00001 (I2=99% WMD 93.86 [64.15, 123.57]) with statistical significance P<0.00001. At 12 months there was significantly different higher heterogeneity P<0.00001 (I2=99% WMD 97.13 [67.81, 126.46]) with statistical significance P<0.00001 compared to treatments with only HIFU and HIFU combined with GnRH-a. HIFU combined with GnRH-a and LNG-IUS treatment is more effective than only HIFU monotherapy and HIFU combined with GnRH-a.

Levonorgestrel-releasing intrauterine system vs. systemic medication or blank control for women with dysmenorrhea: Systematic review and meta-analysis of randomized controlled trials.

To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with systemic medication or blank control in the treatment of dysmenorrhea. PubMed, EMBASE, the China National Knowledge Infrastructure (CNKI) and Wanfang Data were searched to collect randomized controlled trials (RCTs) comparing LNG-IUS with systemic medication or blank control among women diagnosed with primary dysmenorrhea or secondary dysmenorrhea (adenomyosis or endometriosis) from inception to 2020.04. Der Simonian-Laird random-effect model was used to pool data. Seventy-one RCTs (6551 patients) were included. Overall bias risk was medium. Sixty-two articles enrolled patients with adenomyosis; LNG-IUS significantly reduced the visual analogue scale (VAS) score compared with the systemic medication group among adenomyosis women at 3 months (standardized mean difference (SMD) = -0.81, 95% confidence interval (CI) -1.22 to -0.40); 6 months (SMD = -1.25, 95%CI: -1.58 to -0.92); 9 months (SMD = -1.23, 95%CI: -1.63 to -0.83); 12 months (SMD = -1.66, 95%CI: -2.14 to -1.18). No difference was found in the incidence of irregular vaginal bleeding (16 RCTs; RR = 0.91, 95%CI: 0.62-1.33, P = 0.63, I 2 = 4%) and other adverse outcomes. Sensitivity analysis regarding randomization methods was robust. Nine RCTs enrolled endometriosis women. Pooling results showed no significant difference between LNG-IUS and systemic medication treatment in terms of VAS at 6 months (SMD = -0.27, 95% CI: -0.97-0.43). Moreover, LNG-IUS was associated with higher risk of irregular vaginal bleeding (26.8% vs. 0). LNG-IUS was associated with a reduced severity of dysmenorrhea compared with systemic medication; it was also beneficial for better control of menstrual blood loss and fewer adverse outcomes. Owing to small sample sizes, further well-designed RCTs are warranted to confirm these findings and long-term effects of LNG-IUS in the treatment of dysmenorrhea. https://www.crd.york.ac.uk/prospero/, identifier: CRD42021228343.

Levonorgestrel-Releasing Intrauterine System Improves Menorrhagia-Related Quality of Life in Patients with Symptomatic Adenomyosis.

Levonorgestrel-releasing intrauterine system (LNG-IUS) relieves dysmenorrhea and heavy menstrual bleeding (HMB) in adenomyosis. However, its efficacy on health-related quality of life (HR-QOL) in patients with symptomatic adenomyosis remains unclear. The menorrhagia multi-attribute scale (MMAS), which measures HR-QOL improvement through the treatment of HMB, has never been used for evaluating menorrhagia-specific HR-QOL in patients with symptomatic adenomyosis. Hence, this study aimed to investigate the efficacy of LNG-IUS in improving menorrhagia-specific HR-QOL in these patients using the MMAS. The participants were diagnosed by magnetic resonance imaging. We also assessed the relationships between menorrhagia-specific HR-QOL, blood hemoglobin levels, and the degree of dysmenorrhea before and during LNG-IUS treatment. The LNG-IUS treatment improved the menorrhagia-specific HR-QOL more effectively in incipienttype adenomyosis than in advanced type adenomyosis. The efficacy of LNG-IUS treatment on dysmenorrhea evaluated by the visual analog scale score tended to be better in the incipient type than in the advanced type. By the treatment of LNG-IUS, the blood hemoglobin level was not improved in the advanced type but in the incipient type. Furthermore, dysmenorrhea and HMB-related anemia were associated with HR-QOL impairment, and LNG-IUS treatment may improve the HR-QOL by relieving the symptoms. In conclusion, the effectiveness of LNG-IUS on HR-QOL is decreased by advanced adenomyosis. Thus, magnetic resonance imaging use should be reinforced to predict LNG-IUS efficacy in improving the HR-QOL of patients with adenomyosis.

Clinical Efficacy of Dienogest versus Levonorgestrel-Releasing Intrauterine System for Adenomyosis.

Objective The aim of this study is to evaluate the efficacy of dienogest versus levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis. Methods In this retrospective study, 85 patients with adenomyosis treated in The First Affiliated Hospital of Zhengzhou University from May 2019 to May 2021 were recruited and assigned, via the random number table method at a ratio of 1 : 1, to receive either dienogest (observation group, n = 41) or LNG-IUS (control group, n = 44). The patients presented with dysmenorrhea, menorrhagia, and infertility. The treatment outcome was evaluated using visual analogue scale (VAS) scores, menstrual volume, uterine volume, endometrial thickness, and adverse reactions. Results After treatment, the VAS score, menstrual volume, and endometrial thickness were significantly decreased in both groups (P < 0.05). After 3, 6, and 12 months of treatment, patients receiving dienogest showed significantly lower VAS scores compared to those treated with LNG-IUS (P < 0.05). After 6 and 12 months of treatment, patients receiving dienogest were also found to have a significantly better control of menstrual volume compared to those receiving LNG-IUS (P < 0.05). Irregular vaginal bleeding was mainly seen in the first 3 months of treatment with dienogest. The incidence of irregular vaginal bleeding lasting more than 6 months was lower with LNG-IUS treatment than with dienogest (P < 0.05), and it decreased in both groups as the duration of treatment increased. Conclusion Dienogest effectively alleviates dysmenorrhea, relieves pelvic pain, dyspareunia, and reduces menstrual flow in patients with adenomyosis, with few adverse effects and a high safety profile.

Comparison of Levonorgestrel-releasing Intrauterine System (LNG-IUS) against Laparoscopic Assisted Supracervical Hysterectomy (LASH) for menorrhagia treatment: An economic evaluation

BackgroundThis economic evaluation and literature review was conducted with the primary aim to compare the cost-effectiveness of laparoscopic assisted supracervical hysterectomy (LASH) with NICE's gold-standard treatment of Levonorgestrel-releasing intrauterine system (LNG-IUS) for menorrhagia. Materials and methodsA cost-utility analysis was conducted from an NHS perspective, using data from two European studies to compare the treatments. Individual costs and benefits were assessed within one year of having the intervention. An Incremental Cost-Effectiveness Ratio (ICER) was calculated, followed by sensitivity analysis. Expected Quality Adjusted Life Years (QALYS) and costs to the NHS were calculated alongside health net benefits (HNB) and monetary net benefits (MNB). ResultsA QALY gain of 0.069 was seen in use of LNG-IUS compared to LASH. This yielded a MNB between -£44.99 and -£734.99, alongside a HNB between –0.0705 QALYs and –0.106 QALYS. Using a £20,000-£30,000/QALY limit outlined by NICE,this showed the LNG-IUS to be more cost-effective than LASH, with LASH exceeding the upper bound of the £30,000/QALY limit. Sensitivity analysis lowered the ICER below the given threshold. ConclusionsThe ICER demonstrates it would not be cost-effective to replace the current gold-standard LNG-IUS with LASH, when treating menorrhagia in the UK. The ICER's proximity to the threshold and its high sensitivity alludes to the necessity for further research to generate a more reliable cost-effectiveness estimate. However, LASH could be considered as a first line treatment option in women with no desire to have children.

Predictive factors for failure of the levonorgestrel releasing intrauterine system in women with heavy menstrual bleeding

BackgroundThis study was conducted to identify factors that are associated with failure of treatment using the levonorgestrel releasing intrauterine system (LNG-IUS) in women with heavy menstrual bleeding.MethodsFor this study, data of a cohort of women treated with an LNG-IUS was used. Women who suffered from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future child wish, were recruited in hospitals and general practices in the Netherlands. Eight potential prognostic baseline variables (age, body mass index, caesarean section, vaginal delivery, previous treatment, anticoagulant use, dysmenorrhea, and pictorial blood assessment score) were analyzed using univariable and multivariable regression models to estimate the risk of failure. The main outcome measure was discontinuation of the LNG-IUS within 24 months of follow up, defined as removal of the LNG-IUS or receiving an additional intervention.ResultsA total of 209 women received the LNG-IUS, 201 women were included in the analyses. 93 women (46%) discontinued LNG-IUS treatment within 24 months. Multivariable analysis showed younger age (age below 45) (adjusted RR 1.51, 95% CI 1.10–2.09, p = .012) and severe dysmenorrhea (adjusted RR 1.36, 95% CI 1.01–1.82, p = .041) to be associated with a higher risk of discontinuation.ConclusionsHigh discontinuation rates are found in women who receive an LNG-IUS to treat heavy menstrual bleeding. A younger age and severe dysmenorrhea are found to be risk factors for discontinuation of LNG-IUS treatment. These results are relevant for counselling women with heavy menstrual bleeding.

Ultrasound-guided transvaginal radiofrequency ablation combined with levonorgestrel-releasing intrauterine system for symptomatic uterine adenomyosis treatment

Objective To evaluate the clinical outcomes of transvaginal ultrasound-guided radiofrequency ablation (RFA) combined with a levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of symptomatic uterine adenomyosis. Methods Patients with symptomatic uterine adenomyosis treated with ultrasound-guided RFA in combined with an LNG-IUS from January 2013 to January 2016 and followed up for 3 years after treatment were selected. Assessment endpoints included the uterine volume reduction rate, dysmenorrheal score, symptom severity score and adverse events. Results Among the 72 patients, 64 completed the 3-year follow-up evaluations after treatment. No LNG-IUS expulsion was reported. Dysmenorrhea and symptom severity scores statistically significantly declined after the combined treatment of RFA and LNG-IUS was administered. The uterine volume significantly decreased, and the average reduction rate was 55%. Conclusion Ultrasound-guided RFA combined with an LNG-IUS might be a simple, safe and effective alternative for the treatment of symptomatic adenomyosis.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

Analysis of the effect and safety of levonorgestrel-releasing intrauterine system on patients with breast cancer who take tamoxifen

Objective To analyze the effect and safety of levonorgestrel-releasing intrauterine system(LNG-IUS) for the premenopausal patients with breast cancer who took tamoxifen as adjuvant therapy. Methods From June 2014 to June 2016, 84 patients with breast cancer who met the inclusion criteria in the First People′s Hospital of Xiaoshan District were randomly divided into two groups according to the digital table.The treatment group (39 cases) underwent LNG-IUS insertion, while the control group (45 cases) received no LNG-IUS insertion.The general condition of patients before the use of tamoxifen and LNG-IUS was evaluated.Transvaginal ultrasound was used to measure the thickness of endometrium, hysteroscope was used for pathological examination of endometrium and the measurement of ER/PR expression, and blood lipid level was also detected.All above was done before the treatment of tamoxifen and LNG-IUS, 1 year after treatment and 2 years after treatment. Results Before the therapy, there were no statistically significant differences between the two groups in general condition and uterine cavity condition(all P>0.05). After 1 year, the incidences of endometrial polyp, endometrial hyperplasia/secretion, benign lesion and endometrial atrophy in the treatment group were 2.6%, 5.1%, 15.4%, 76.9%, respectively, which in the control group were 6.7%, 20.0%, 17.8%, 55.6%, respectively.the differences between the two groups were statistically significant(χ2=4.06, 4.22, all P<0.05). After 2 years, the incidences of endometrial polyp, endometrial hyperplasia/secretion, benign lesion and endometrial atrophy in the treatment group were 0.0%, 2.6%, 84.6%, respectively, which in the control group were 11.1%, 15.6%, 60.0%, respectively, the differences between the two groups were statistically significant(χ2=4.608, 4.092, 6.203, all P<0.05). Conclusion LNG-IUS can prevent the benign endometrial lesions of breast cancer patients caused by tamoxifen therapy after surgery, and can decrease the incidence of endometrial polyp and endometrial hyperplasia/secretion, while increase the incidence of endometrial atrophy, without increasing the recurrence risk of breast cancer. Key words: Intrauterine devices, Medicated; Levonorgestrel; Tamoxifen; Breast neoplasms; Premenopause; Endometrium

Treatment of symptomatic adenomyosis with the levonorgestrel-releasing intrauterine system.

To determine the long-term effects of using the levonorgestrel-releasing intrauterine system (LNG-IUS) to treat symptomatic adenomyosis. A prospective longitudinal study was conducted among 1100 women who received the LNG-IUS at a tertiary teaching hospital in China between December 10, 2006, and December 24, 2014. All participants had symptomatic adenomyosis (visual analogue scale [VAS] ≥7 and/or pictorial blood loss assessment chart [PBAC] score >100) diagnosed by transvaginal sonography. Follow-up was at 3, 6, 12, 24, 36, 48, and 60months after LNG-IUS placement. The primary outcome was symptom relief. Secondary outcomes included LNG-IUS retention status; changes in uterine volume; serum levels of cancer antigen 125 (CA125); menstruation pattern; and adverse events. In all, 374 (33.7%) participants completed 60months of LNG-IUS treatment. The VAS, verbal rating scale, PBAC score, hemoglobin level, uterine volume, and serum CA125 level all showed marked improvements at this time point when compared with baseline (P<0.05 for all comparisons). The cumulative retention rate of LNG-IUS was 56.2%. Changes in menstruation pattern at 60months included amenorrhea (n=97, 25.9%) and shortened periods (n=82, 21.9%). The incidence of adverse events was <10% and not considered notable. Long-term use of LNG-IUS was effective and acceptable for the treatment of symptomatic adenomyosis. Registered at clinicaltrials.gov (NCT03027648).

The effect of levonorgestrel-releasing intrauterine system on IGF-I and IGF-IR expression after transcervical resection of polyp

Objective To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on insulin-like growth factor-I (IGF-I) and insulin-like growth factor-I receptor (IGF-IR) expression after transcervical resection of polyp (TCRP). Methods 100 cases of endometrial polyps were selected. The control group (n=50) was treated with TCRP only, while the observation group (n=50) was treated with LNG-IUS after TCRP. The scores of pictorial blood loss assessment chart (PBCA), endometrial thickness, recurrence rate, mRNA expression of IGF-I and IGF-IR in endometrial tissue were compared between the two groups. Results At 1, 3, 6, 12 months follow-up, the PBAC score and endometrial thickness of observation group were significantly lower than control group (P<0.05). At 12 months after operation, the mRNA expression levels of IGF-I and IGF-IR in the endometrium of the observation group were significantly lower than those of the control group (P<0.05). After 12 months of follow-up, the recurrence rates of the control group and the observation group were 16.0% (8/50) and 4.0% (2/50), respectively. The recurrence rate of the observation group was significantly lower than that of the control group (P<0.05). Conclusions TCRP combined with LNG-IUS treatment can significantly reduce EP recurrence, and down-regulation of the mRNA expression of IGF-I and IGF-IR maybe its possible mechanism. Key words: Levonorgestrel; Intrauterine devices, medicated; Endometrial polyp; Hysteroscopy; Insulin-like growth factor I; Receptor, IGF type 1

Changes of menstruation patterns and adverse effects during the treatment of LNG-IUS for symptomatic adenomyosis

Objective: To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system(LNG-IUS)for symptomatic adenomyosis in a prospective cohort study. Methods: From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients' parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results: Totally 1 100 cases met inclusion criteria, with median age 36 years(range 20-44 years), median follow-up 35 months(range 1 -108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383)and 29.6%(82/277)patients achieved amenorrhea respectively(P<0.01). Total and subclassification of adverse effects decreased significantly(P<0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P> 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of menstruation patterns or adverse effects neither have any risk factor nor have impact on treatment effects.

A prospective cohort study on the impact of placement timing of LNG-IUS for adenomyosis

To investigate the impact of placement in the procedures of gynecological laparoscopies or routine placement on the effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for symptomatic adenomyosis in a prospective cohort study. From December, 2006 to December, 2014, patients with adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital received the treatment of LNG-IUS.Before and after placement of LNG-IUS all the parameters were recorded including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects.Impact of placement timing (in the procedures of laparoscopies vesus routine placement) on the treatment effects, menstruation patterns and adverse effects of LNG-IUS were analyzed. 1 100 patients meet the inclusion criteria, with median age 36 years (20-44 years), median follow-up 35 months (1-108 months), of which 385 cases (35.0%) received LNG-IUS in the procedures of gynecological laparoscopies. Most common indications and pathology outcomes were endometriosis, major of which had deep infiltrating endometriosis. The accumulative carrying ratio of LNG-IUS were 73% and 63% on 60 months for operative patients and non-operative patients respectively (P<0.001), and accumulative take-out ratio were 7.8% and 10.3% (P=0.044). Placement timing of LNG-IUS was the only significant factor related with loss to follow-up (P<0.001) and take-out ratio (P<0.001). Operations and pathological outcome had no significant impact on patients' treatment effects, changes of menstruation patterns, adverse effects in total or in subclass. Placement of LNG-IUS in the procedures of gynecological laparoscopies for symptomatic adenomyosis increased carrying ratio and reduce take-out ratio at patients'request, but didn't influence treatment effects or adverse effects.

A prospective study on the effects of levonorgestrel-releasing intrauterine system for adenomyosis with menorrhagia

To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with menorrhea in a prospective study. From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients' parameters were recorded prospectively, including scores of menstruation blood loss, carrying status of IUS, symptoms and scores of dysmenorrhea, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Changes of pictorial chart scores of menstruation and distribution of anemia during follow-up were analyzed. Totally 1 100 women meets inclusion criteria, among which 618 cases (56.18%, 618/1 100) had severe menorrhea, with median follow-up period of 28 months (range 1- 60 months), and accumulative carrying rate of 66% at 60 months follow-up. After placement of LNG-IUS, compared with baselines, pictorial chart scores and ratio of menorrhea had decreased significantly (all P<0.01), the scroes of menstruation were 157±34, 94±35, 70±33, 67±18, 67±20, 65±19, 66±19, 65±21 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 24 months after placement of LNG-IUS, pictorial chart scores and distribution of anemia had improved significantly compared with preceding period (all P<0.01). We found no dependent factors predicting improvement of pictorial chart scores of menorrhea, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). LNG-IUS is effective for adenomyosis of menorrhea. Improvement of menstruation blood loss is independent on patients characters, menstruation patterns or adverse effects.

A prospective cohort study on effects of levonorgestrel-releasing intrauterine system for adenomyosis with severe dysmenorrhea

To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with severe dysmenorrhea in a prospective cohort study. From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients' parameters were recorded prospectively, including symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, carrying status of LNG-IUS, menstruation patterns and adverse effects. Changes of scores and patterns of pain during follow-up were analyzed. Totally 1 100 women meets inclusion criteria, among which 640 cases (58.18%, 640/1 100) had severe dysmeorrhea, with median follow-up period of 35 months (range 1-60 months), and accumulative carrying rate of 65% at 60 months follow-up. After placement of LNG-IUS, scores of pain and ratio of severe dysmenorrhea had decreased significantly compared with baselines (all P<0.01), the scroes of visual analog scale (VAS) were 8.1±0.9, 5.5±2.4, 4.6±2.4, 3.3±2.2, 2.2±2.1, 2.2±1.8, 1.4±1.6 and 1.3±1.3 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 36 months after placement of LNG-IUS, scores of pain had improved significantly compared with preceding period (all P<0.01). We found no universal dependent factors predicting improvement of pain, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). LNG-IUS is effective for adenomyosis of severe dysmenorrhea. Improvement of pain is independent on patients characters, menstruation patterns or adverse effects.

Risk of relapse of endometrial hyperplasia is high and long-term treatment and follow up are recommended.

Endometrial hyperplasia can progress to endometrial cancer if left untreated. Hormonal therapies such as the levonorgestrel-releasing intrauterine system (LNG-IUS) and oral progestogens have a role in preventing disease progression. However, once regression of endometrial hyperplasia is achieved the risk of relapse remains. Relapse of endometrial hyperplasia is common and is higher in obese women or those that have been treated with short courses of oral progestogens (Gallos et al. Obstet Gynecol 2013;121:1165–71; Gallos et al. Hum Reprod 2013;28:1231–6). A case–control study with long-term follow up has confirmed that women diagnosed with non-atypical or atypical endometrial hyperplasia are at higher risk of progression to endometrial cancer than women never diagnosed with endometrial hyperplasia (Lacey et al. J Clin Oncol 2010;28:788–92). Moreover, up to 10% of women that relapse will be diagnosed with endometrial cancer at the final hysterectomy specimen (Gallos et al. Hum Reprod 2013;28:1231–6). So can the risk of relapse of endometrial hyperplasia be mitigated? Obesity is the main modifiable risk factor; the risk of relapse is threefold higher for obese women (body mass index > 35 kg/m2) compared with women below this threshold and long-term follow up has been advised for these women (Gallos et al. Obstet Gynecol 2013;121:1165–71). The relapse risk also depends on the type of hormonal therapy used to treat the endometrial hyperplasia. Local intrauterine progestogen should be preferred over other administrative routes to treat endometrial hyperplasia because it is more effective in inducing disease remission (Orbo et al. BJOG 2014;121:477–86). In addition, the risk of relapse is almost three times greater for oral progestogen treatment compared with the LNG-IUS (Gallos et al. Hum Reprod 2013;28:1231–6). However, the LNG-IUS was used for the duration of its licensed use, i.e. 5 years, whereas oral progestogens were restricted in general to courses of up to 6 months. The current randomised study by Orbo et al. (BJOG 2016;123:1512–9.) has demonstrated that the relapse rate is similar in women treated with oral progestogens or the LNG-IUS when both hormonal therapies are limited to 6-month duration. Hence it appears that the increased relapse rate in this current randomised study compared with published observational data is related to the shorter duration of LNG-IUS treatment. From the current trial published in BJOG and the available background observational literature we can infer that the LNG-IUS is preferred for treatment of non-atypical endometrial hyperplasia because it is most effective in reversing the hyperplastic endometrial process and it does reduce the risk of relapse compared with oral progestogen therapy, if used for the full 5-year duration of its licensed use. Obese women should be instructed to normalise their weight to reduce the risk of relapse further. The optimal follow up regimen for women with endometrial hyperplasia not managed by hysterectomy remains to be elucidated. However, women at high risk of relapse or disease progression such as the obese, those refractory to hormonal therapy, those unwilling to receive hormonal or surgical treatment, and those with cytological atypia, should undergo long-term endometrial surveillance. Full disclosure of interests available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or endometrial biopsy. Secondary outcome measures included fibroids, abnormal vaginal bleeding or spotting, breast cancer recurrence, and breast cancer-related deaths. The overall quality of evidence was rated using GRADE methods. Four randomised controlled trials involving 543 women were identified and are included in this review. In the included studies, the active treatment arm was the 20 μg/day levonorgestrel-releasing intrauterine system (LNG-IUS) plus endometrial surveillance; the control arm was endometrial surveillance alone. In tamoxifen users, the LNG-IUS led to a reduction in the incidence of endometrial polyps over both a 12-month period (Peto OR 0.22, 95% CI 0.08 to 0.64, 2 studies, n = 212, I² = 0%) and over a long-term follow-up period (24 to 60 months) (Peto OR 0.22, 95% CI 0.13 to 0.39, 4 studies, n = 417, I² = 0%, moderate quality evidence). Also the LNG-IUS led to a reduction in the incidence of endometrial hyperplasia over a long-term follow-up period (24 to 60 months) (Peto OR 0.13, 95% CI 0.03 to 0.67, four studies, n = 417, I² = 0%, moderate quality evidence). However, it should be noted that the number of events of endometrial hyperplasia was low (n = 6). None of the trials were sufficiently powered to detect whether LNG-IUS leads to significant changes in the incidence of endometrial cancer in tamoxifen users. At 12 months of follow-up abnormal vaginal bleeding or spotting was more common in the LNG-IUS treatment group (Peto OR 7.26, 95% CI 3.37 to 15.66, 3 studies, n = 376, I² = 0%, moderate quality evidence). By 24 months of follow-up, abnormal vaginal bleeding or spotting occurred less frequently compared to 12 months of follow-up in the LNG-IUS treatment group but was still more common than the control group (Peto OR 2.72, 95% CI 1.04 to 7.10, 2 studies, n = 233, I² = 0%, moderate quality evidence). By 60 months of follow-up, no cases of abnormal vaginal bleeding or spotting were reported in either group. The numbers of events for the following outcomes were low: fibroids (n = 13), breast cancer recurrence (n = 18), and breast cancer-related deaths (n = 16). There was no evidence of a difference between the LNG-IUS treatment group and controls for these outcomes. The quality of the evidence was judged as moderate, due to limited sample sizes and low event rates for the outcome comparisons. The LNG-IUS reduces the incidence of benign endometrial polyps and endometrial hyperplasia in women with breast cancer taking tamoxifen. At 12 and 24 months of follow-up, the LNG-IUS increased abnormal vaginal bleeding or spotting among women in the treatment group compared to those in the control. There is no clear evidence from the available randomised controlled trials that the LNG-IUS prevents endometrial cancer in these women. There is no clear evidence from the available randomised controlled trials that the LNG-IUS affects the risk of breast cancer recurrence or breast cancer-related deaths. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and to determine whether the LNG-IUS might have an impact on the risk of secondary breast cancer events.

Levonorgestrel-releasing intrauterine system versus low-dose combined oral contraceptive for treatment of adenomyosis uteri: a randomized clinical trial

Introduction: This study compares the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a low-dose combined oral contraceptive (COC) in reducing adenomyosis-related pain and bleeding. Materials and methods: A randomized clinical trial included 62 participants complaining of pain and bleeding that was associated with adenomyosis. Participants were randomly assigned to either LNG-IUS or COC treatment. The outcomes included the improvement of pain using a visual analogue scale, menstrual blood loss using a menstrual diary and estimated uterine volume by ultrasound for 6 months of treatment. We also compared uterine arteries and intramyometrial Doppler indices before and 6 months after treatment with both LNG-IUS and COCs. Results: Both treatments significantly reduced pain after 6 months of use; however, the reduction was greater in the LNG-IUS group (from 6.23±0.67 to 1.68±1.25) compared with the COCs group (from 6.55±0.68 to 3.90±0.54). Both treatment arms significantly decreased the number of bleeding days, uterine volume and Doppler blood flow in the uterus from before to after treatment. These effects were more significant in the LNG-IUS arm compared with the COC arm. Conclusion: Both LNG-IUS and COCs decreased the pain and menstrual bleeding that is associated with adenomyosis. However, LNG-IUS is more effective than the COCs in reducing pain and menstrual blood loss. This effect may be secondary to the decrease in uterine volume and the increase in blood flow resistance. © 2015 Elsevier Inc. All rights reserved.

Levonorgestrel-releasing intrauterine system versus a low-dose combined oral contraceptive for treatment of adenomyotic uteri: a randomized clinical trial

IntroductionThis study compares the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a low-dose combined oral contraceptive (COC) in reducing adenomyosis-related pain and bleeding. Materials and methodsA randomized clinical trial included 62 participants complaining of pain and bleeding that was associated with adenomyosis. Participants were randomly assigned to either LNG-IUS or COC treatment. The outcomes included the improvement of pain using a visual analogue scale, menstrual blood loss using a menstrual diary and estimated uterine volume by ultrasound for 6 months of treatment. We also compared uterine arteries and intramyometrial Doppler indices before and 6 months after treatment with both LNG-IUS and COCs. ResultsBoth treatments significantly reduced pain after 6 months of use; however, the reduction was greater in the LNG-IUS group (from 6.23±0.67 to 1.68±1.25) compared with the COCs group (from 6.55±0.68 to 3.90±0.54). Both treatment arms significantly decreased the number of bleeding days, uterine volume and Doppler blood flow in the uterus from before to after treatment. These effects were more significant in the LNG-IUS arm compared with the COC arm. ConclusionBoth LNG-IUS and COCs decreased the pain and menstrual bleeding that is associated with adenomyosis. However, LNG-IUS is more effective than the COCs in reducing pain and menstrual blood loss. This effect may be secondary to the decrease in uterine volume and the increase in blood flow resistance.

Cost-effectiveness analysis in the treatment of heavy menstrual bleeding in Spain

ObjectiveTo compare the effectiveness and costs associated with first-line medical treatments for chronic heavy menstrual bleeding (HMB) in Spain. Study designA cost-effectiveness analysis was conducted comparing the levonorgestrel-releasing intrauterine system (LNG-IUS) with the estradiol valerate/dienogest multiphase oral contraceptive (E2V/DNG), combined oral contraceptives (COC) and progestins (PROG). Study patients were fertile women diagnosed with HMB who initially wished to remain fertile. A Markov model based on reported clinical data and the opinion of a panel of experts was used. The time horizon of the analysis was 5 years. The analysis was conducted from the perspective of the Spanish National Health System (NHS), discounting both costs (€ 2013) and future effects at an annual rate of 3%. One-way sensitivity analyses and probabilistic sensitivity analysis were performed to test the robustness of the results. ResultsIn the analysis at 5 years, the LNG-IUS was associated with a gain of 0.67, 2.22, and 3.53 symptoms free months (SFM) compared with E2V/DNG, COC and PROG, respectively. LNG-IUS contributed more quality-adjusted life months (QALM) than the other treatment alternatives (+1.74 vs. E2V/DNG, +3.33 vs. COC +3.53 vs. PROG). First-line LNG-IUS treatment resulted in savings of € 583, € 988, and € 1891 vs. E2V/DNG, COC and PROG, respectively. These cost benefits, coupled with the greater clinical benefits in terms of SFM and QALM, show that LNG-IUS is the dominant option (less costly and more effective). ConclusionLNG-IUS is the medical treatment of choice and cost-saving option for the control of HMB in Spain.