Therapy of heavy menstrual bleeding in Korea: Subanalysis and results from a multinational clinical trial in the Asian region investigating the levonorgestrel-releasing intrauterine system versus conventional therapy.

OBJECTIVE: To compare real-life clinical outcomes with the levonorgestrel-releasing intrauterine system (LNG-IUS) and conventional medical therapies (CMTs), including combined oral contraceptives and oral progestins in the treatment of idiopathic heavy menstrual bleeding (HMB) in South Korea. METHODS: This prospective, observational cohort study recruited a total of 647 women aged 18 to 45 years, diagnosed with HMB from 8 countries in Asia, including 209 women from South Korea (LNG-IUS, 169; CMTs, 40), who were followed up to one year. The primary outcome was cumulative continuation rate (still treated with LNG-IUS and CMTs) at 12 months. Secondary outcomes included bleeding pattern, assessment of the treatment efficacy by treating physician and safety profile. RESULTS: The continuation rate at 12 months was significantly higher with the LNG-IUS than CMTs (85.1% vs. 48.5%, respectively; P<0.0001). The 51.5% of CMTs patients discontinued treatment and 18.8% of LNG-IUS patients discontinued treatment. The most common reasons for discontinuation for CMTs were switching to another treatment and personal reasons. When compared to CMTs, the LNG-IUS offered better reduction in subjectively assessed menstrual blood loss and the number of bleeding days, tolerability and with better efficacy in HMB, as assessed by physician's final evaluation. CONCLUSION: This study provides novel information on the real-life treatment patterns of HMB in South Korea. The efficacy of CMTs was inferior compared to the LNG-IUS in the clinical outcomes measured in this study. Due to the better compliance with LNG-IUS, the cumulative continuation rate is higher than CMTs. We conclude that the LNG-IUS should be used as the first-line treatment for HMB in Korean women, in line with international guidelines.

Satisfaction and health-related quality of life in women with heavy menstrual bleeding; results from a non-interventional trial of the levonorgestrel-releasing intrauterine system or conventional medical therapy.

PURPOSE: To evaluate the patient satisfaction and health related quality of life (HRQoL) for levonorgestrel-releasing intrauterine system (LNG-IUS) versus conventional medical treatments ([CMTs] combined oral contraceptives, oral progestins, and antifibrinolytics, alone or in combination) in Asian women with heavy menstrual bleeding (HMB). PATIENTS AND METHODS: A total of 647 patients diagnosed with HMB were recruited to this non-interventional study from the eight participating countries in Asia. Patient satisfaction was recorded at the last visit (at 12 months or premature discontinuation). At each visit (at 3, 6, and 12 months), patients completed the menorrhagia multi-attribute scale (MMAS) to assess HRQoL. RESULTS: A total of 83.5% of patients on the LNG-IUS were "very satisfied" or at least "satisfied" with the therapeutic effect of HMB treatment, compared with 59.2% of patients with CMTs (P<0.05). The mean (± standard deviation) MMAS score increased from 41.4±24.5 to 87.7±21.4 in the LNG-IUS arm, and from 44.1±24.9 to 73.1±25.3 in the CMTs arm. This increase was significantly higher in patients on the LNG-IUS, as compared with those on CMTs (P<0.05). The improvement in HRQoL in both treatment groups correlated with the body mass index of the patient, with larger improvement obtained in women with a higher body mass index. CONCLUSION: The majority of women using the LNG-IUS or CMTs for HMB were satisfied with their treatment, and both treatment modalities were associated with significant improvements in HRQoL over time. The improvement was greater with the LNG-IUS, compared with CMTs.

Acceptability of long-acting, progestin-only contraception in Europe: a two-year prospective, non-interventional study.

OBJECTIVES To compare two-year continuation rates and user satisfaction with the levonorgestrel releasing-intrauterine system (LNG-IUS) and the etonogestrel releasing-subdermal implant (ENG implant) in women in Europe. METHODS This prospective, non-interventional study was undertaken at 72 sites in France (n = 61), Great Britain (n = 2), Ireland (n = 3) and Slovakia (n = 6). Women opting to switch their method of contraception to the LNG-IUS or the ENG implant were followed-up over 24 months to document continuation and satisfaction with their chosen contraceptive method. Reasons for discontinuation were documented. RESULTS The data analysed were based on 363 women (LNG-IUS [n = 247] and ENG implant [n = 116]), aged 20 to 45 years, with at least one follow-up visit after contraceptive placement. The documented cumulative continuation rate was 82% in the LNG-IUS group and 67% in the ENG implant group at 24 months. The documented discontinuation rates were 13% and 17%, respectively. Bleeding problems were cited as reason for discontinuation in 4% and 11% of women in the LNG-IUS and ENG implant groups, respectively. CONCLUSIONS The LNG-IUS is associated with higher continuation rates and user satisfaction than the ENG implant in this study of women in Europe, though the groups were not similar in all respects. Bleeding problems with the ENG implant account for most of the reasons for discontinuing its use.

Management of initial bleeding or spotting after levonorgestrel-releasing intrauterine system placement: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of tranexamic acid or mefenamic acid in the management of the initial "nuisance" bleeding or spotting in the period immediately after placement of the levonorgestrel-releasing intrauterine system. METHODS: Women were randomized after levonorgestrel-releasing intrauterine system placement to oral tranexamic acid (500 mg), mefenamic acid (500 mg), or placebo three times daily during bleeding or spotting episodes over a 90-day treatment period. Treatment was initiated from onset of a bleeding or spotting episode and continued until the first day after bleeding or spotting stopped and restarted with a new bleeding or spotting episode. The primary efficacy variable was reduction in the number of bleeding or spotting days. Tranexamic acid and mefenamic acid were compared with placebo using a one-sided Wilcoxon rank-sum test. Bonferroni-Holm adjustment was used to account for multiple testing. RESULTS: A total of 204 women were screened; 187 were randomized to tranexamic acid (n=63), mefenamic acid (n=63), or placebo (n=61). The median number of bleeding or spotting days experienced during treatment was 25, 29, and 33 days in the three groups, respectively. The median number of bleeding or spotting days was reduced by 6 days (95% confidence interval [CI] -14.0 to 1.0, P=.049) with tranexamic acid and by 3 days (95% CI -11.0 to 5.0, P=.229) with mefenamic acid compared with placebo. The relative risk of bleeding or spotting compared with placebo with tranexamic acid and mefenamic acid was 0.82 (95% CI 0.65-1.03) and 0.89 (95% CI 0.71-1.11), respectively. Most women (85% or more) were satisfied with the levonorgestrel-releasing intrauterine system across the groups. CONCLUSIONS: Tranexamic acid and mefenamic acid during the first 90 days after levonorgestrel-releasing intrauterine system placement do not alleviate "nuisance" bleeding or spotting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01295294. LEVEL OF EVIDENCE: I.

Levonorgestrel-releasing intrauterine system versus conventional medical therapy for heavy menstrual bleeding in the Asia-Pacific region.

OBJECTIVE: To compare clinical outcomes, including cumulative continuation rate (CCR), in the treatment of idiopathic heavy menstrual bleeding (HMB) with the levonorgestrel-releasing intrauterine system (LNG-IUS) and with conventional medical therapies (CMTs), including combined oral contraceptives, oral progestins, and antifibrinolytics, either alone or in combination, in the Asia-Pacific region. METHODS: In a prospective observational cohort study conducted between September 2008 and December 2010, 647 women (LNG-IUS, n=483; CMTs, n=164), aged 18-45 years and diagnosed with HMB, were recruited from 8 countries and followed for up to 1 year. The primary outcome was the CCR at 12 months. Secondary outcomes included bleeding pattern, an assessment of treatment efficacy by the treating physician, and safety. RESULTS: The CCR at 12 months was significantly higher for LNG-IUS than for CMTs (87.6% vs 56.3% P<0.05). Compared with CMTs, LNG-IUS offered a better reduction in both subjectively assessed menstrual blood loss and the number of bleeding days, and had better efficacy for HMB, as determined by the physician's final evaluation. CONCLUSION: The present study provides information on the real-life patterns of treatment of HMB in the Asia-Pacific region. The efficacy of CMTs was inferior compared with LNG-IUS in the clinical outcomes measured. ClinicalTrials.gov:NCT00864136.

Bleeding patterns with the levonorgestrel-releasing intrauterine system when used for heavy menstrual bleeding in women without structural pelvic pathology: a pooled analysis of randomized controlled studies.

BACKGROUND: The study was conducted to characterize the changes in bleeding pattern over time in women receiving the levonorgestrel-releasing intrauterine system (LNG-IUS) for heavy menstrual bleeding (HMB). The reduction in menstrual blood loss volume has been well documented elsewhere. STUDY DESIGN: Post hoc pooled analysis of the impact of the LNG-IUS on bleeding patterns in four comparator studies of medical and surgical treatment options for HMB. We enrolled women aged ≥18 years with HMB without organic pathology. The change in the number of bleeding and spotting (B/S) days and bleeding patterns was assessed over the duration of the studies pooled. RESULTS: One hundred and sixty-three women received the LNG-IUS in randomized trials. Relative to pretreatment baseline, there was a transient increase in the mean number of bleeding days in the first month of treatment, which returned to baseline by the second month and declined thereafter. Although the number of spotting days also increased during the first month of treatment, these declined with continued use but remained elevated relative to baseline during the first year of treatment. CONCLUSION: In women with HMB, the LNG-IUS is associated with an initial increase in number of B/S days that improve over time.

Use of contraceptive methods and contraceptive recommendations among health care providers actively involved in contraceptive counseling -- results of an international survey in 10 countries.

BACKGROUND: This study was conducted to determine the personal choices of contraceptive methods among an international sample of contraception health care professionals (HCPs) and to determine if these choices are concordant with their recommendations to women. STUDY DESIGN: In an anonymous online survey, 1001 HCPs actively involved in contraceptive counseling [obstetrician/gynecologists (OB/GYNs), general practitioners (GPs) and midwives (only in Sweden)] from 10 countries (Australia, Brazil, Canada, France, Germany, Korea, Mexico, Spain, Sweden and the United Kingdom) were asked about their personal use of contraceptive methods and their recommendations to women in two different clinical scenarios: for spacing between children (Group A) and after completion of the family (Group B). RESULTS: The largest HCP group was OB/GYNs (67.1%), followed by GPs (31.4%) and midwives (1.5%). A total of 42.7% of respondents were male, and 57.3% were female. The majority of respondents were aged 36-45 years (38.9%) or 46-55 years (42.8%), 79.7% had children, and 53.9% were currently using contraception (by themselves or by their partners). Among 540 contraceptive users, the three most common methods were the levonorgestrel-releasing intrauterine system (LNG-IUS; 29.3%), combined oral contraceptives (COCs; 20.0%) and condoms (17.0%). OB/GYNs were more likely to be using the LNG-IUS than GPs (p=.014). Gender did not seem to influence contraceptive preference. Reasons for these choices were largely influenced by family situation and high contraceptive efficacy (for the LNG-IUS) or side effects caused by other methods (for condoms). The top contraceptive recommendation was COCs for Group A and the LNG-IUS for Group B. HCPs currently using COCs and the LNG-IUS were more likely to recommend these methods than other contraceptive methods for Group A and Group B, respectively. CONCLUSIONS: The most popular contraceptive method in this sample of HCPs was the LNG-IUS. Choice of contraceptive method was driven by family situation, age and profession. It appears that, in this sample, personal contraceptive use influences contraceptive recommendations.

The levonorgestrel-releasing intrauterine system in heavy menstrual bleeding: a benefit-risk review.

Heavy menstrual bleeding (HMB) is a common problem in women of reproductive age and can cause irritation, inconvenience, self-consciousness and fear of social embarrassment. Our objective was to review and appraise literature identified from the MEDLINE and EMBASE databases to evaluate the clinical evidence and provide an update on the risks and benefits of using the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of HMB. The LNG-IUS consistently reduces menstrual blood loss (MBL) in women with HMB, including those with underlying uterine pathology or bleeding disorders. The available data suggest that it reduces MBL to a greater extent than other medical therapies, including combined oral contraceptives, oral progestogens (both short- or long-cycle regimens), tranexamic acid and oral mefenamic acid. In addition, the LNG-IUS and endometrial ablation appear to reduce MBL to a similar extent. The adverse effects reported with the LNG-IUS in women with HMB are similar to those typically observed in women using the system for contraception. Uterine perforations were not reported in any of the studies reviewed, but expulsion rates may be higher than in the general population of LNG-IUS users. Overall, the LNG-IUS has a positive effect on most quality-of-life domains, at least comparable to those achieved with hysterectomy or endometrial ablation, and is consistently a cost-effective option across a variety of countries and settings. In conclusion, the LNG-IUS is an effective treatment option for women with HMB, including those with underlying organic pathology or bleeding disorders.

Acceptability of the levonorgestrel releasing-intrauterine system and etonogestrel implant: one-year results of an observational study.

OBJECTIVES: To analyse the acceptability and patterns of use of the levonorgestrel releasing-intrauterine system (LNG-IUS) and the etonogestrel releasing-subdermal implant (ENG implant) among young European women. METHODS: A total of 454 women aged 20-35 years opting to switch their method of contraception from oral contraception to the LNG-IUS or ENG implant, were recruited in an observational study in four different European countries (France, Ireland, Slovakia and the United Kingdom). The present paper reports the interim results of the study at 12 months of observation. RESULTS: Data from 311 subjects (211 using the LNG-IUS and 100 using the ENG implant), with at least one follow-up visit after insertion, were analysed. The cumulative continuation rates at 12 months for the LNG-IUS and ENG implant were 93% and 86%, respectively. Most women were satisfied with their method of contraception after one year of follow-up (80% in the LNG-IUS group and 66% in the ENG implant group). CONCLUSIONS: Both the LNG-IUS and the ENG implant are highly acceptable contraceptive options among women with previous experience of oral contraceptive use. The highest continuation and satisfaction rates were observed with the LNG-IUS.

Fertility after discontinuation of contraception: a comprehensive review of the literature.

BACKGROUND: Fear of adverse effects on subsequent fertility following reversible contraceptive use is an important concern for some women. STUDY DESIGN: We undertook a comprehensive and objective review of the literature for prospective studies reporting pregnancy rates in women following contraceptive cessation. One-year pregnancy rates and pregnancy outcomes are summarized. RESULTS: We identified and analyzed 17 studies according to preset criteria. Typical 1-year pregnancy rates following cessation of oral contraceptives or the levonorgestrel-releasing intrauterine system (LNG-IUS) ranged between about 79% and 96% and those for copper intrauterine devices (IUDs) were almost as high, ranging between about 71% and 91%. One-year pregnancy rates following cessation of contraceptive implants were between 77% and 86%, with one study showing a rate lower than 50%. For injectable contraceptives [(a) norethisterone enanthate and (b) 5 mg estradiol cypionate and 25 mg medroxyprogesterone (Cyclofem)], only two studies were reported, with 1-year pregnancy rates following cessation of 73% and 83%, respectively. There was no evidence of increased pregnancy complications or adverse fetal outcomes following cessation of any of the reversible methods reported. CONCLUSIONS: Overall, 1-year pregnancy rates following cessation of oral contraceptives, contraceptive implants and monthly injections, copper IUDs and the LNG-IUS are broadly similar to those reported following discontinuation of barrier methods or use of no contraceptive method.

Recent developments in the clinical use of the levonorgestrel-releasing intrauterine system.

This overview focuses on recent developments in the clinical use of the levonorgestrel- releasing intrauterine system (LNG-IUS) on established indications. Recent studies confirm that the LNG-IUS is safe and equally effective for all age groups of women. All available studies showed that intrauterine contraception is more effective when compared to non-intrauterine contraceptive methods to prevent repeat abortions. Furthermore, insertion in young nulliparous women is acceptable in the majority of women and associated with high continuation rates. The effectivity of LNG-IUS appears to be similar in women with chronic medical conditions, including HIV infection or coagulation disorders, and healthy women. More and most importantly, it has no adverse effect on the underlying condition. We also discuss effects of LNG-IUS on bone mineral density, vaginal flora, cardiovascular risk factors and breast cancer. In treatment of heavy menstrual bleeding, the LNG-IUS appears to be one of the most effective and cost-effective methods.

Efficacy of contraceptive methods: a review of the literature.

OBJECTIVES: To provide a comprehensive and objective summary of contraceptive failure rates for a variety of methods based on a systematic review of the literature. METHODS: Medline and Embase were searched using the Ovid interface from January 1990 to February 2008, as well as the reference lists of published articles, to identify studies reporting contraceptive efficacy as a Pearl Index or life-table estimate. Reports that recruited less than 400 subjects per study group and those covering less than six cycles/six months were excluded. In addition, unlicensed products or those not internationally available, emergency contraception, and vasectomy studies were excluded. RESULTS: Information was identified and extracted from 139 studies. One-year Pearl Indices reported for short-acting user-dependent hormonal methods were generally less than 2.5. Gross life-table rates for long-acting hormonal methods (implants and the levonorgestrel releasing-intrauterine system [LNG-IUS]) generally ranged between 0-0.6 per 100 at one year, but wider ranges (0.1-1.5 per 100) were observed for the copper intrauterine devices (0.1-1.4 per 100 for Cu-UIDs with surface area ≥ 300 mm2 and 0.6-1.5 per 100 for those with surface area < 300 mm2). Barrier and natural methods were the least effective. CONCLUSIONS: Our review broadly confirms the hierarchy of contraceptive effectiveness in descending order as: (1) female sterilisation, long-acting hormonal contraceptives (LNG-IUS and implants); (2) Cu-IUDs with ≥ 300 mm2 surface area; (3) Cu-IUDs with < 300 mm2 surface area and short-acting hormonal contraceptives ( injectables, oral contraceptives, the patch and vaginal rings), (4) barrier methods and natural methods.

Double-blind, randomized, placebo-controlled study on the effect of misoprostol on ease of consecutive insertion of the levonorgestrel-releasing intrauterine system.

BACKGROUND: Misoprostol has been studied intensively to produce cervical dilatation. To date, no studies have evaluated the effectiveness, safety or acceptability of this treatment for repeat intrauterine device insertions. STUDY DESIGN: This study was a randomized, double-blind, placebo-controlled trial on the consecutive use of the levonorgestrel-releasing intrauterine system (LNG-IUS). Women who had used their first LNG-IUS for 4 years and 3 to 9 months and opted for an immediate replacement with a second LNG-IUS received a single sublingual dose of 400 mcg misoprostol or placebo 3 h prior to the LNG-IUS insertion. RESULTS: The proportion of easy insertions as judged by the investigator was 93% (40/43) in subjects randomized to misoprostol and 91% (42/46) in the placebo group (p=1.0 for the difference of proportions). No or mild pain at insertion was reported by 37% and 35% of subjects in the misoprostol and placebo groups, respectively. However, adverse events related to the study drug were more common in the misoprostol group. CONCLUSION: Sublingual misoprostol did not have a significant effect on the ease of insertion in subjects having a repeat insertion of the LNG-IUS.

Efficacy of contraceptive methods: A review of the literature.

OBJECTIVES: To provide a comprehensive and objective summary of contraceptive failure rates for a variety of methods based on a systematic review of the literature. METHODS: Medline and Embase were searched using the Ovid interface from January 1990 to February 2008, as well as the reference lists of published articles, to identify studies reporting contraceptive efficacy as a Pearl Index or life-table estimate. Reports that recruited less than 400 subjects per study group and those covering less than six cycles/six months were excluded. In addition, unlicensed products or those not internationally available, emergency contraception, and vasectomy studies were excluded. RESULTS: Information was identified and extracted from 139 studies. One-year Pearl Indices reported for short-acting user-dependent hormonal methods were generally less than 2.5. Gross life-table rates for long-acting hormonal methods (implants and the levonorgestrel releasing-intrauterine system [LNG-IUS]) generally ranged between 0-0.6 per 100 at one year, but wider ranges (0.1-1.5 per 100) were observed for the copper intrauterine devices (0.1-1.4 per 100 for Cu-IUDs with surface area > or =300 mm( 2 ) and 0.6-1.5 per 100 for those with surface area <300 mm( 2 )). Barrier and natural methods were the least effective. CONCLUSIONS: Our review broadly confirms the hierarchy of contraceptive effectiveness in descending order as: (1) female sterilisation, long-acting hormonal contraceptives (LNG-IUS and implants); (2) Cu-IUDs with > or =300 mm( 2 ) surface area; (3) Cu-IUDs with <300 mm( 2 ) surface area and short-acting hormonal contraceptives (injectables, oral contraceptives, the patch and vaginal ring), and (4) barrier methods and natural methods.

Levonorgestrel-releasing intrauterine system and endometrial ablation in heavy menstrual bleeding: a systematic review and meta-analysis.

OBJECTIVE: To compare the effects of the levonorgestrel intrauterine system and endometrial ablation in reducing heavy menstrual bleeding. DATA SOURCES: Medline and EMBASE were searched online using Ovid up to January 2009, as well as the reference lists of published articles, to identify randomized controlled trials comparing the levonorgestrel intrauterine system with endometrial ablation in the treatment of heavy menstrual bleeding. METHODS OF STUDY SELECTION: This systematic review and meta-analysis was restricted to randomized controlled trials in which menstrual blood loss was reported using pictorial blood loss assessment chart scores. TABULATION, INTEGRATION, AND RESULTS: Six randomized controlled trials that included 390 women (levonorgestrel intrauterine system, n=196; endometrial ablation, n=194) were retrieved. Three studies pertained to first-generation endometrial ablation (manual hysteroscopy) and three to second-generation endometrial ablation (thermal balloon). Study characteristics and quality were recorded for each study. Data on the effect of treatment on pictorial blood loss assessment chart scores were abstracted, integrated with meta-analysis techniques, and presented as weighted mean differences. Both treatment modalities were associated with similar reductions in menstrual blood loss after 6 months (weighted mean difference, -31.96 pictorial blood loss assessment chart score [95% confidence interval (CI), -65.96 to 2.04]), 12 months (weighted mean difference, 7.45 pictorial blood loss assessment chart score [95% CI, -12.37 to 27.26]), and 24 months (weighted mean difference, -26.70 pictorial blood loss assessment chart score [95% CI, -78.54 to 25.15]). In addition, both treatments were generally associated with similar improvements in quality of life in five studies that reported this as an outcome. No major complications occurred with either treatment modality in these small trials. CONCLUSION: Based on the meta-analysis of six randomized clinical trials, the efficacy of the levonorgestrel intrauterine system in the management of heavy menstrual bleeding appears to have similar therapeutic effects to that of endometrial ablation up to 2 years after treatment.

Long-term use of the levonorgestrel-releasing intrauterine system.

Since its launch in Finland in 1990, the levonorgestrel-releasing intrauterine system (LNG IUS) has become available in more than 100 countries throughout the world, with most countries also having the approval for the treatment of idiopathic menorrhagia and protection from endometrial hyperplasia during estrogen replacement therapy. After its introduction in Finland and Scandinavian countries, the LNG IUS has been available in most European countries since the mid to late 1990s and in the United States since 2001. Studies on the repeat use of the LNG IUS with second and third consecutive IUSs have shown high continuation rates and low rates of adverse effects. During repeat use of the LNG IUS, the bleeding pattern changes toward an increasing amenorrhea rate. With regard to the menorrhagia indication, the 5-year follow-up results of a randomized comparative trial of the LNG IUS and hysterectomy have shown equal satisfaction and improvement in health-related quality of life with both treatments. Although a proportion of women assigned to the LNG IUS group eventually underwent hysterectomy, the continuation rate of the LNG IUS for menorrhagia is clearly superior to that of conventional medical therapy (e.g., oral progestins). Use of the LNG IUS in combination with estrogen therapy in women undergoing menopausal transition seems to be well tolerated and associated with a favorable bleeding pattern.

Use of the levonorgestrel-releasing intrauterine system and breast cancer.

OBJECTIVE: The effect of exogenous hormones on the incidence of breast cancer has been extensively studied. Most studies regarding hormonal contraception have focused on combined oral contraceptives, and there is paucity of literature regarding nonoral and progestin-only contraceptives. The present study analyzed the relationship between breast cancer and use of the levonorgestrel-releasing intrauterine system. METHODS: This study was based on data gathered from a large postmarketing study on levonorgestrel-releasing intrauterine system users (n = 17,360) carried out in Finland. The results present an incidence comparison between levonorgestrel system user data and the data on average Finnish female population (derived from the Finnish Cancer Registry), between 30 and 54 years of age. RESULTS: Based on the 95% confidence intervals for the incidences of breast cancer, and the Fisher exact test, there is no indication of a difference between the levonorgestrel system users and average Finnish female population in any of the 5-year age groups. The incidence rate per 100,000 woman-years was for the age groups 30-34 years 27.2 and 25.5, for 35-39 years 74.0 and 49.2, for 40-44 years 120.3 and 122.4, for 45-49 years 203.6 and 232.5, and for 50-54 years 258.5 and 272.6, in the levonorgestrel system group and in Finnish female population, respectively. CONCLUSION: The results suggest that the use of the levonorgestrel-releasing intrauterine system is not associated with an increased risk of breast cancer.