Eeva Lukkari-Lax

Levonorgestrel-Releasing Intrauterine System or Medroxyprogesterone for Heavy Menstrual Bleeding A Randomized Controlled Trial

OBJECTIVE: To compare the efficacy and safety of the levonorgestrel-releasing intrauterine system and oral medroxyprogesterone acetate in the treatment of idiopathic heavy menstrual bleeding. METHODS: In this multicenter, randomized, controlled study, women aged 18 years or older with heavy menstrual bleeding (menstrual blood loss 80 mL or more per cycle) were randomly assigned to six cycles of treatment with either levonorgestrel-releasing intrauterine system or oral medroxyprogesterone acetate (10 mg daily for 10 days beginning on day 16 of each cycle). The primary efficacy variables were the absolute change in menstrual blood loss from baseline to end of study and the proportion of women with successful treatment (defined as menstrual blood loss less than 80 mL and a 50% or greater reduction in menstrual blood loss from baseline). RESULTS: Of 807 women screened, 165 were randomly assigned to treatment (levonorgestrel-releasing intrauterine system n=82, oral medroxyprogesterone acetate n=83). At the end of the study, the absolute reduction in median menstrual blood loss was significantly greater in the levonorgestrel-releasing intrauterine system group (−128.8 mL, range −393.6 to +1242.2 mL) than in the medroxyprogesterone acetate arm (−17.8 mL, range −271.5 to +78.6 mL, P < .001), and the proportion of women with successful treatment was significantly higher for the levonorgestrel-releasing intrauterine system (84.8%) than for medroxyprogesterone acetate (22.2%, P < .001). CONCLUSION: In women with idiopathic heavy menstrual bleeding, the levonorgestrel-releasing intrauterine system reduces menstrual blood loss more effectively and has a higher likelihood of treatment success than oral medroxyprogesterone acetate. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00360490. LEVEL OF EVIDENCE: I

A Phase III, single-arm study of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg) in postmenarcheal adolescents

OBJECTIVE To assess the safety profile of the low-dose levonorgestrel intrauterine system (LNG-IUS) total content 13.5mg (average approximate release rate 8μg/24h over the first year; LNG-IUS 8; Jaydess®) in adolescents. STUDY DESIGN In a Phase III study in 36 European centers, 304 healthy nulliparous or parous postmenarcheal adolescents (12-17years) received LNG-IUS 8 for 12months. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included: serious TEAEs, adverse events of special interest, overall user satisfaction, discontinuation rate at 12months, and Pearl Index. RESULTS LNG-IUS 8 placement was successful in 303/304 participants (99.7%). Overall, 82.6% of participants reported TEAEs, and serious TEAEs and serious study drug-related TEAEs were reported by 7.6% and 1.0% of participants, respectively. No cases of pelvic inflammatory disease, ectopic pregnancy, or uterine perforation were reported. No pregnancies were reported during the 12-month study. At Month 12/study end, the overall user satisfaction rate was 83.9%. Overall, 51 participants (16.8%) prematurely discontinued the study before 12months; 13.8% of participants discontinued owing to TEAEs. CONCLUSIONS No new or unexpected safety events were associated with the low-dose LNG-IUS 8. The safety profile of LNG-IUS 8 in adolescents was consistent with that previously reported in adults. The high overall user-satisfaction rate at study end and the low discontinuation rate over 12months demonstrate that LNG-IUS 8 is a highly acceptable contraceptive method among adolescents. IMPLICATIONS This study is the first to assess the low-dose levonorgestrel intrauterine system LNG-IUS 8 (average approximate release rate 8μg/24h over the first year and total content 13.5mg) specifically in females<18years of age and confirms the safety and efficacy of LNG-IUS 8 in an adolescent population.

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.