Dataset Information

The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial.

ABSTRACT: Two low-dose levonorgestrel intrauterine contraceptive systems (LNG-IUSs; total content 13.5 mg [average approx. 8 ?g/24 hours over the first year; LNG-IUS 8] and total content 19.5 mg [average approx. 13 ?g/24 hours over the first year; LNG-IUS 13]) have previously been shown to be highly effective (3-year Pearl Indices: 0.33 and 0.31, respectively), safe and well tolerated. The present subgroup analyses evaluated whether or not outcomes were affected by parity, age (18-25 vs 26-35 years), or body mass index (BMI, <30 vs ?30 kg/m2).Nulliparous and parous women aged 18?35 years with regular menstrual cycles (21?35 days) requesting contraception were randomized to 3 years of LNG-IUS 8 or LNG-IUS 13 use.In the LNG-IUS 8 and LNG-IUS 13 groups, 1432 and 1452 women, respectively, had a placement attempted and were included in the full analysis set; 39.2%, 39.2% and 17.1% were 18-25 years old, nulliparous and had a BMI ?30 kg/m2, respectively. Both systems were similarly effective regardless of age, parity or BMI; the subgroup Pearl Indices had widely overlapping 95% confidence intervals. Placement of LNG-IUS 8 and LNG-IUS 13 was easier (p < 0.0001) and less painful (p < 0.0001) in women who had delivered vaginally than in women who had not. The complete/partial expulsion rate was 2.2-4.2% across all age and parity subgroups and higher in parous than in nulliparous women (p = 0.004). The incidence of pelvic inflammatory disease was 0.1-0.6% across all age and parity subgroups: nulliparous and younger women were not at higher risk than parous and older women, respectively. The ectopic pregnancy rate was 0.3-0.4% across all age and parity subgroups. Across all age and parity subgroups, the 3-year completion rate was 50.9-61.3% for LNG-IUS 8 and 57.9-61.1% for LNG-IUS 13, and was higher (p = 0.0001) among older than younger women in the LNG-IUS 8 group only.LNG-IUS 8 and LNG-IUS 13 were highly effective, safe and well tolerated regardless of age or parity.Clinical trials.gov NCT00528112.

SUBMITTER: Gemzell-Danielsson K

PROVIDER: S-EPMC4574776 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial.

Gemzell-Danielsson Kristina K Apter Dan D Hauck Brian B Schmelter Thomas T Rybowski Sarah S Rosen Kimberly K Nelson Anita A

PloS one 20150917 9

<h4>Objective</h4>Two low-dose levonorgestrel intrauterine contraceptive systems (LNG-IUSs; total content 13.5 mg [average approx. 8 μg/24 hours over the first year; LNG-IUS 8] and total content 19.5 mg [average approx. 13 μg/24 hours over the first year; LNG-IUS 13]) have previously been shown to be highly effective (3-year Pearl Indices: 0.33 and 0.31, respectively), safe and well tolerated. The present subgroup analyses evaluated whether or not outcomes were affected by parity, age (18-25 vs ...[more]

PMID: 26378938

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Project description:Study questionWhat is the bleeding pattern during second consecutive levonorgestrel-releasing intrauterine system (LNG-IUS) use?Summary answerConsecutive use of LNG-IUS is associated with a predictable bleeding pattern, characterized by the absence of the initial period of irregular bleeding seen after interval insertion of an LNG-IUS and a non-bleeding pattern in the vast majority of women.What is known alreadyWith increased popularity of the LNG-IUS for long-term birth control and treatment of heavy menstrual bleeding (HMB), consecutive use of the system is becoming more frequent. One previous study showed 60% amenorrhea rate in consecutive IUS users; however, the sample size was small.Study design, size, durationA prospective multicenter study in four European countries recruited women who wished to continue with LNG-IUS use immediately after the first 5-year period. A total of 204 women were followed up until the end of the first year of the second IUS. Thereafter 170 women continued into the extension phase of the study up to the full 5 years of use of the second IUS and 144 women continued to the end of the study.Participants, setting, methodsA total of 170 women (mean age 39 years) who had been using their first LNG-IUS for between 4 years 3 months and 4 years 9 months, either for contraception or for treatment of HMB, and who planned to replace the device with a new LNG-IUS, were recruited and followed up to 5 years of the second IUS use. A total of 17 centers in four European countries were involved in the study. Bleeding patterns were analyzed using daily bleeding diaries using 90-day reference periods (RP) for the first year of the second IUS use and for the last RP of each year during Years 2-5 of use.Main results and the role of chanceApproximately 70% of women were free of bleeding during Years 2-5 and up to 49% were amenorrheic. There was a slight increase in the number of bleeding/spotting days of ∼3 days during the first RP immediately after the placement of the second IUS, whereafter the number of bleeding/spotting days returned to the level preceding the second IUS insertion or below that. Absence of bleeding was associated with high overall satisfaction and continuation rates. No serious adverse events assessed as related to the LNG-IUS use occurred during the 5-year period. The cumulative expulsion rate during the 5-year study period was 1.2%. The sample size was large enough to study bleeding patterns, and subjects are likely to represent typical consecutive IUS users, and therefore, the role of chance is small.Limitations, reasons for cautionThe women represent a selected group as they had already successfully used their first IUS for almost 5 years and were willing to continue its use-however, this is currently a common clinical situation. The results may therefore not be extrapolated to first-time users of the LNG-IUS.Wider implications of the findingsThese data are of importance when counseling women who are making decisions concerning long-term contraception.Study funding/competing interest(s)This study was funded by Bayer Pharma AG. P.I. and T.S. are full-time employees of Bayer Pharma AG. O.H. and K. G-D. have received consultancy fees from Bayer Pharma AG. The publication was developed jointly by all authors without third-party involvement and no honoraria were paid for any authors for their contribution to this manuscript.Trial registration numberNCT00393198.

Project description:The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.

Project description:OBJECTIVE:To assess the 5-year contraceptive efficacy and safety of a levonorgestrel (LNG) 52-mg intrauterine system (IUS) from an ongoing 10-year phase 3 contraceptive trial. METHODS:Study investigators enrolled 1,751 nulliparous and parous females aged 16-45 years and desiring contraception to receive a novel LNG 52-mg IUS at 29 centers in the United States, including reproductive health clinics, private offices, and university centers. Participants had scheduled follow-up visits four times during the first year. After year 1, study visits occurred every 6 months, with phone contact at the 3-month point between visits. We assessed the primary outcome of pregnancy rate (Pearl Index) in females aged 16-35 years at enrollment through 60 months. The safety evaluation included all females for their entire duration of participation. RESULTS:The 1,751 enrollees included 1,600 females aged 16-35 years and 151 aged 36-45 years. Successful IUS placement occurred in 1,714 (97.9%) participants. At the time of the data evaluation, 495 participants finished 5 years and 176 had entered the seventh year of IUS use. Nine pregnancies occurred, six of which were ectopic. The Pearl Indices for years 1 and 5 were 0.15 (95% CI 0.02-0.55) and 0.20 (95% CI 0.01-1.13) pregnancies per 100 women-years, respectively. The cumulative life-table pregnancy rate was 0.92% (0.46-1.82%) through 5 years. Participants aged 16-35 years at enrollment were significantly more likely to report new or worsening acne, dyspareunia, pelvic pain, and dysmenorrhea; participants aged 36-45 years at enrollment were more likely to report new or worsening weight increase. Discontinuation for adverse events occurred in 322 (18.8%) participants, most commonly related to expulsion (n=65 [3.8%]). Only 39 (2.2%) IUS users discontinued as a result of bleeding symptoms. Pelvic infection was diagnosed in 14 (0.8%) participants. CONCLUSION:This LNG 52-mg IUS is highly effective and safe over 5 years of use in U.S. females. CLINICAL TRIAL REGISTRATION:Clinicaltrials.gov, NCT00995150. FUNDING SOURCE:Medicines360.

Dataset Information

The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial.

Publications

The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial.

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