Safety and continued use of the levonorgestrel intrauterine system as compared with the copper intrauterine device among women living with HIV in South Africa: A randomized controlled trial.
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ABSTRACT:
SUBMITTER: Todd CS
PROVIDER: S-EPMC7244096 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Safety and continued use of the levonorgestrel intrauterine system as compared with the copper intrauterine device among women living with HIV in South Africa: A randomized controlled trial.
Todd Catherine S CS Jones Heidi E HE Langwenya Nontokozo N Hoover Donald R DR Chen Pai-Lien PL Petro Gregory G Myer Landon L
PLoS medicine 20200522 5
<h4>Background</h4>Women living with HIV (WLHIV) have lower rates of contraceptive use than noninfected peers, yet concerns regarding contraceptive efficacy and interaction with antiretroviral therapy (ART) complicate counseling. Hormonal contraceptives may increase genital tract HIV viral load (gVL) and sexual transmission risk to male partners. We compared gVL, plasma VL (pVL), and intrauterine contraceptive (IUC) continuation between the levonorgestrel intrauterine system (LNG-IUS) and copper ...[more]
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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.
2020-04-29 | GSE137765 | GEO
Project description:BackgroundGlobally, approximately 19.4% of women of reproductive age use intrauterine contraception, encompassing both copper intrauterine devices (Cu-IUDs) and levonorgestrel intrauterine devices (LNG-IUDs). Despite current guidelines endorsing intrauterine contraception as a primary method, there remains debate regarding device selection. Notably, the lack of data regarding reasons for discontinuation has limited previous meta-analyses. This study aims to comprehensively evaluate the potential differences between intrauterine devices using available multinational data, thereby providing a basis for global policy and healthcare services.MethodsWe systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library for primary studies published from inception to January 13, 2024, with no language or geographic restrictions. The study was registered on PROSPERO (CRD42024496400). We included only randomized controlled trials comparing Cu-IUDs and LNG-IUDs. Data extraction was independently conducted by two reviewers, with unresolved discrepancies referred to a third senior reviewer for consultation. The primary outcome was pregnancy, with secondary outcomes encompassing continuation, reasons for discontinuation, expulsion, satisfaction, and other adverse events. Data were synthesized using a random-effects model. Risk of bias was evaluated with the Cochrane Collaboration's tool, and evidence quality was assessed using the GRADE framework.FindingsAn analysis of 20 trials showed that compared to Cu-IUDs, LNG-IUDs were associated with lower risks of pregnancy (Risk Ratio 0.22, 95% confidence interval 0.12-0.39), ectopic pregnancy (RR 0.12, 95% CI 0.03-0.47), discontinuation due to increased bleeding (RR 0.49, 95% CI 0.28-0.85), increased bleeding (RR 0.42, 95% CI 0.25-0.7), heavy bleeding (RR 0.41, 95% CI 0.22-0.75), and dysmenorrhea (RR 0.41, 95% CI 0.34-0.48), but they carried a higher risk of discontinuation due to amenorrhea (RR 21.05, 95% CI 8.83-50.00). When comparing LNG (52 mg) IUD with copper (380 mm2) IUD, The LNG-IUD showed a lower risk of discontinuation due to increased bleeding (RR 0.68, 95% CI 0.55-0.58) and dysmenorrhea (RR 0.42, 95% CI 0.34-0.53), but a higher risk of discontinuation due to bleeding issues (RR 2.83, 95% CI 2.47-3.25) and amenorrhea (RR 5.92, 95% CI 2.81-12.49). There were no significant differences between the two terms of continuation, expulsion, non-medical reasons for discontinuation, satisfaction, and other adverse outcomes.InterpretationLNG-IUDs and Cu-IUDs are both highly effective contraceptive methods. Compared to Cu-IUDs, LNG-IUDs were associated with a lower risk of pregnancy and adverse reactions. However, LNG-IUDs carry a higher risk of amenorrhea. When recommending contraceptive methods, healthcare providers should fully inform patients of these potential risks and consider patient preferences.FundingThe research was funded by Hunan Provincial Natural Foundation of China (2021JJ30040), the National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University (2021KFJJ06), and the National Natural Science Foundation of China (No. 81672225).
| S-EPMC11602564 | biostudies-literature
Project description:BackgroundIn the United States, more intrauterine device (IUD) users select levonorgestrel IUDs than copper IUDs for long-term contraception. Currently, clinicians offer only copper IUDs for emergency contraception because data are lacking on the efficacy of the levonorgestrel IUD for this purpose.MethodsThis randomized noninferiority trial, in which participants were unaware of the group assignments, was conducted at six clinics in Utah and included women who sought emergency contraception after at least one episode of unprotected intercourse within 5 days before presentation and agreed to placement of an IUD. We randomly assigned participants in a 1:1 ratio to receive a levonorgestrel 52-mg IUD or a copper T380A IUD. The primary outcome was a positive urine pregnancy test 1 month after IUD insertion. When a 1-month urine pregnancy test was unavailable, we used survey and health record data to determine pregnancy status. The prespecified noninferiority margin was 2.5 percentage points.ResultsAmong the 355 participants randomly assigned to receive levonorgestrel IUDs and 356 assigned to receive copper IUDs, 317 and 321, respectively, received the interventions and provided 1-month outcome data. Of these, 290 in the levonorgestrel group and 300 in the copper IUD group had a 1-month urine pregnancy test. In the modified intention-to-treat and per-protocol analyses, pregnancy rates were 1 in 317 (0.3%; 95% confidence interval [CI], 0.01 to 1.7) in the levonorgestrel group and 0 in 321 (0%; 95% CI, 0 to 1.1) in the copper IUD group; the between-group absolute difference in both analyses was 0.3 percentage points (95% CI, -0.9 to 1.8), consistent with the noninferiority of the levonorgestrel IUD to the copper IUD. Adverse events resulting in participants seeking medical care in the first month after IUD placement occurred in 5.2% of participants in the levonorgestrel IUD group and 4.9% of those in the copper IUD group.ConclusionsThe levonorgestrel IUD was noninferior to the copper IUD for emergency contraception. (Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT02175030.).
| S-EPMC7983017 | biostudies-literature
Project description:Globally, HIV/AIDS is a leading cause of morbidity worldwide among reproductive-aged cisgender women, highlighting the importance of understanding effects of contraceptives on HIV-1 risk. Some observational studies suggest there may be an increased risk of HIV-1 acquisition among women using the long-acting injectable progestin contraceptive, depo-medroxyprogesterone acetate. The potential mechanism of this susceptibility is unclear. There are few data on the role of the upper female reproductive tract in HIV-1 transmission, and the mechanisms of HIV-1 infection are likely to differ in the upper compared to the lower reproductive tract due to differences in tissue composition and variable effects of sex steroids on mucosal immune cell distribution and activity. In this study, we measured the susceptibility of mucosal immune cells from the upper female reproductive tract to HIV-1 entry using the virion-based HIV-1 fusion assay in samples from healthy female volunteers. We studied 37 infectious molecular clones for their ability to fuse to cells from endometrial biopsies in three participants and found that subtype (B or C) and origin of the virus (transmitted founder or chronic control) had little influence on HIV-1 fusion susceptibility. We studied the effect of contraceptives on HIV-1 susceptibility of immune cells from the cervix, endometrium and peripheral blood by comparing fusion susceptibility in four groups: users of the copper intrauterine device (IUD), levonorgestrel-containing oral contraceptive, levonorgestrel-containing IUD and unexposed controls (n = 58 participants). None of the contraceptives was associated with higher rates of HIV-1 entry into female reproductive tract cells compared to control samples from the mid-luteal phase.
| S-EPMC6705759 | biostudies-literature
Project description:ObjectivesReproductive aged women are at risk of pregnancy and sexually transmitted infections (STI). Understanding drivers of STI acquisition, including any association with widely used contraceptives, could help us to reduce STI prevalence and comorbidities. We compared the risk of STI among women randomised to three contraceptive methods.MethodsWe conducted a secondary analysis to assess the risk of chlamydia and gonorrhoea in a clinical trial evaluating HIV risk among 7829 women aged 16-35 randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) or a levonorgestrel (LNG) implant. We estimated chlamydia and gonorrhoea prevalences by contraceptive group and prevalence ratios (PR) using log-binomial regression.ResultsAt baseline, chlamydia and gonorrhoea prevalences were 18% and 5%, respectively. Final visit chlamydia prevalence did not differ significantly between DMPA-IM and copper IUD groups or between copper IUD and LNG implant groups. The DMPA-IM group had significantly lower risk of chlamydia compared with the LNG implant group (PR 0.83, 95% CI 0.72 to 0.95). Final visit gonorrhoea prevalence differed significantly only between the DMPA-IM and the copper IUD groups (PR 0.67, 95% CI 0.52 to 0.87).ConclusionsThe findings suggest that chlamydia and gonorrhoea risk may vary with contraceptive method use. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use.
| S-EPMC8165154 | biostudies-literature
Project description:ObjectivesExamine intrauterine device (IUD) switching or discontinuation up to 6 months after participant-masked randomization to different IUDs.Study designParticipants were randomized 1:1 to the copper T380A or levonorgestrel 52 mg IUD for emergency contraception and informed they could switch IUD type without cost at any time.ResultsOf the 327 subjects allocated to the levonorgestrel IUD, 7 (2.1%) switched their IUD type by 6 months versus 18 (5.5%) of the 328 copper IUD users (RR: 0.4 [95% CI: 0.2, 0.9], p = 0.03). Six-month IUD discontinuation occurred in 34 (10.4%) levonorgestrel and 35 (10.7%) copper IUD users.ConclusionIndividuals randomly assigned to IUD type at presentation for emergency contraception continue their assigned IUDs at high rates over 6 months.ImplicationsWhile many recruited individuals declined enrollment, those who accepted randomization had high continuation rates; the high continuation and low cross-over supports using IUD randomization as a tool for future investigation. Participants' similar rates of and reasons for switching and discontinuation by IUD type over the study period may impact clinical counseling.
| S-EPMC9839545 | biostudies-literature
Project description:ObjectiveTo determine the association between provider training level and postplacental intrauterine device (IUD) outcomes following insertion instruction by email only.Study designWe conducted a single-center chart review of demographics, insertion and clinical outcomes within 6 months of delivery for 116 patients who underwent postplacental levonorgestrel 52 mg IUD placement from October 1, 2016, to March 31, 2017.ResultsWe confirmed IUD retention, removal or expulsion in 87 of 116 (75.0%) patients by 6 months after delivery. Complete expulsion or removal for malposition occurred in 20 (23.0%) patients and more frequently after vaginal than cesarean delivery (30.2% vs. 4.2%, OR 9.93 [95% CI 1.25-78.96]) and when a postgraduate year (PGY) 1 physician placed the IUD compared to a PGY 2-4 or attending physician (37.5% vs. 14.5%, OR 3.52 [95% CI 1.25-9.94]).ConclusionPostplacental levonorgestrel 52 mg IUD expulsion rates are associated with provider training level as well as delivery route, though the individual association of each of these factors is difficult to ascertain given the high degree of collinearity between these two variables in our study.
| S-EPMC6351181 | biostudies-literature
Project description:BackgroundThe objective of this study was to assess the effect of timing of postpartum levonorgestrel-releasing intrauterine device (IUD) insertion on breast-feeding continuation.Study designWomen interested in using a levonorgestrel IUD postpartum were randomized to immediate postplacental insertion (postplacental group) or insertion 6-8 weeks after vaginal delivery (delayed group). Duration and exclusivity of breast-feeding were assessed at 6-8 weeks, 3 months, and 6 months postpartum. Only women who received an IUD were included in this analysis.ResultsBreast-feeding was initiated by 32 (64%) of 50 of women receiving a postplacental IUD and 27 (58.7%) of 46 of women receiving a delayed IUD (p=.59). More women in the delayed group compared with the postplacental group continued to breast-feed at 6-8 weeks (16/46 vs. 15/50, p=.62), 3 months (13/46 vs. 7/50, p=.13), and 6 months postpartum (11/46 vs. 3/50, p=.02). The results did not differ when only women who initiated breast-feeding or only primiparous women with no prior breast-feeding experience were analyzed.ConclusionsImmediate postplacental insertion of the levonorgestrel IUD is associated with shorter duration of breast-feeding and less exclusive breast-feeding. Further studies on the effects of early initiation of progestin-only methods on women's lactation experience are needed.
| S-EPMC3202348 | biostudies-literature
Project description:ObjectiveTo evaluate heavy menstrual bleeding treatment outcomes with levonorgestrel 52-mg intrauterine device (IUD) use in participants without body mass index (BMI) or parity restrictions.MethodsInvestigators included participants aged 18-50 years with no pelvic or systemic pathology causing heavy menstrual bleeding at 29 U.S. centers in a prospective trial. Participants had up to three screening cycles with menstrual product collection for alkaline hematin blood-loss measurements. Investigators enrolled those with two menses with blood loss of 80 mL or more (values averaged for baseline blood loss), placed the IUD, and followed participants for up to six 28-day cycles. Participants collected any menstrual products used during cycles 3 and 6 for blood-loss measurement. We evaluated outcomes in participants with at least one follow-up assessment for the primary outcome of median absolute blood-loss change and, secondarily, treatment success , defined as the proportion with a final measured blood loss less than 80 mL and at least 50% reduction from baseline. We evaluated exploratory outcomes of differences in blood-loss changes by BMI and parity using Wilcoxon rank sum test.ResultsOf 105 enrolled participants, 47 (44.8%) had obesity (BMI 30.0 or higher) and 29 (27.6%) were nulliparous. Baseline mean blood loss ranged from 73 to 520 mL (median 143 mL, interquartile range 112-196 mL). Eighty-nine (84.8%) had at least one evaluable follow-up evaluation. Participants had median (interquartile range) absolute blood-loss decreases at cycles 3 (n=86) and 6 (n=81) of 93.3% (86.1-97.7%) and 97.6% (90.4-100%), respectively. At cycle 6, participants without obesity (n=43) and with obesity (n=38) had similar median [interquartile range] decreases (97.6% [91.8-100%] and 97.5% [90.3-100%], respectively; P =.89), with comparable findings for nulliparous (n=25) and parous (n=56) participants (97.0% [91.7-99.1%] and 98.1% [89.9-100%], respectively; P =.43). Treatment success occurred in 81.8% (95% CI 74.2-89.4%) of 99 participants, excluding those with no outcomes due to lost to follow-up or consent withdrawal, and did not vary by BMI or parity. The most common adverse events leading to discontinuation were bleeding or cramping (n=6 [5.7%]) and expulsion (n=5 [4.8%]).ConclusionThis levonorgestrel 52-mg IUD reduces blood loss by more than 90% over 6 months compared with baseline for most users with heavy menstrual bleeding.Funding sourceMedicines360.Clinical trial registrationClinicalTrials.gov , NCT03642210.
| S-EPMC10108838 | biostudies-literature
Project description:The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls). Women (n = 251) from South Africa and Kenya were included. Twenty-seven cervicovaginal cytokines were measured by Luminex at baseline, and 1 and 6 months after contraceptive iTanko et alnitiation. In addition, cytokines were measured preseroconversion in HIV cases (n = 25) and controls (n = 100). At 6 months after contraceptive initiation, women using Cu-IUD had increased concentrations of 25/27 cytokines compared to their respective baseline concentrations. In contrast, women initiating DMPA-IM and LNG-implant did not experience changes in cervicovaginal cytokines. Preseroconversion concentrations of IL-1β, IL-6, and TNF-α, previously associated with HIV risk, correlated with increased HIV risk in a logistic regression analysis, although not significantly after correcting for multiple comparisons. Adjusting for contraceptive arm did not alter these results. Although Cu-IUD use broadly increased cervicovaginal cytokine concentrations at 6 months postinsertion, these inflammatory changes were found not to be a significant driver of HIV risk. NCT02550067.
| S-EPMC9470113 | biostudies-literature