Effects of the Levonorgestrel-containing Intrauterine Device, Copper Intrauterine Device, and Levonorgestrel-Containing Oral Contraceptive on the Endometrial and Cervical Transcriptomes Offer Insights into Mechanisms of Action of Intrauterine Devices
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PROVIDER: PRJNA568201 | ENA |
REPOSITORIES: ENA
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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:BACKGROUND:US unintended pregnancy rates remain high, and contraceptive providers are not universally trained to offer intrauterine devices and implants to women who wish to use these methods. OBJECTIVE:We sought to measure the impact of a provider training intervention on integration of intrauterine devices and implants into contraceptive care. STUDY DESIGN:We measured the impact of a continuing medical education-accredited provider training intervention on provider attitudes, knowledge, and practices in a cluster randomized trial in 40 US health centers from 2011 through 2013. Twenty clinics were randomly assigned to the intervention arm; 20 offered routine care. Clinic staff participated in baseline and 1-year surveys assessing intrauterine device and implant knowledge, attitudes, and practices. We used a difference-in-differences approach to compare changes that occurred in the intervention sites to changes in the control sites 1 year later. Prespecified outcome measures included: knowledge of patient eligibility for intrauterine devices and implants; attitudes about method safety; and counseling practices. We used multivariable regression with generalized estimating equations to account for clustering by clinic to examine intervention effects on provider outcomes 1 year later. RESULTS:Overall, we surveyed 576 clinic staff (314 intervention, 262 control) at baseline and/or 1-year follow-up. The change in proportion of providers who believed that the intrauterine device was safe was greater in intervention (60% at baseline to 76% at follow-up) than control sites (66% at both times) (adjusted odds ratio, 2.48; 95% confidence interval, 1.13-5.4). Likewise, for the implant, the proportion increased from 57-77% in intervention, compared to 61-65% in control sites (adjusted odds ratio, 2.57; 95% confidence interval, 1.44-4.59). The proportion of providers who believed they were experienced to counsel on intrauterine devices also increased in intervention (53-67%) and remained the same in control sites (60%) (adjusted odds ratio, 1.89; 95% confidence interval, 1.04-3.44), and for the implant increased more in intervention (41-62%) compared to control sites (48-50%) (adjusted odds ratio, 2.30; 95% confidence interval, 1.28-4.12). Knowledge scores of patient eligibility for intrauterine devices increased at intervention sites (from 0.77-0.86) 6% more over time compared to control sites (from 0.78-0.80) (adjusted coefficient, 0.058; 95% confidence interval, 0.003-0.113). Knowledge scores of eligibility for intrauterine device and implant use with common medical conditions increased 15% more in intervention (0.65-0.79) compared to control sites (0.67-0.66) (adjusted coefficient, 0.15; 95% confidence interval, 0.09-0.21). Routine discussion of intrauterine devices and implants by providers in intervention sites increased significantly, 71-87%, compared to in control sites, 76-82% (adjusted odds ratio, 1.97; 95% confidence interval, 1.02-3.80). CONCLUSION:Professional guidelines encourage intrauterine device and implant competency for all contraceptive care providers. Integrating these methods into routine care is important for access. This replicable training intervention translating evidence into care had a sustained impact on provider attitudes, knowledge, and counseling practices, demonstrating significant changes in clinical care a full year after the training intervention.
| S-EPMC5970088 | biostudies-literature
Project description:RATIONALE: The use of intrauterine levonorgestrel may prevent atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome. It is not yet known whether intrauterine levonorgestrel and observation are more effective than observation alone in preventing atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome.
PURPOSE: This randomized phase III trial is studying intrauterine levonorgestrel and observation to see how well they work compared with observation alone in preventing atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome.
| 2047003 | ecrin-mdr-crc
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:PurposeTo investigate the association between intrauterine device (IUD) use and hip pain, orthopaedic visits for hip pain, and arthroscopic hip surgery.MethodsThis was a retrospective cohort study of patients aged 18-44 years old using either IUDs or subdermal implants for contraception in a large commercial claims database (MarketScan) from 2012 to 2015. All patients had at least 12 months of continuous enrollment both before and after contraceptive placement. Patients with a history of hip pain or surgery were excluded. The primary outcome was new hip pain. Secondary outcomes included visiting an orthopaedic or sports medicine provider for a hip complaint, intra-articular hip injection, and arthroscopic hip surgery. Outcomes were analyzed with Cox proportional-hazard models.ResultsWe identified a total of 242,383 patients, including 216,541 (89.3%) with IUDs and 25,842 (10.7%) with subdermal contraceptive implants. In time-to-event analysis, IUDs (vs implants) were not associated with increased risk of new hip pain diagnoses (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.87-1.03, P = .21). In contrast, both age (P < .001) and region (P < .001) were associated with increased risk of new hip pain. Similar results were seen for the secondary outcomes, including risk of orthopaedic visits for hip complaints (HR 1.06, 95% CI 0.83-1.35, P = .63), intra-articular injections of the hip (HR 0.94, 95% CI 0.63-1.41, P = .77), and hip arthroscopy procedures (HR 1.13, 95% CI 0.53-2.40, P = .75).ConclusionsIn this study, we found no evidence that IUDs were associated with hip pain or surgery.Level of evidenceLevel III, retrospective cohort.
| S-EPMC8527253 | biostudies-literature
Project description:Background30 years after the introduction of the levonorgestrel-releasing intrauterine device in Europe, several sub-Saharan African countries are seeking to broaden access to this contraceptive method. In this study, we aimed to assess 12-month continuation of the hormonal intrauterine device, copper intrauterine device, and implants, as well as to assess women's experiences and satisfaction using these methods in the private sector in Nigeria and the public sector in Zambia.MethodsWe did a prospective cohort study of long-acting reversible contraceptive users across 40 private sector clinics in Nigeria and 21 public sector clinics in Zambia. Eligible women were aged 18-49 years in Nigeria and 16-49 years in Zambia, had chosen to receive the hormonal intrauterine device, copper intrauterine device, or implant (either a 5-year levonorgestrel-releasing subdermal implant or a 3-year etonogestrel-releasing subdermal implant), and, in Nigeria only, had access to a telephone. Women were interviewed within 100 days of receiving their contraceptive method either via telephone in Nigeria or in person in Zambia, with follow-up surveys at 6 months and 12 months. The primary outcomes were method-specific, 12-month continuation rates-ie, continuation rates of the hormonal intrauterine device, copper intrauterine device, and implant across Nigeria and Zambia. We used Kaplan-Meier methods to estimate the cumulative probabilities of method-specific continuation and a log-rank test to compare contraceptive methods. We analysed self-reported satisfaction and experiences as a secondary outcome.FindingsBetween June 25 and Nov 22, 2018, we enrolled a total of 1542 women (n=860 in Nigeria and n=682 in Zambia) receiving a long-acting reversible contraceptive. In total, 835 women (266 [32%] hormonal intrauterine device users, 274 [33%] copper intrauterine device users, and 295 [35%] implant users) in Nigeria and 367 (140 [38%] hormonal intrauterine device users, 149 [40%] copper intrauterine device users, and 78 [21%] implant users) in Zambia were included in the study analysis. The 12-month cumulative continuation rates were 86·8% (95% CI 82·1-90·4) for the hormonal intrauterine device, 86·9% (82·1-90·4) for the copper intrauterine device, and 85·0% (80·2-88·7) for implants in Nigeria. In Zambia, the 12-month cumulative continuation rates were 94·7% (89·2-97·4) for the hormonal intrauterine device, 89·1% (82·3-93·4) for the copper intrauterine device, and 83·1% (72·2-90·1) for implants. At least 71% of respondents across the timepoints were very satisfied with their method, and at least 55 (79%) of 70 reported having recommended their contraceptive method to someone else. Across the methods, the most commonly self-reported positive aspect of long-acting reversible contraceptive use at 12 months was effectiveness in Nigeria (range 93-94%) and long-lasting duration in Zambia (48-60%). Between 124 (50%) of 248 and 136 (59%) of 230 Nigerian participants and 26 (42%) of 62 and 66 (57%) of 117 Zambian participants reported nothing negative about their contraceptive method.InterpretationOur study showed high continuation rates and satisfaction across long-acting reversible contraceptives, including the hormonal intrauterine device, a method that has been largely underused in sub-Saharan Africa. This finding supports the inclusion of the hormonal intrauterine device as a valuable addition to the mix of contraceptive methods in Nigeria and Zambia.FundingBill & Melinda Gates Foundation.
| S-EPMC8440225 | biostudies-literature
Project description:Patients with endometrial hyperplasia representing preliminary stages of endometrial cancer have shown to respond to therapy in 100% of the cases when treated with levonorgestrel -impregnated intrauterine device. Antiproliferative effect has also been reported after application of an anti-progestin impregnated intrauterine device which showed to induce endometrial atrophy. The intention of the present study was to obtain more information of novel therapeutic targets for hormonal treatment in endometrial hyperplasia and endometrial cancers. Gene expression of signaling pathways after stimulation of Ishikawa cells with high doses of progesterone (10 μM) or Mifepristone (10 μM) was performed. After using an oligo microarrays representing 24,650 human genes and 37,580 gene transcripts, 6,154 genes remained after pre-processing and filtering. This resulted in a total of 993 up-regulated genes with 189 genes for progesterone and 255 genes for Mifepristone. The 550 down regulated genes were distributed with 256 genes for progesterone, 127 genes for RU 486. The results showed that genes presenting the epidermal growth factor (EGF)/MAP-kinase pathway were significantly over-represented by progesterone treatment, whereas, by Mifepristone treatment genes involved in the p53 pathway were also up-regulated (data not shown). These genes may be interesting as potential new therapeutic targets in endometrial hyperplasia and endometrial cancer, as candidate genes for therapy response or as candidate markers for tumor progression. 20 samples, 4 different condition groups with 5 replicates for each group, linear factorial experimental design. Short time (4hrs) dose response to progesterone and Mifepristone in combination and alone. Only 18 samples are represented in this Series.
2010-05-06 | E-GEOD-14713 | biostudies-arrayexpress
Project description:Some evidence suggests that contraceptive use may influence the female genital tract (FGT) mucosal environment. However, comparative analysis of the effects of the most commonly used hormonal and non-hormonal contraceptives on the FGT host gene expression profile have not been evaluated in detail in a randomized clinical trial setting. Among 188 women enrolled in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial (Clinicaltrials.gov ID NCT02550067) between December 2015 and September 2017, we evaluated the effect of three contraceptive methods, injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant, and a non-hormonal T-380 copper intrauterine contraceptive device (Cu-IUD), on the endocervical host transcriptome at baseline and after one month of randomized contraceptive use, using RNA-Seq transcriptomic analysis.
2023-09-13 | GSE190923 | GEO
Project description:Intrauterine contraceptive devices (IUCD) are a safe and cost-effective contraceptive method for medically eligible women. Despite this, the utilisation rate for IUCDs is relatively low in many high-income countries, including Australia. Provision of education and training regarding IUCDs to healthcare providers, including nurses and midwives, is one approach to overcome some of the barriers that may prevent wider uptake of IUCDs. This study aims to explore the types and impact of IUCD insertion training for healthcare providers. A systematic review was undertaken in January 2017 to determine the effectiveness of IUCD training for healthcare providers in relation to provision of IUCDs to women. The databases MEDLINE, EMBASE, CINAHL, COCHRANE and SCOPUS were searched to identify studies from high-income countries relating to IUCD training for healthcare providers and relevant outcomes. A total of 30 studies were included in the review. IUCD training for healthcare providers contributed to increased knowledge and improved positive attitudes towards IUCDs, high rates of successful insertions, low complication rates, and increased provision of IUCDs. Successful insertions and low complication rates were similar across different healthcare provider types. No notable differences between provider types in terms of knowledge increase or insertion outcomes were observed. Different training programs for healthcare providers were found to be effective in improving knowledge and successful provision of IUCDs. Increasing the number of healthcare providers skilled in IUCD insertions in high-income countries, including nurses and midwives, will enhance access to this method of contraception and allow women greater contraceptive choice.
| S-EPMC6629157 | biostudies-literature
Project description:Epidemiological studies indicate that progestin-containing contraceptives may increase susceptibility to HIV and other infections; however, underlying mechanisms involving the upper female reproductive tract are undefined. To determine the effects of depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) on gene expression and physiology of the human endometrial and cervical transformation zone (TZ), microarray analyses were performed on whole tissue biopsies. In endometrium, activated pathways included leukocyte chemotaxis, attachment, and inflammation in DMPA (z>2.5) and LNG-IUS (z>3.5) users, and regulation of pattern recognition receptors and other immune mediators. In cervical TZ, progestin treatment altered expression of tissue remodeling and viability genes, but not those of immune functions. Together, these results indicate that progestins influence expression of immune-related genes in endometrium that would be expected to result in the local recruitment of HIV target cells, and thus may increase HIV susceptibility. It is important to consider the upper reproductive tract in the assessment of effects of contraceptives that may influence susceptibility to pathogens, such as HIV.
2014-11-21 | GSE60129 | GEO