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Open Access Journal of Contraception 2018Evidence on the association between contraceptive use and risk of sexually transmitted infections (STIs) and bacterial vaginosis (BV) is lacking, with few prospective... (Review)
Review
PURPOSE
Evidence on the association between contraceptive use and risk of sexually transmitted infections (STIs) and bacterial vaginosis (BV) is lacking, with few prospective studies. We systematically reviewed the last 10 years' evidence on the association between contraception and STI/BV, building on the most recent systematic reviews published in 2006 and 2009.
METHODS
We searched the MEDLINE and POPLINE databases for peer-reviewed articles p ublished between January 1, 2008 and January 31, 2018 reporting prospective studies that assessed the association between contraceptive use and incident STI and/or incident or recurrent BV.
RESULTS
We identified 33 articles that evaluated combined oral contraceptives (COC), depot medroxyprogesterone acetate (DMPA), the copper intrauterine device (Cu-IUD), the levonorgestrel intrauterine system (LNG-IUS) and other methods. The strength of the evidence for many specific contraceptive method/STI associations is limited by few prospective studies with comparably defined exposures and outcomes. Available data suggest no association of COCs and , , HSV-2 or syphilis, and mixed evidence on the association with HPV, , and BV. For DMPA, none of the studies identified found an association with or syphilis, and data on HPV and BV were mixed. Two large studies showed a highly clinically significant increased risk of HSV-2 infection with DMPA use. Data on the effect of Cu-IUD and the LNG-IUS on the acquisition of , and s are sparse, and data on HPV and BV are mixed.
CONCLUSION
Few data are available from prospective studies, including randomized trials, to draw strong conclusions about the relationships between contraceptive methods and specific STIs. The overall evidence on the association between contraceptive use and STI/BV risk is limited by the lack of any randomized trials, few published prospective studies designed to analyze these associations, wide variability in exposure definitions and comparator groups, potential for confounding due to inaccurate sexual behavior data, differential confounder adjustment and differences in study populations and sizes. Despite these limitations, new evidence is supportive of a significantly increased risk of HSV-2 infection among DMPA users which warrants additional research to better understand this association.
PubMed: 30519127
DOI: 10.2147/OAJC.S135439 -
The Linacre Quarterly Nov 2018Hormonal contraception (HC) is widely used throughout the world and has been associated with venous thrombosis (VT) such as deep vein thrombosis, pulmonary emboli, and... (Review)
Review
BACKGROUND
Hormonal contraception (HC) is widely used throughout the world and has been associated with venous thrombosis (VT) such as deep vein thrombosis, pulmonary emboli, and cerebral VT.
OBJECTIVES
To provide a current comprehensive overview of the risk of objectively confirmed VT with HC in healthy women compared to nonusers.
SEARCH METHODS
PubMed was searched from inception to April 2018 for eligible studies in the English language, with hand searching from past systematic reviews.
SELECTION CRITERIA
We selected original research evaluating risk of objectively confirmed VT in healthy women taking oral or nonoral HC compared with nonusers.
DATA COLLECTION
The primary outcome of interest was a fatal or nonfatal VT in users of HC compared to nonusers or past users. Studies with at least twenty events were eligible. Adjusted relative risks with 95 percent confidence intervals were reported. Three independent reviewers extracted data from selected studies.
RESULTS
1,962 publications were retrieved through the search strategy, with 15 publications included. Users of oral contraception with levonorgesterol had increased risk of VT by a range of 2.79-4.07, while other oral hormonal preparations increased risk by 4.0-48.6. Levonorgestrel intrauterine devices did not increase risk. Etonogestrel/ethinyl estradiol vaginal rings increased the risk of VT by 6.5. Norelgestromin/ethinyl estradiol patches increased risk of VT by 7.9. Etonogestrel subcutaneous implants by 1.4 and depot-medroxyprogesterone by 3.6. The risk of fatal VT was increased in women aged fifteen to twenty-four by 18.8-fold.
CONCLUSION
Users of HC have a significant increased risk of VT compared to nonusers. Current risks would project at least 300-400 healthy young women dying yearly in the United States due to HC. Women should be informed of these risks and offered education in fertility-awareness-based methods with comparable efficacy for family planning.
SUMMARY
HC is widely used throughout the world and has been associated with blood clots in the legs and lungs. We searched the literature and found the risks of currently used forms of birth control increased between three- and ninefold for blood clots for healthy women. The risks found would project 300-400 women dying from using HC each year in the United States.
PubMed: 32431379
DOI: 10.1177/0024363918816683 -
American Journal of Preventive Medicine Nov 2018The objective of this systematic review was to update a prior review and summarize the evidence on the impact of family planning reminder systems (e.g., daily text...
CONTEXT
The objective of this systematic review was to update a prior review and summarize the evidence on the impact of family planning reminder systems (e.g., daily text messages reminding oral contraception users to take a pill).
EVIDENCE ACQUISITION
Multiple databases, including PubMed, were searched during 2016-2017 for articles published from March 1, 2011, to November 30, 2016, describing studies of reminder systems.
EVIDENCE SYNTHESIS
The search strategy identified 24,953 articles, of which two studies met the inclusion criteria. In total with the initial review, four studies (including two RCTs) examined reminder systems among oral contraception users, with two of three that examined correct use finding a statistically significant positive impact, and one RCT finding a positive impact on knowledge and continuation. Of three studies (including two RCTs) that examined reminder systems among depot medroxyprogesterone acetate users, one of three that examined correct use found a statistically significant positive impact on timely injections at 3 months, and one study found no effect on continued use at 12 months.
CONCLUSIONS
Although this review found mixed support for the effectiveness of reminder systems on family planning behaviors, the highest quality evidence yielded null findings related to correct use of oral contraception and timely depot medroxyprogesterone acetate injections beyond 3 months, and found positive findings related to oral contraception continuation and knowledge. Future studies would be strengthened by objectively measuring outcomes and examining additional contraceptive methods and outcomes at least 12 months post-intervention.
THEME INFORMATION
This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services.
Topics: Contraception; Contraception Behavior; Family Planning Services; Humans; Randomized Controlled Trials as Topic; Reminder Systems; Text Messaging; United States; United States Dept. of Health and Human Services
PubMed: 30342634
DOI: 10.1016/j.amepre.2018.07.009 -
Brazilian Journal of Medical and... 2018Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic... (Review)
Review
Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic review of studies describing dietary intake or eating behavior in DMPA users to understand whether the use of DMPA is associated with changes in dietary habits and behaviors leading to weight gain. We searched the PubMed, POPLINE, CENTRAL Cochrane, Web of Science, and EMBASE databases for reports published in English between 1980 and 2017 examining dietary intake or eating behavior in healthy women in reproductive age and adolescents using DMPA (150 mg/mL). Of the 749 publications screened, we excluded 742 due to duplicates (96), not addressing the key research question (638), not reporting dietary intake data (4), and not evaluating the relationship of body weight and dietary or eating behaviors (4). We identified seven relevant studies, including one randomized placebo-controlled trial, one non-randomized paired clinical trial, and five cohort studies. The randomized trial found no association and the other reports were inconsistent. Findings varied from no change in dietary intake or eating behavior with DMPA use to increased appetite in the first six months of DMPA use. Few studies report dietary intake and eating behavior in DMPA users and the available data are insufficient to conclude whether DMPA use is associated with changes in dietary habits or behavior leading to weight gain.
Topics: Body Mass Index; Clinical Trials as Topic; Contraceptive Agents, Female; Energy Intake; Feeding Behavior; Female; Humans; Medroxyprogesterone Acetate; Weight Gain
PubMed: 29694506
DOI: 10.1590/1414-431x20187575 -
Endocrine Dec 2017Sex hormones play a role in bone density, cardiovascular health, and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Sex hormones play a role in bone density, cardiovascular health, and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to manage symptoms and to protect against adverse long-term health outcomes. Yet, the effectiveness of HT in preventing adverse outcomes has not been systematically assessed. We summarize the evidence regarding effects of HT on bone and cardiovascular health in women with POI.
METHODS
A comprehensive search of the electronic databases MEDLINE, EMBASE, and Scopus was conducted by a medical reference librarian from database inception to January 2016. Randomized trials and observational cohort studies with an estrogen-based HT intervention in women with POI under the age of 40 were included. Reviewers worked independently and in duplicate to assess eligibility and risk of bias, and extract data of interest from each study.
RESULTS
The search identified 1670 articles; 12 met inclusion criteria. Four randomized clinical trials and eight cohort studies at high risk of bias enrolled 806 women with POI. The most common HT formulations were transdermal estradiol and oral conjugated equine estrogen combined with medroxyprogesterone acetate. Bone mineral density was the most frequent outcome, with three out of eight studies showing HT associated increase benefits. Only one study reported effects on fractures or vasomotor symptoms and none on cardiovascular mortality. Results regarding lipid profiles were inconsistent.
CONCLUSIONS
Evidence supporting bone and cardiovascular benefits of HT in women with POI is limited by high risk of bias, reliance on surrogate outcomes, and heterogeneity of trials regarding the formulation, dose, route of administration, and regimen of HT. Further research addressing patient important outcomes such as fractures, stroke, and cardiovascular mortality are crucial to optimize benefits of this therapy.
Topics: Adult; Estrogen Replacement Therapy; Estrogens; Female; Humans; Middle Aged; Primary Ovarian Insufficiency
PubMed: 29039146
DOI: 10.1007/s12020-017-1435-x -
Journal of Musculoskeletal & Neuronal... Sep 2017To assess whether progesterone (P4) or osteoblast P4 receptor-acting progestin (P) contributed to estrogen (E) therapy-related increased areal bone mineral density (BMD)... (Meta-Analysis)
Meta-Analysis Review
Estrogen-progestin therapy causes a greater increase in spinal bone mineral density than estrogen therapy - a systematic review and meta-analysis of controlled trials with direct randomization.
OBJECTIVE
To assess whether progesterone (P4) or osteoblast P4 receptor-acting progestin (P) contributed to estrogen (E) therapy-related increased areal bone mineral density (BMD) in randomized controlled trials (RCT) with direct randomization to estrogen (ET) or estrogen-progestin (EPT) therapy.
METHODS
Systematic literature searches in biomedical databases identified RCT with direct randomization and parallel estrogen doses that measured spinal BMD change/year. Cyclic P4/P was included in this random effects meta-analysis only if for ≥ half the number of E-days.
RESULTS
Searches yielded 155 publications; five met inclusion criteria providing eight dose-parallel ET-EPT comparisons in 1058 women. Women averaged mid-50 years, ⟨five years into menopause and took conjugated equine E daily at 0.625 mg with/without 2.5 mg medroxyprogesterone acetate (MPA). The weighted mean EPT minus ET percentage difference in spinal BMD change was +0.68%/year (95% CI 0.38, 0.97%) (P=0.00001). This result was highly heterogeneous (I²=81%) but this may reflect the small number of studies.
CONCLUSION
Estrogen with an osteoblast P4R-acting progestin (EPT) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET. These data have implications for management of vasomotor symptoms and potentially for osteoporosis treatment in menopausal women.
Topics: Bone Density; Estrogens; Female; Humans; Osteoporosis, Postmenopausal; Progestins; Randomized Controlled Trials as Topic
PubMed: 28860416
DOI: No ID Found -
AIDS (London, England) Apr 2017To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. (Review)
Review
OBJECTIVE
To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals.
DESIGN
Systematic review of the published literature.
METHODS
We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses.
RESULTS
Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives.
CONCLUSION
Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices.
Topics: Anti-Retroviral Agents; Contraceptives, Oral, Hormonal; Drug Interactions; Female; Humans
PubMed: 28060009
DOI: 10.1097/QAD.0000000000001392 -
Fertility and Sterility Feb 2017To investigate whether treatment with progestogens in the first trimester of pregnancy would decrease the incidence of miscarriage in women with a history of unexplained... (Meta-Analysis)
Meta-Analysis Review
Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials.
OBJECTIVE
To investigate whether treatment with progestogens in the first trimester of pregnancy would decrease the incidence of miscarriage in women with a history of unexplained recurrent miscarriage.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Women with a history of unexplained recurrent miscarriage.
INTERVENTION(S)
Randomized, controlled trials were identified by searching electronic databases. We included randomized, controlled trials comparing supplementation with progestogens (i.e., intervention group) in the first trimester of pregnancy with control (either placebo or no treatment) in women with a history of recurrent miscarriage. All types of progestogens, including natural P and synthetic progestins, were analyzed.
MAIN OUTCOME MEASURE(S)
The primary outcome was the incidence of miscarriage. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI).
RESULT(S)
Ten trials including 1,586 women with recurrent miscarriage were analyzed. Eight studies used placebo as control and were double-blind. Regarding the intervention, two RCTs used natural P, whereas the other eight studies used progestins: medroxyprogesterone, cyclopentylenol ether of progesterone, dydrogesterone, or 17-hydroxyprogesterone caproate. Pooled data from the 10 trials showed that women with a history of unexplained recurrent miscarriage who were randomized to the progestogens group in the first trimester and before 16 weeks had a lower risk of recurrent miscarriage (RR 0.72, 95% CI 0.53-0.97) and higher live birth rate (RR 1.07, 95% CI 1.02-1.15) compared with those who did not. No statistically significant differences were found in the other secondary outcomes, including preterm birth (RR 1.09, 95% CI 0.71-1.66), neonatal mortality (RR 1.80, 95% CI 0.44-7.34), and fetal genital abnormalities (RR 1.68, 95% CI 0.22-12.62).
CONCLUSION(S)
Our findings provide evidence that supplementation with progestogens may reduce the incidence of recurrent miscarriages and seem to be safe for the fetuses. Synthetic progestogens, including weekly IM 17-hydroxyprogesterone caproate, but not natural P, were associated with a lower risk of recurrent miscarriage. Given the limitations of the studies included in our meta-analysis, it is difficult to recommend route and dose of progestogen therapy. Further head-to-head trials of P types, dosing, and route of administration are required.
Topics: Abortion, Habitual; Chi-Square Distribution; Drug Administration Schedule; Female; Humans; Odds Ratio; Pregnancy; Pregnancy Trimester, First; Progestins; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27887710
DOI: 10.1016/j.fertnstert.2016.10.031 -
AIDS (London, England) Nov 2016Some studies suggest that specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase women's HIV acquisition risk. We... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE AND DESIGN
Some studies suggest that specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data.
METHODS
We searched for articles published between 15 January 2014 and 15 January 2016 and hand-searched reference lists. We identified longitudinal studies comparing users of a specific hormonal contraceptive method against either nonusers of hormonal contraception or users of another specific hormonal contraceptive method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus non-use of hormonal contraception.
RESULTS
We identified 10 new reports of which five were considered 'unlikely to inform the primary question'. We focus on the other five reports, along with nine from the previous review, which were considered 'informative but with important limitations'. The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate, and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher quality studies on DMPA (or nondisaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher quality studies of hazard ratio 1.4.
CONCLUSION
Although confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely hazard ratio 1.5 or less. Data for other hormonal contraceptive methods, including norethisterone enanthate, are largely reassuring.
Topics: Contraception; Contraceptive Agents, Female; Female; HIV Infections; Humans; Risk Assessment
PubMed: 27500670
DOI: 10.1097/QAD.0000000000001228 -
The Cochrane Database of Systematic... Aug 2016Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. POCs include injectables, intrauterine contraception,... (Review)
Review
BACKGROUND
Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. POCs include injectables, intrauterine contraception, implants, and oral contraceptives. Many POCs are long-acting, cost-effective methods of preventing pregnancy. However, concern about weight gain can deter the initiation of contraceptives and cause early discontinuation among users.
OBJECTIVES
The primary objective was to evaluate the association between progestin-only contraceptive use and changes in body weight.
SEARCH METHODS
Until 4 August 2016, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP. For the initial review, we contacted investigators to identify other trials.
SELECTION CRITERIA
We considered comparative studies that examined a POC versus another contraceptive method or no contraceptive. The primary outcome was mean change in body weight or mean change in body composition. We also considered the dichotomous outcome of loss or gain of a specified amount of weight.
DATA COLLECTION AND ANALYSIS
Two authors extracted the data. Non-randomized studies (NRS) need to control for confounding factors. We used adjusted measures for the primary effects in NRS or the results of matched analysis from paired samples. If the report did not provide adjusted measures for the primary analysis, we used unadjusted outcomes. For RCTs and NRS without adjusted measures, we computed the mean difference (MD) with 95% confidence interval (CI) for continuous variables. For dichotomous outcomes, we calculated the Mantel-Haenszel odds ratio (OR) with 95% CI.
MAIN RESULTS
We found 22 eligible studies that included a total of 11,450 women. With 6 NRS added to this update, the review includes 17 NRS and 5 RCTs. By contraceptive method, the review has 16 studies of depot medroxyprogesterone acetate (DMPA), 4 of levonorgestrel-releasing intrauterine contraception (LNG-IUC), 5 for implants, and 2 for progestin-only pills.Comparison groups did not differ significantly for weight change or other body composition measure in 15 studies. Five studies with moderate or low quality evidence showed differences between study arms. Two studies of a six-rod implant also indicated some differences, but the evidence was low quality.Three studies showed differences for DMPA users compared with women not using a hormonal method. In a retrospective study, weight gain (kg) was greater for DMPA versus copper (Cu) IUC in years one (MD 2.28, 95% CI 1.79 to 2.77), two (MD 2.71, 95% CI 2.12 to 3.30), and three (MD 3.17, 95% CI 2.51 to 3.83). A prospective study showed adolescents using DMPA had a greater increase in body fat (%) compared with a group not using a hormonal method (MD 11.00, 95% CI 2.64 to 19.36). The DMPA group also had a greater decrease in lean body mass (%) (MD -4.00, 95% CI -6.93 to -1.07). A more recent retrospective study reported greater mean increases with use of DMPA versus Cu IUC for weight (kg) at years 1 (1.3 vs 0.2), 4 (3.5 vs 1.9), and 10 (6.6 vs 4.9).Two studies reported a greater mean increase in body fat mass (%) for POC users versus women not using a hormonal method. The method was LNG-IUC in two studies (reported means 2.5 versus -1.3; P = 0.029); (MD 1.60, 95% CI 0.45 to 2.75). One also studied a desogestrel-containing pill (MD 3.30, 95% CI 2.08 to 4.52). Both studies showed a greater decrease in lean body mass among POC users.
AUTHORS' CONCLUSIONS
We considered the overall quality of evidence to be low; more than half of the studies had low quality evidence. The main reasons for downgrading were lack of randomizations (NRS) and high loss to follow-up or early discontinuation.These 22 studies showed limited evidence of change in weight or body composition with use of POCs. Mean weight gain at 6 or 12 months was less than 2 kg (4.4 lb) for most studies. Those with multiyear data showed mean weight change was approximately twice as much at two to four years than at one year, but generally the study groups did not differ significantly. Appropriate counseling about typical weight gain may help reduce discontinuation of contraceptives due to perceptions of weight gain.
Topics: Adolescent; Adult; Body Composition; Body Weight; Contraceptives, Oral, Hormonal; Drug Implants; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone Acetate; Progestins; Prospective Studies; Retrospective Studies; Weight Gain
PubMed: 27567593
DOI: 10.1002/14651858.CD008815.pub4