Hormonal contraceptive use and depressive symptoms: systematic review and network meta-analysis of randomised trials.
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ABSTRACT: Background
Observational studies suggest that hormonal contraceptive use may increase depressive symptoms in women, but it is unclear whether the effect is causal.Aims
To quantitatively examine the evidence from randomised clinical trials for the link between hormonal contraceptive use and depressive symptoms.Method
We performed a systematic review and network meta-analysis of randomised clinical trials comparing women randomised to any form of a hormonal contraceptive with women randomised to any other form of a (non-)hormonal contraceptive or placebo. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsycINFO, EMCare and EMBASE, from inception to 1 May 2020. Certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. A random-effect Bayesian network meta-analysis was conducted, with change in depressive symptoms between baseline and three cycles as outcome.Results
This review identified 3492 records, of which 14 trials were eligible and 12 could be included in the network meta-analysis. These trials included 5833 participants (mean age per study range: 16.8-32.4 years) and compared 10 different interventions. Compared with placebo, hormonal contraceptive use did not cause worsening of depressive symptoms (standardised mean difference: median, -0.04; range, -0.17 [95% credible interval -0.46 to 0.13] to 0.13 [95% credible interval -0.28 to 0.56]).Conclusions
This study suggests that hormonal contraceptive use does not lead to an increase in depressive symptoms in adult women. Future studies should include first-time users, to confirm the results in young women.
SUBMITTER: de Wit AE
PROVIDER: S-EPMC8220855 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There are 150 million women worldwide using combined or progestogen-only hormonal contraceptive methods who may be at risk of sexually transmitted infections (STIs). Previous systematic reviews that have sought to establish whether there is an aetiological association between hormonal contraceptive methods/use and STIs have been limited in their methods and have mixed findings. We sought to update these reviews using appropriate control groups. We undertook a systematic review following the PRISMA guidelines and meta-analysis to examine the association between the use of all hormonal contraceptive methods and the acquisition of STIs (Neisseria gonorrhoeae, syphilis/Treponema pallidum, Chlamydia trachomatis, herpes simplex virus, and Trichomonas vaginalis) and/or bacterial vaginosis in literature published between 2005 and 2020. We analysed the effect of hormonal contraceptive methods/use separately on the prevalence, incidence and recurrence of STIs. A total of 37 studies were included in this review that reported 61 associations, in which 27 prevalence, eight incidence and two recurrence studies provided 43, 16, and two associations, respectively. We observed a positive association between hormonal contraceptive methods/use and the risk of chlamydia and herpes but a negative association for trichomoniasis and vaginosis. A negative but statistically insignificant association was observed between hormonal contraceptive methods/use and gonorrhoea. Hormonal contraceptive methods/use influences a woman's risk of STIs/ bacterial vaginosis, but the risk may differ depending on the type of STI. These findings should be contextualized carefully, particularly when formulating practice guidelines and policy, as the effects of hormonal contraceptive methods/use on the risk of STIs varied in direction when analysed separately by STI.
| S-EPMC9700818 | biostudies-literature
Project description:BACKGROUND:Depression is common in patients with coronary artery disease (CAD) and is associated with poorer outcomes and higher costs. Several randomised controlled trials (RCTs) targeting depression, of various modalities (including pharmacological, psychotherapeutic and other approaches), have been conducted and summarised in pairwise meta-analytic reviews. However, no study has considered the cumulative evidence within a network, which can provide valuable indirect comparisons and information about the relative efficacy of interventions. Therefore, we will adopt a review of review methodology to develop a network meta-analysis (NMA) of depression interventions for depression in CAD. METHODS:We will search relevant databases from inception for systematic reviews of RCTs of depression treatments for people with CAD, supplementing this with comprehensive searches for recent or ongoing studies. We will extract data from and summarise characteristics of individual RCTs, including participants, study characteristics, outcome measures and adverse events. Cochrane risk of bias ratings will also be extracted or if not present will be conducted by the authors. RCTs that compare depression treatments (grouped as pharmacological, psychotherapeutic, combined pharmacological/psychotherapeutic, exercise, collaborative care) to placebo, usual care, waitlist control or attention controls, or directly in head-to-head comparisons, will be included. Primary outcomes will be the change in depressive symptoms (summarised with a standardised mean difference) and treatment acceptability (treatment discontinuation: % of people who withdrew). Secondary outcomes will include change in 6-month depression outcomes, health-related quality of life (HRQoL), mortality, cardiovascular morbidity, health services use and adverse events. Secondary analyses will form further networks with individual anti-depressants and psychotherapies. We will use frequentist, random effects multivariate network meta-analysis to synthesise the evidence for depression intervention and to achieve a ranking of treatments, using Stata. Rankograms and surface under the cumulative ranking curves will be used for treatment ranking. Local and global methods will evaluate consistency. GRADE will be used to assess evidence quality for primary outcomes. DISCUSSION:The present review will address uncertainties about the evidence in terms of depression management in CAD and may allow for a ranking of treatments, including providing important information for future research efforts. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42018108293.
| S-EPMC6420728 | biostudies-literature
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Project description:Vaginal microbiome in response to hormonal contraceptive use
| PRJEB30774 | ENA
Project description:ImportanceMeta-analyses have reported conflicting data on the safety of hormonal contraception, but the quality of evidence for the associations between hormonal contraceptive use and adverse health outcomes has not been quantified in aggregate.ObjectiveTo grade the evidence from meta-analyses of randomized clinical trials (RCTs) and cohort studies that assessed the associations between hormonal contraceptive use and adverse health outcomes among women.Data sourcesMEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched from database inception to August 2020. Search terms included hormonal contraception, contraceptive agents, progesterone, desogestrel, norethindrone, megestrol, algestone, norprogesterones, and levonorgestrel combined with terms such as systematic review or meta-analysis.Evidence reviewThe methodological quality of each meta-analysis was graded using the Assessment of Multiple Systematic Reviews, version 2, which rated quality as critically low, low, moderate, or high. The Grading of Recommendation, Assessment, Development and Evaluations approach was used to assess the certainty of evidence in meta-analyses of RCTs, with evidence graded as very low, low, moderate, or high. Evidence of associations from meta-analyses of cohort studies was ranked according to established criteria as nonsignificant, weak, suggestive, highly suggestive, or convincing.ResultsA total of 2996 records were screened; of those, 310 full-text articles were assessed for eligibility, and 58 articles (13 meta-analyses of RCTs and 45 meta-analyses of cohort studies) were selected for evidence synthesis. Sixty associations were described in meta-analyses of RCTs, and 96 associations were described in meta-analyses of cohort studies. Among meta-analyses of RCTs, 14 of the 60 associations were nominally statistically significant (P ≤ .05); no associations between hormonal contraceptive use and adverse outcomes were supported by high-quality evidence. The association between the use of a levonorgestrel-releasing intrauterine system and reductions in endometrial polyps associated with tamoxifen use (odds ratio [OR], 0.22; 95% CI, 0.13-0.38) was graded as having high-quality evidence, and this evidence ranking was retained in the subgroup analysis. Among meta-analyses of cohort studies, 40 of the 96 associations were nominally statistically significant; however, no associations between hormonal contraceptive use and adverse outcomes were supported by convincing evidence in the primary and subgroup analyses. The risk of venous thromboembolism among those using vs not using oral contraception (OR, 2.42; 95% CI, 1.76-3.32) was initially supported by highly suggestive evidence, but this evidence was downgraded to weak in the sensitivity analysis.Conclusions and relevanceThe results of this umbrella review supported preexisting understandings of the risks and benefits associated with hormonal contraceptive use. Overall, the associations between hormonal contraceptive use and cardiovascular risk, cancer risk, and other major adverse health outcomes were not supported by high-quality evidence.
| S-EPMC8760614 | biostudies-literature
Project description:The aim of this study was to review the effects of vitamin D supplementation on depressive symptoms in randomized controlled trials. Although low vitamin D levels have been observationally associated with depressive symptoms, the effect of vitamin D supplementation as an antidepressant remains uncertain.MEDLINE, CINAHL, AMED, PsycINFO, Scopus, The Cochrane Library, and references of included reports (through May 2013) were searched. Two independent reviewers identified and extracted data from randomized trials that compared the effect of vitamin D supplementation on depressive symptoms to a control condition. Two additional reviewers assessed study quality using The Cochrane Risk of Bias Tool. Seven trials (3191 participants) were included.Vitamin D supplementation had no overall effect on depressive symptoms (standardized mean difference [SMD], 0.14; 95% confidence interval [CI], -0.33 to 0.05, p = .16), although considerable heterogeneity was observed. Subgroup analysis showed that vitamin D supplementation for participants with clinically significant depressive symptoms or depressive disorder had a moderate, statistically significant effect (2 studies: SMD, -0.60; 95% CI, -1.19 to -0.01; p = .046), but a small, nonsignificant effect for those without clinically significant depression (5 studies: SMD, -0.04; 95% CI, -0.20 to 0.12; p = .61). Most trials had unclear or high risk of bias. Studies varied in the amount, frequency, duration, and mode of delivery of vitamin D supplementation.Vitamin D supplementation may be effective for reducing depressive symptoms in patients with clinically significant depression; however, further high-quality research is needed.
| S-EPMC4008710 | biostudies-literature
Project description:BackgroundThe evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies.MethodsWe updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features.FindingsWe identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1·40, 95% CI 1·16-1·69). This risk was lower in the eight studies done in women in the general population (pooled HR 1·31, 95% CI 1·10-1·57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I(2) 51·1%, 95% CI 0-79·3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection (I(2) 54%, 0-88·7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1·00, 0·86-1·16) or five studies of norethisterone enanthate (pooled HR 1·10, 0·88-1·37).InterpretationOur findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive.FundingNone.
| S-EPMC4526270 | biostudies-literature
Project description:BACKGROUND/OBJECTIVES:Experiments in animal models have shown a positive association between in utero exposure to pharmacologic sex hormones and offspring obesity. The developmental effects of such hormones on human obesity are unknown. SUBJECTS/METHODS:Using data from a large, prospective pregnancy cohort study (n=19?652), with linkage to a national prescription registry, we evaluated the association between use of hormonal contraceptives before and after conception (defined from dispensed prescription data and characterized by last date of use relative to conception, 12 to >4 months before (n=3392), 4 to >1 months before (n=2541), 1 to >0 months before (n=2997) and 0-12 weeks after (n=567)) in relation to offspring overweight or obesity at age 3 years. RESULTS:We observed a weak, inverse association between early pregnancy use of a combination oral contraceptive and offspring overweight or obesity at age 3 (adjusted odds ratio (OR): 0.75, 95% confidence interval (CI): 0.53, 1.08) and a positive, but imprecise, association with use of a progestin-only oral contraceptive in early pregnancy (adjusted OR: 1.26, 95% CI: 0.79, 2.02). In general, no association was observed between the use of a hormonal contraceptive before conception and offspring overweight or obesity. A sensitivity analysis comparing combination oral contraceptive users in early pregnancy to other unplanned pregnancies without hormonal contraceptive use further strengthened the inverse association (adjusted OR: 0.70, 95% CI: 0.48, 1.02). Other sensitivity analyses were conducted to evaluate the robustness of the associations observed given varying assumptions. CONCLUSIONS:Pharmacologic sex hormones in early pregnancy may be inversely or positively associated with offspring overweight or obesity at age 3, depending on the specific formulation used. The present study provides support for the potential for environmental sources of hormonally active agents to exert developmental effects.
| S-EPMC4365991 | biostudies-literature
Project description:To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users' saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.
| S-EPMC9816169 | biostudies-literature
Project description:OBJECTIVE:Randomised controlled trials (RCT) are the gold standard to provide unbiased data. However, when patients have a treatment preference, randomisation may influence participation and outcomes (eg, external and internal validity). The aim of this study was to assess the influence of patients' preference in RCTs by analysing partially randomised patient preference trials (RPPT); an RCT and preference cohort combined. DESIGN:Systematic review and meta-analyses. DATA SOURCES:MEDLINE, Embase, PsycINFO and the Cochrane Library. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:RPPTs published between January 2005 and October 2018 reporting on allocation of patients to randomised and preference cohorts were included. DATA EXTRACTION AND SYNTHESIS:Two independent reviewers extracted data. The main outcomes were the difference in external validity (participation and baseline characteristics) and internal validity (lost to follow-up, crossover and the primary outcome) between the randomised and the preference cohort within each RPPT, compared in a meta-regression using a Wald test. Risk of bias was not assessed, as no quality assessment for RPPTs has yet been developed. RESULTS:In total, 117 of 3734 identified articles met screening criteria and 44 were eligible (24 873 patients). The participation rate in RPPTs was >95% in 14 trials (range: 48%-100%) and the randomisation refusal rate was >50% in 26 trials (range: 19%-99%). Higher education, female, older age, race and prior experience with one treatment arm were characteristics of patients declining randomisation. The lost to follow-up and cross-over rate were significantly higher in the randomised cohort compared with the preference cohort. Following the meta-analysis, the reported primary outcomes were comparable between both cohorts of the RPPTs, mean difference 0.093 (95% CI -0.178 to 0.364, p=0.502). CONCLUSIONS:Patients' preference led to a substantial proportion of a specific patient group refusing randomisation, while it did not influence the primary outcome within an RPPT. Therefore, RPPTs could increase external validity without compromising the internal validity compared with RCTs. PROSPERO REGISTRATION NUMBER:CRD42019094438.
| S-EPMC6797441 | biostudies-other