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Oral Contraceptive Use and Increased Risk of Stroke: A Dose-Response Meta-Analysis of Observational Studies.

ABSTRACT: Background: Oral contraceptive (OCP) use might increase the risk of stroke in women. We examined a possible dose-response relation between OCP use and the risk of stroke in young and middle-aged women. Methods: A retrieval of PubMed and EMBASE databases was performed. We selected observational studies that reported odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of stroke in OCP users. A two-stage dose-response analysis was conducted using the random-effects model and the restricted spline model. Results: A total of 6 cohort studies and 12 case-control studies were included, which involved 2,143,174 participants and 11,661 cases of stroke including ischemic stroke (IS), hemorrhagic stroke (HS), and stroke of unknown origin. The pooled ORs of total stroke were 1.19 (95% CI, 1.16-1.23) for every 10-?g increment in estrogen dosage, 1.20 (95% CI, 1.05-1.37) for every 5-years increment in duration of OCP use, and 0.82 (95% CI, 0.68-0.98) for every 5-years increment in duration of OCP cessation. The ORs of IS were 1.20 (95% CI, 1.17-1.22) in estrogen dosage, 1.24 (95% CI, 1.04-1.49) in duration of OCP use, and 0.78 (95% CI, 0.67-0.92) in duration of OCP cessation. The ORs of HS were 1.10 (95% CI, 1.04-1.16) in estrogen dosage, 1.13 (95% CI, 0.93-1.36) in duration of OCPs, and 0.71 (95% CI, 0.55-0.92) in duration of OCP cessation. The pooled ORs of total stroke from prospective studies (1.12; 95% CI, 1.01-1.24) were lower than those from retrospective studies (1.30; 95% CI, 1.01-1.67). Conclusions: The higher estrogen dosage significantly increased the risks of total stroke, IS, and HS, respectively. The longer duration of OCP use significantly increased the risks of total stroke and IS, but its effects on HS risk were marginal. The longer duration of OCP cessation significantly decreased the risks of total stroke, IS, and HS, respectively. These findings affirm the contribution of estrogen dose and duration of OCP use to the increased risk of stroke, which may be critical for the instruction of OCP use and the prevention and management of cerebrovascular diseases.

SUBMITTER: Li F

PROVIDER: S-EPMC6767325 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Oral Contraceptive Use and Increased Risk of Stroke: A Dose-Response Meta-Analysis of Observational Studies.

Li Feng F Zhu Lin L Zhang Jie J He Hongye H Qin Yueqi Y Cheng Yuan Y Xie Zongyi Z

Frontiers in neurology 20190923

<b>Background:</b> Oral contraceptive (OCP) use might increase the risk of stroke in women. We examined a possible dose-response relation between OCP use and the risk of stroke in young and middle-aged women. <b>Methods:</b> A retrieval of PubMed and EMBASE databases was performed. We selected observational studies that reported odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of stroke in OCP users. A two-stage dose-response analysis was conducted using the random-effects mode ...[more]

PMID: 31592249

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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.

Project description:ObjectiveData regarding the use and effect of hormonal contraceptives on bone mass acquisition during adolescence are contradictory. The present study was designed to evaluate bone metabolism in two groups of healthy adolescents using combined oral contraceptives (COC).MethodsA total of 168 adolescents were recruited from 2014 to 2020 in a non-randomized clinical trial and divided into three groups. The COC1 group used 20 μg Ethinylestradiol (EE)/150 μg Desogestrel and the COC2 group used 30 μg EE/3 mg Drospirenone over a period of two years. These groups were compared to a control group of adolescent non-COC users. The adolescents were submitted to bone densitometry by dual-energy X-ray absorptiometry and measurement of bone biomarkers, bone alkaline phosphatase (BAP), and osteocalcin (OC) at baseline and 24 months after inclusion in the study. The three groups studied were compared at the different time points by ANOVA, followed by Bonferroni's multiple comparison test.ResultsIncorporation of bone mass was greater in non-users at all sites analyzed (4.85 g in lumbar Bone mineral content (BMC)) when compared to adolescents of the COC1 and COC2 groups, with a respective increase of 2.15 g and loss of 0.43g in lumbar BMC (P = 0.001). When comparing subtotal BMC, the control increased 100.83 g, COC 1 increased 21.46 g, and COC 2 presented a reduction of 1.47 g (P = 0.005). The values of bone markers after 24 months are similar for BAP, being 30.51 U/L (± 11.6) for the control group, 34.95 U/L (± 10.8) for COC1, and 30.29 U/L for COC 2 (± 11.5) (P = 0.377). However, when we analyzed OC, we observed for control, COC 1, and COC 2 groups, respectively, 13.59 ng/mL (± 7.3), 6.44 ng/mL (± 4.6), and 9.48 ng/mL (± 5.9), with P = 0.003. Despite loss to follow-up occurring in the three groups, there were no significant differences between the variables in adolescents at baseline who remained in the study during the 24-month follow-up and those who were excluded or lost to follow-up.ConclusionBone mass acquisition was compromised in healthy adolescents using combined hormonal contraceptives when compared to controls. This negative impact seems to be more pronounced in the group that used contraceptives containing 30 μg EE.Clinical trial registrationhttp://www.ensaiosclinicos.gov.br, RBR-5h9b3c. "Low-dose combined oral contraceptive use is associated with lower bone mass in adolescents".

Project description:BackgroundAssociations between endogenous estrogen exposure indicators and risk of subtypes of dementia have been unclear.MethodsDatabases (PubMed, EMBASE and Web of Science) were searched electronically on 1st July and updated regularly until 12nd November 2021. Observational studies of English language were selected if reported an effect estimate [e.g., odds ratio (OR), rate ratio (RR) or hazard ratio (HR)] and 95% CI for the association between any exposure (age of menarche, age at menopause, reproductive period, estradiol level) and any endpoint variable [all-cause dementia, Alzheimer's disease (AD), vascular dementia (VD), cognitive impairment (CI)]. Random-effects models and dose-response meta-analyses were used to calculate estimates and to show the linear/nonlinear relationship. PROSPERO CRD42021274827.FindingsWe included 22 studies (475 9764 women) in this analysis. We found no clear relationship between late menarche (≥14 vs <14 years) and dementia, CI in categorical meta-analysis compared to a J-shape relationship in dose-response meta-analyses. Later menopause (≥45 vs <45 years) was consistently associated with a lower risk of all-cause dementia (pooled RR: 0.87, 95%CI: 0.78-0.97, I2=56.0%), AD (0.67, 0.44-0.99, I2=78.3%), VD (0.87, 0.80-0.94) and CI (0.82, 0.71-0.94, I2=19.3%) in categorical meta-analysis, showing similar results in dose-response meta-analyses. An inverse relationship between longer reproductive duration (≥35 vs <35 years) and dementia was observed in dose-response meta-analysis. In addition, estradiol levels after menopause were inversely correlated with the risk of AD and CI.InterpretationIn this study, later menopause and longer reproductive period were associated with a lower risk of dementia, while the relationship for menarchal age was J-shaped. There was an inverse relationship between higher postmenopausal estrogen levels and risk of AD and CI. Longitudinal study are needed to further explore the association between life-time estrogen exposure and risk of subtypes of dementia.FundingStart-up Foundation for Scientific Research in Shandong University.

Dataset Information

Oral Contraceptive Use and Increased Risk of Stroke: A Dose-Response Meta-Analysis of Observational Studies.

Publications

Oral Contraceptive Use and Increased Risk of Stroke: A Dose-Response Meta-Analysis of Observational Studies.

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