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The Cochrane Database of Systematic... Apr 2018Heavy menstrual bleeding (HMB) is an important physical and social problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which are designed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is an important physical and social problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which are designed to reduce bleeding by inhibiting clot-dissolving enzymes in the endometrium.Historically, there has been some concern that using the antifibrinolytic tranexamic acid (TXA) for HMB may increase the risk of venous thromboembolic disease. This is an umbrella term for deep venous thrombosis (blood clots in the blood vessels in the legs) and pulmonary emboli (blood clots in the blood vessels in the lungs).
OBJECTIVES
To determine the effectiveness and safety of antifibrinolytic medications as a treatment for heavy menstrual bleeding.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and two trials registers in November 2017, together with reference checking and contact with study authors and experts in the field.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing antifibrinolytic agents versus placebo, no treatment or other medical treatment in women of reproductive age with HMB. Twelve studies utilised TXA and one utilised a prodrug of TXA (Kabi).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary review outcomes were menstrual blood loss (MBL), improvement in HMB, and thromboembolic events.
MAIN RESULTS
We included 13 RCTs (1312 participants analysed). The evidence was very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding, and poor reporting of study methods), imprecision and inconsistency.Antifibrinolytics (TXA or Kabi) versus no treatment or placeboWhen compared with a placebo, antifibrinolytics were associated with reduced mean blood loss (MD -53.20 mL per cycle, 95% CI -62.70 to -43.70; I² = 8%; 4 RCTs, participants = 565; moderate-quality evidence) and higher rates of improvement (RR 3.34, 95% CI 1.84 to 6.09; 3 RCTS, participants = 271; moderate-quality evidence). This suggests that if 11% of women improve without treatment, 43% to 63% of women taking antifibrinolytics will do so. There was no clear evidence of a difference between the groups in adverse events (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, participants = 297; low-quality evidence). Only one thromboembolic event occurred in the two studies that reported this outcome.TXA versus progestogensThere was no clear evidence of a difference between the groups in mean blood loss measured using the Pictorial Blood Assessment Chart (PBAC) (MD -12.22 points per cycle, 95% CI -30.8 to 6.36; I² = 0%; 3 RCTs, participants = 312; very low quality evidence), but TXA was associated with a higher likelihood of improvement (RR 1.54, 95% CI 1.31 to 1.80; I² = 32%; 5 RCTs, participants = 422; low-quality evidence). This suggests that if 46% of women improve with progestogens, 61% to 83% of women will do so with TXA.Adverse events were less common in the TXA group (RR 0.66, 95% CI 0.46 to 0.94; I² = 28%; 4 RCTs, participants = 349; low-quality evidence). No thromboembolic events were reported in any group.TXA versus non-steroidal anti-inflammatory drugs (NSAIDs)TXA was associated with reduced mean blood loss (MD -73.00 mL per cycle, 95% CI -123.35 to -22.65; 1 RCT, participants = 49; low-quality evidence) and higher likelihood of improvement (RR 1.43, 95% CI 1.18 to 1.74; 1 = 0%; 2 RCTs, participants = 161; low-quality evidence). This suggests that if 61% of women improve with NSAIDs, 71% to 100% of women will do so with TXA. Adverse events were uncommon and no comparative data were available. No thromboembolic events were reported.TXA versus ethamsylateTXA was associated with reduced mean blood loss (MD 100 mL per cycle, 95% CI -141.82 to -58.18; 1 RCT, participants = 53; low-quality evidence), but there was insufficient evidence to determine whether the groups differed in rates of improvement (RR 1.56, 95% CI 0.95 to 2.55; 1 RCT, participants = 53; very low quality evidence) or withdrawal due to adverse events (RR 0.78, 95% CI 0.19 to 3.15; 1 RCT, participants = 53; very low quality evidence).TXA versus herbal medicines (Safoof Habis and Punica granatum)TXA was associated with a reduced mean PBAC score after three months' treatment (MD -23.90 pts per cycle, 95% CI -31.92 to -15.88; I² = 0%; 2 RCTs, participants = 121; low-quality evidence). No data were available for rates of improvement. TXA was associated with a reduced mean PBAC score three months after the end of the treatment phase (MD -10.40 points per cycle, 95% CI -19.20 to -1.60; I² not applicable; 1 RCT, participants = 84; very low quality evidence). There was insufficient evidence to determine whether the groups differed in rates of adverse events (RR 2.25, 95% CI 0.74 to 6.80; 1 RCT, participants = 94; very low quality evidence). No thromboembolic events were reported.TXA versus levonorgestrel intrauterine system (LIUS)TXA was associated with a higher median PBAC score than TXA (median difference 125.5 points; 1 RCT, participants = 42; very low quality evidence) and a lower likelihood of improvement (RR 0.43, 95% CI 0.24 to 0.77; 1 RCT, participants = 42; very low quality evidence). This suggests that if 85% of women improve with LIUS, 20% to 65% of women will do so with TXA. There was insufficient evidence to determine whether the groups differed in rates of adverse events (RR 0.83, 95% CI 0.25 to 2.80; 1 RCT, participants = 42; very low quality evidence). No thromboembolic events were reported.
AUTHORS' CONCLUSIONS
Antifibrinolytic treatment (such as TXA) appears effective for treating HMB compared to placebo, NSAIDs, oral luteal progestogens, ethamsylate, or herbal remedies, but may be less effective than LIUS. There were too few data for most comparisons to determine whether antifibrinolytics were associated with increased risk of adverse events, and most studies did not specifically include thromboembolism as an outcome.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antifibrinolytic Agents; Ethamsylate; Female; Hemostatics; Humans; Intrauterine Devices, Medicated; Lythraceae; Menorrhagia; Norethindrone; Plant Extracts; Progestins; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 29656433
DOI: 10.1002/14651858.CD000249.pub2 -
Menopause (New York, N.Y.) 2005There is a rapidly evolving debate on the indications and appropriate duration of therapy for postmenopausal hormone therapy. The objective of this meta-analysis was to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
There is a rapidly evolving debate on the indications and appropriate duration of therapy for postmenopausal hormone therapy. The objective of this meta-analysis was to examine the specific relationships of postmenopausal estrogen therapy (ET), postmenopausal combined (estrogen-progestogen) hormone therapy (CHT), and the incidence of breast cancer.
DESIGN
We performed computerized searches of MEDLINE and CancerLit through September 2003 and reviewed reference lists of retrieved studies and meta-analyses. We included English-language studies that identified noncontraceptive postmenopausal hormone use; reported on the risks of "current use" of ET and/or CHT and breast cancer incidence; were case-control, cohort, or experimental; and reported either an odds ratio (OR), relative risk (RR), or HR with CIs. Two investigators were involved during all stages of study selection and independently extracted all data selected for inclusion in meta-analyses.
RESULTS
Meta-analysis of 13 studies of ET and breast cancer (700,000 women) resulted in an OR of 1.16 (95% confidence limits [CL] 1.06, 1.28), with estimates for less than 5 years use 1.16 (1.02, 1.32) and more than 5 years use 1.20 (1.06, 1.37). Meta-analysis of eight studies of CHT and breast cancer (650,000 women) resulted in an OR of 1.39 (95% CL 1.12, 1.72), with estimates for less than 5 years use 1.35 (1.16, 1.57) and more than 5 years use 1.63 (1.22, 2.18).
CONCLUSIONS
Data from observational studies support the association of increased but considerably different risks for breast cancer incidence among current users of ET and CHT. These represent the first pooled estimates for ET. CHT estimates correspond to those from randomized trials.
Topics: Breast Neoplasms; Estrogen Replacement Therapy; Female; Humans; Incidence; Postmenopause; Progestins; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 16278609
DOI: 10.1097/01.gme.0000184221.63459.e1 -
Cephalalgia : An International Journal... Apr 2018Background Migraine is highly prevalent in women (18%). Peak morbidity affects their most productive years, coinciding with peak fertility. Hormonal contraception is... (Meta-Analysis)
Meta-Analysis
Background Migraine is highly prevalent in women (18%). Peak morbidity affects their most productive years, coinciding with peak fertility. Hormonal contraception is often tailored for migraine prevention. Estrogen-containing contraceptives may be contraindicated in women experiencing migraine with aura due to the risk of vascular events. While improvements in migraine with a progestin-only pill (POP), which inhibits ovulation are documented, the strength and quality of evidence has not been formally evaluated. Objectives To determine the effectiveness of progestin-only contraceptives for migraine treatment by systematic review and meta-analysis. Data sources and selection MEDLINE, EMBASE and Cochrane Libraries were searched (1980 to September 2016) for studies on progestin-only treatments for migraine. Studies in English on >4 non-menopausal women aged 18-50 with migraine diagnosed by formal criteria were included. Data extraction and analysis Data were quality-assessed using the GRADE system. A random effects model was used for pooled analyses. Results Pooled analyses of four studies demonstrated that desogestrel 75 mcg/day, POP significantly but modestly reduced the number of migraine attacks and migraine days. Reduced intensity and duration, reduced analgesic and triptan use were observed, along with improved headache-related quality of life. GRADE analysis indicated evidence was low to very low for each outcome measure. Adverse effects resulted in treatment cessation for <10% of participants. Two studies compared desogestrel POP to a combined oral contraceptive, demonstrating similar migraine outcomes for both treatments. Conclusions The desogestrel POP shows promise in improving migraine in women. Current evidence is observational and based on small samples of women using only one oral progestin-only formulation. Further randomized trials on additional progestin-only contraceptives are required to confirm their role in migraine management.
Topics: Adolescent; Adult; Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Migraine Disorders; Progestins; Young Adult
PubMed: 28554244
DOI: 10.1177/0333102417710636 -
Breast Cancer Research and Treatment Aug 2020Hormone replacement therapy (HRT) is used to reduce climacteric symptoms of menopause and prevent osteoporosis; however, it increases risk of breast cancer. Mammographic...
PURPOSE
Hormone replacement therapy (HRT) is used to reduce climacteric symptoms of menopause and prevent osteoporosis; however, it increases risk of breast cancer. Mammographic density (MD) is also a strong risk factor for breast cancer. We conducted this review to investigate the association between HRT use and MD and to assess the effect of different HRT regimens on MD.
METHODS
Two of authors examined articles published between 2002 and 2019 from PubMed, Embase, and OVID using Covidence systematic review platform. Any disagreements were discussed until consensus was reached. The protocol used in this review was created in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality of each eligible study was assessed using the Oxford Center for Evidence-Based Medicine (OCEBM) hierarchy.
RESULTS
Twenty-two studies met the inclusion criteria. Six studies showed that using estrogen plus progestin (E + P) HRT was associated with higher MD than estrogen alone. Four studies reported that continuous estrogen plus progestin (CEP) users had higher MD than sequential estrogen plus progestin (SEP) and estrogen alone users. However, two studies showed that SEP users had slightly higher MD than CEP users and estrogen alone users.
CONCLUSIONS
Epidemiological evidence is rather consistent suggesting that there is a positive association between HRT use and MD with the highest increase in MD among current users, and CEP users. Our results suggest that due to increase in MD and masking effect, current E + P users may require additional screening procedures, shorter screening intervals, or using advanced imaging techniques.
Topics: Breast Density; Breast Neoplasms; Female; Hormone Replacement Therapy; Humans; Risk Factors
PubMed: 32572713
DOI: 10.1007/s10549-020-05744-w -
Cancer Management and Research 2019This study aimed to identify potential prognostic factors for patients with complex atypical hyperplasia (CAH) or early-stage endometrial cancer (EC) who received...
Weight control is vital for patients with early-stage endometrial cancer or complex atypical hyperplasia who have received progestin therapy to spare fertility: a systematic review and meta-analysis.
This study aimed to identify potential prognostic factors for patients with complex atypical hyperplasia (CAH) or early-stage endometrial cancer (EC) who received progestin therapy to spare fertility and, thus, improve the management of this patient group. The PubMed, PMC, EMBASE, Web of Science, and Cochrane databases were searched for correlational studies published in English. Studies that evaluated the prognosis of patients with CAH or early-stage EC were pooled for a systematic review and meta-analysis. In total, 31 eligible studies, including 8 prospective and 23 retrospective studies involving 1099 patients, were included in this analysis. The most commonly used progestin agents were medroxyprogesterone acetate (MPA, 47.0%) and megestrol acetate (MA, 25.5%). The total complete response (CR) rate was 75.8% (833/1099), and the median time to CR with first-line progestin therapy was 6 months. In total, 294 (26.8%) patients who achieved CR became pregnant spontaneously (28 cases) or through assisted reproductive technology (127 cases). During the median follow-up of 39 months, 245 (22.3%) women developed recurrence. Only one patient (0.09%) died of the disease. The meta-analysis showed that compared to a BMI<25 kg/m and CAH, a body mass index (BMI) ≥25 kg/m (=0.0004, odds ratios (OR), 0.4; 95% confidence interval, 0.3-0.6) and EC (=0.0000, OR, 0.3; 95% confidence interval, 0.2-0.6) were significantly associated with a higher likelihood of a CR. Patients with a BMI≥25 kg/m (=0.0007, OR, 2.5; 95% confidence interval, 1.4-4.3), PCOS (=0.0006, OR, 3.4; 95% confidence interval, 1.5-7.9), and EC (=0.0344, OR, 2.8; 95% confidence interval, 1.4-5.3) had a significantly higher risk of recurrence. In general, patients with CAH or early-stage EC who were treated with progesterone therapy had a favorable prognosis. However, the recurrence risk was not insignificant. Weight control is crucial for improving the clinical management of this patient group.
PubMed: 31190979
DOI: 10.2147/CMAR.S194607 -
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 -
JMIR Research Protocols Apr 2018Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through... (Review)
Review
Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis.
BACKGROUND
Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis.
OBJECTIVE
This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS.
METHODS
We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone-binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot.
RESULTS
COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=-0.48; 95% CI -0.81 to -0.15), 6 months (WMD=-2.33; 95% CI -3.48 to -1.18), and 12 months (WMD=-4.70; 95% CI -4.98 to -4.42) and a decrease in LH levels after 3 months (WMD=-3.57; 95% CI -5.14 to -1.99), 6 months (WMD=-5.68; 95% CI -9.57 to -1.80), and 12 months (WMD=-11.60; 95% CI -17.60 to -5.60). Use of COCs containing drospirenone for 6 months decreased FSH (WMD=-0.93; 95% CI -1.79 to -0.08) and LH (WMD=-4.59; 95% CI -7.53 to -1.66) levels. Data for products containing desogestrel were few, but this compound generally had no statistically significant influence on gonadotropin levels similar to that observed with COCs containing cyproterone acetate and drospirenone. Use of COCs was not associated with any significant change in LH-to-FSH ratio. COCs containing cyproterone acetate showed maximum effect on gonadotropin suppression. COCs containing cyproterone acetate significantly decreased estradiol concentrations, whereas those containing drospirenone exhibited no such effect. All COCs demonstrated improvement in androgenic profile and had the same effects on total testosterone and sex hormone-binding globulin concentrations. Progestin compound and treatment duration had no statistically significant effects on changing total testosterone and sex hormone-binding globulin levels.
CONCLUSIONS
COCs containing cyproterone acetate can effectively suppress gonadotropins, leading to a decrease in androgenic parameters. Although different products of COCs could significantly suppress the androgenic profile, it seems that products containing cyproterone acetate are more effective in suppressing gonadotropin and estradiol levels in patients with PCOS.
PubMed: 29695378
DOI: 10.2196/resprot.9024 -
BMJ (Clinical Research Ed.) Aug 2012To evaluate the risk of venous thromboembolic events associated with the use of progestin-only contraception and whether that risk differs with the mode of drug delivery... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the risk of venous thromboembolic events associated with the use of progestin-only contraception and whether that risk differs with the mode of drug delivery (oral, intrauterine, or depot injection).
DESIGN
Systematic review and meta-analysis of randomised controlled trials and observational studies.
DATA SOURCES
Pubmed, Embase, Cochrane Library, and reference lists of relevant reviews.
STUDY SELECTION
Randomised controlled trials and case-control, cohort, and cross sectional studies with venous thromboembolic outcome for progestin-only contraception reported relative to a non-hormone comparator group.
DATA EXTRACTION
Data were extracted by two independent investigators, and consensus for inclusion was reached after assessment by additional investigators.
RESULTS
Among the 2022 unique references identified by all searches, eight observational studies fulfilled inclusion criteria. A total of 147 women across all studies were diagnosed with a venous thromboembolic event while taking progestin-only contraception, and the summary measure for the adjusted relative risk of a venous thromboembolic episode for users versus non-users of a progestin-only contraceptive was, based on the random effects model, 1.03 (95% CI 0.76 to 1.39). Subgroup analysis confirmed there was no association between venous thromboembolic risk and progestin-only pills (relative risk 0.90 (0.57 to 1.45)) or a progestin intrauterine device (0.61 (0.24 to 1.53)). The relative risk of a venous thromboembolic event for users of an injectable progestin versus non-users was 2.67 (1.29 to 5.53).
CONCLUSIONS
Published data assessing the risk of venous thromboembolism in women prescribed progestin-only contraception are limited. In this meta-analysis of eight observational studies, the use of progestin-only contraception was not associated with an increased risk of venous thromboembolism compared with non-users of hormonal contraception. The potential association between injectable progestins and thrombosis requires further study.
Topics: Administration, Oral; Contraceptive Agents, Female; Delayed-Action Preparations; Epidemiologic Methods; Female; Humans; Intrauterine Devices, Medicated; Progestins; Venous Thromboembolism
PubMed: 22872710
DOI: 10.1136/bmj.e4944 -
Medicine Sep 2017There are some fertility-sparing treatments in patients with early endometrial cancer (EEC) or atypical complex hyperplasia (ACH), and the objective is to compare them... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are some fertility-sparing treatments in patients with early endometrial cancer (EEC) or atypical complex hyperplasia (ACH), and the objective is to compare them by evaluating the oncologic and reproductive outcomes.
METHODS
We searched the published literature using Medline, Cochrane, EMBASE, and Google Scholar databases up to January 3, 2017, with various combinations of keywords fertility-sparing treatments, progesterone, progestin, intrauterine devices, early endometrial cancer, and atypical complex hyperplasia. The primary endpoint is the complete response (CR) rate, and the secondary endpoints are the partial response (PR) rate, relapse rate (RR), pregnancy rate, and live birth rate.
RESULTS
Twenty-eight studies containing 1038 women with EEC or ACH were included for review and meta-analysis. The results demonstrated that women with EEC or ACH managed with progestin had a pooled CR rate of 71% (95% confidence interval [CI]: 63-77%). The pooled pregnancy outcomes showed that 34% of women taking progestin treatment for EEC or ACH became pregnant (95% CI: 30-38%); however, only 20% of them delivered live newborns. The pooled CR rate for women using intrauterine device (IUD) was 76% (95% CI: 67-83%), and pooled RR was 9% (95% CI: 5-17%). The pregnancy rate for women whom underwent IUD was 18% (95% CI: 7-37%), and 14% of them delivered live newborns. In patients using progestin plus IUD, the pooled CR rate was 87% (95% CI: 75-93%); among those patients, 40% became pregnant (95% CI: 20-63%), and 35% delivered live newborns. There is no publication bias for the CR rate.
CONCLUSION
For patients with EEC and ACH, treatments with progestin, with or without IUD, or IUD alone can reach good CR rate; however, the pregnancy outcomes might be worse in patients treated with IUD alone. Further randomized-controlled studies are warranted to find out a better solution.
Topics: Endometrial Neoplasms; Female; Fertility Preservation; Humans; Hyperplasia; Organ Sparing Treatments; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 28906392
DOI: 10.1097/MD.0000000000008034 -
Frontiers in Cardiovascular Medicine 2023The use of oral contraceptives (OCs) is associated with an increased risk of cardiovascular events such as arterial and venous thrombosis (VTE). Cardiovascular diseases... (Review)
Review
BACKGROUND
The use of oral contraceptives (OCs) is associated with an increased risk of cardiovascular events such as arterial and venous thrombosis (VTE). Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with low- and middle-income nations accounting for over three-quarter of CVD deaths. The aim of this systematic review is to provide a comprehensive synthesis of the available evidence on the link between OC use and CVD risk in premenopausal women and to further assess the role of geographic disparities in the reported prevalence of CVD risk in women on OCs.
METHODS
A comprehensive search of databases such as MEDLINE, Academic Search Complete, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Health Source: Nursing/Academic Edition was conducted, right from the inception to the present, by using the EBSCOhost search engine. The Cochrane Central Register of Clinical trials (CENTRAL) was also searched to augment relevant sources of information. OpenGrey, which is a repository of information providing open access to bibliographical references, was searched and the reference list of the selected studies was also scanned. The potential risk of bias of the included studies was assessed using the modified Downs and Black checklist. Data analysis was performed using the Review Manager (RevMan) version 5.3.
RESULTS
We included 25 studies that comprised 3,245 participants, of which 1,605 (49.5%) are OC users, while 1,640 (50.5%) are non-OC users. A total of 15 studies were included for meta-analysis, and the overall pooled estimates suggested a significant increase in the traditional cardiovascular risk variables [standardized mean difference (SMD) = 0.73, (0.46, 0.99) ( = 5.41, < 0.001)] and little to no difference in endothelial activation among OC users when compared with non-OC users [SMD = -0.11, (-0.81, 0.60) ( = 0.30, = 0.76)]. Europe [SMD = 0.03, (-0.21, 0.27), ( = 0.25 = 0.88)] had the least effect size, while North America had the highest effect size [SMD = 1.86, (-0.31, 4.04), ( = 1.68 = 0.09)] for CVD risk in OC users when compared with non-OC users.
CONCLUSION
The use of OCs suggests a significant increase in the prevalence of traditional cardiovascular risk variables with little to no difference in the risk of endothelial dysfunction when compared with non-OC users, and the magnitude of CVD risks varies across different geographical regions.
REGISTRATION AND PROTOCOL
This systematic review was registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD42020216169.
PubMed: 37180788
DOI: 10.3389/fcvm.2023.1127104