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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 -
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 -
Pharmacotherapy Feb 2022Hormonal contraceptives have been used in perimenopausal women to manage a variety of symptoms and prevent unintended pregnancy. However, it is unclear what... (Review)
Review
Hormonal contraceptives have been used in perimenopausal women to manage a variety of symptoms and prevent unintended pregnancy. However, it is unclear what contraceptive regimen is best for these women. To evaluate hormonal contraceptive methods in women experiencing perimenopause using two prespecified outcomes: perimenopausal symptom management and long-term effects. A literature search of PubMed and EMBASE databases was performed (January 1990 to October 2021) using search terms "perimenopause" and "contraception." Relevant full-text articles in English were included. Fifteen clinical articles were reviewed: Fourteen were internationally based, and one study was conducted in the United States. Nine articles evaluated symptom resolution, and six of these nine reported statistically significant changes in favor of treating perimenopausal women with hormonal contraceptives compared with no treatment. Seven studies evaluated long-term outcomes including bone loss and metabolic parameters, and six of these seven showed statistically significant improvements with hormonal contraceptives. Based on limited data and a lack of comparative studies, the use of a levonorgestrel intrauterine device with supplemental low-dose menopausal estrogen has positive results for the management of disruptive perimenopausal symptoms and long-term outcomes. Hormonal contraception in perimenopausal women improves symptom management and long-term outcomes if patients do not have contraindications. When selecting a contraceptive for women in perimenopause, clinicians and pharmacists need to address specific patient risk factors, symptom profiles, long-term risks and benefits, and patient preferences.
Topics: Contraception; Contraceptive Agents; Female; Humans; Menopause; Perimenopause; Pregnancy; Risk Factors
PubMed: 34967466
DOI: 10.1002/phar.2657 -
Frontiers in Neuroendocrinology Apr 2023In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter...
In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.
Topics: Animals; Humans; Progestins; Progesterone; Contraceptive Agents; Cross-Sectional Studies; Progesterone Congeners; Brain
PubMed: 36758768
DOI: 10.1016/j.yfrne.2023.101060 -
Women's Health (London, England) 2022Implanon discontinuation before the recommended time is problematic, as it puts women at risk of unwanted pregnancies and unsafe abortions, along with negative maternal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Implanon discontinuation before the recommended time is problematic, as it puts women at risk of unwanted pregnancies and unsafe abortions, along with negative maternal health outcomes. Although the magnitude and determinants of Implanon discontinuation have been studied in Ethiopia, the results were inconsistent, with significant variability. Hence, this systematic review and meta-analysis aimed at estimating the pooled prevalence of Implanon discontinuation and its determinants in Ethiopia.
METHODS
A comprehensive search of studies published before 18 February 2022 was done using electronic databases such as PubMed, Embase, Google Scholar, Scopus, Web of Science, Science Direct, and Cochrane Library. The relevant data were extracted using a Microsoft Excel 2013 and analyzed using STATA Version 16. A random-effect meta-analysis model was used to compute pooled prevalence and odds ratio. The Cochrane test statistics and tests were used to assess the heterogeneity of the included studies. A funnel plot, Begg's, and Egger's tests were used to check for the presence of publication bias.
RESULTS
A total of 11 studies with 4320 study participants were included in this meta-analysis. The overall pooled prevalence of Implanon discontinuation in Ethiopia was found to be 32.62% (95% confidence interval = 24.10, 41.13). There was significant heterogeneity among the included studies ( = 97.4%, < 0.001). However, there was no statistical evidence of publication bias ( = 0.533). Dissatisfied with service provision at the time of insertion (odds ratio = 3.92, 95% confidence interval = 1.54, 6.29), not having pre-insertion counseling (odds ratio = 2.98, 95% confidence interval = 1.91, 5.04), the absence of post-insertion follow-up (odds ratio = 4.03, 95% confidence interval = 2.17, 5.90), and the presence of side effects (odds ratio = 2.93, 95% confidence interval = 1.87, 3.98) were found to be determinants of Implanon discontinuation.
CONCLUSION
According to this systematic review and meta-analysis, one-third of Ethiopian women discontinued Implanon before the recommended time (3 years). Program managers and service providers should consider using more evidence-based and participatory counseling approaches to enhance client satisfaction. Furthermore, family planning service delivery points should be equipped to manage and reassure women who are experiencing side effects.
Topics: Black People; Desogestrel; Ethiopia; Female; Humans; Pregnancy; Prevalence
PubMed: 35762596
DOI: 10.1177/17455057221109222 -
Reproductive Biomedicine Online Jun 2022The aim of this systematic review and meta-analysis was to evaluate the effectiveness of different hormone therapies, including hormonal contraceptives, in women with... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review and meta-analysis was to evaluate the effectiveness of different hormone therapies, including hormonal contraceptives, in women with premature ovarian insufficiency (POI). Thirty reports of 28 studies were included, with a total of 4004 participants with POI from diverse aetiologies, of whom 3785 received hormone therapies and 219 received calcium supplementation, vitamin D, placebo or no treatment. Hormone therapy was superior to non-treatment, placebo, calcitriol or calcium in preserving bone mineral density (BMD) in women with POI. Hormone therapy was associated with up to 80% reduction in the prevalence of hot flushes and with stability or improvement in the quality of life scores. Hormone therapy induced significant increases in uterine volume and endometrial thickness in women with POI. The studies yielded convergent results and were of good quality, although some lacked blinding or had incomplete outcome data. Moderate to high quality evidence was found that hormone therapy with oestrogen and progesterone or progestin (including contraceptives) is beneficial to women with POI, not only to mitigate hypoestrogenic symptoms but also to preserve BMD and avoid uterine atrophy. More studies are needed to confirm the long-term safety of this therapy and to assess its possible impact on the risk of hard outcomes such as bone fractures and cardiovascular events.
Topics: Calcium; Contraceptive Agents; Estrogens; Female; Humans; Menopause, Premature; Primary Ovarian Insufficiency; Quality of Life
PubMed: 35461762
DOI: 10.1016/j.rbmo.2022.02.006 -
Human Reproduction (Oxford, England) Apr 2024Does the change in endometrial thickness (EMT) from the end of the follicular/estrogen phase to the day of embryo transfer (ET) determine subsequent pregnancy outcomes? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
Does the change in endometrial thickness (EMT) from the end of the follicular/estrogen phase to the day of embryo transfer (ET) determine subsequent pregnancy outcomes?
SUMMARY ANSWER
Endometrial compaction from the late-proliferative to secretory phase is not associated with live birth rate (LBR) and other pregnancy outcomes.
WHAT IS KNOWN ALREADY
Endometrial compaction has been suggested to be indicative of endometrial responsiveness to progesterone, and its association with ET outcome has been investigated but is controversial.
STUDY DESIGN, SIZE, DURATION
A systematic review with meta-analysis was carried out. PubMed, EMBASE, and Web of Science were searched to identify relevant studies from inception to 18 November 2022. The reference lists of included studies were also manually screened for any additional publications.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Cohort studies comparing ET pregnancy outcomes between patients with and without endometrial compaction were included. A review of the studies for inclusion, data extraction, and quality assessment was performed by two independent reviewers. The effect size was synthesized as odds ratio (OR) with 95% CI using a random-effects model. Heterogeneity and publication bias were assessed by the I2 statistic and Egger's test, respectively. The primary outcome was LBR. Secondary outcomes included biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), miscarriage rate (MR), ongoing pregnancy rate (OPR), and ectopic pregnancy rate (EPR).
MAIN RESULTS AND THE ROLE OF CHANCE
Seventeen cohort studies involving 18 973 ET cycles fulfilled the eligibility criteria. The pooled results revealed that there were no significant differences between endometrial compaction and non-compaction groups in LBR (crude OR (cOR) = 0.95, 95% CI 0.87-1.04; I2 = 0%; adjusted OR (aOR) = 1.02, 95% CI 0.87-1.19, I2 = 79%), BPR (cOR = 0.93, 95% CI 0.81-1.06; I2 = 0%; aOR = 0.88, 95% CI 0.75-1.03, I2 = 0%), CPR (cOR = 0.98, 95% CI 0.81-1.18; I2 = 70%; aOR = 0.86, 95% CI 0.72-1.02, I2 = 13%), MR (cOR = 1.09, 95% CI 0.90-1.32; I2 = 0%; aOR = 0.91, 95% CI 0.64-1.31; I2 = 0%), and EPR (cOR = 0.70, 95% CI 0.31-1.61; I2 = 61%). The OPR was marginally higher in crude analysis (cOR = 1.48, 95% CI 1.01-2.16; I2 = 81%) among women with compacted endometrium, but was not evident in adjusted results (aOR = 1.36, 95% CI 0.86-2.14; I2 = 84%). Consistently, the pooled estimate of LBR remained comparable in further subgroup and sensitivity analyses according to the degree of compaction (0%, 5%, 10%, 15%, or 20%), type of ET (fresh, frozen, or euploid only), and endometrial preparation protocol (natural or artificial). No publication bias was observed based on Egger's test.
LIMITATIONS, REASONS FOR CAUTION
Although the number of included studies is sufficient, data on certain measures, such as EPR, are limited. The inherent bias and residual confounding were also inevitable owing to the observational study design. Furthermore, inconsistent definitions of pregnancy outcomes may affect the accuracy of our pooled analysis.
WIDER IMPLICATIONS OF THE FINDINGS
Given the lack of prognostic value, assessing endometrial compaction or repeated EMT measurement on the day of ET may not be necessary or warranted.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by Natural Science Foundation of Jiangxi Province (20224BAB216025), National Natural Science Foundation of China (82260315), and Central Funds Guiding the Local Science and Technology Development (20221ZDG020071). The authors have no conflicts of interest to declare.
REGISTRATION NUMBER
CRD42022384539 (PROSPERO).
Topics: Pregnancy; Humans; Female; Pregnancy Outcome; Pregnancy Rate; Embryo Transfer; Progesterone; Birth Rate; Abortion, Spontaneous; Pregnancy, Ectopic; Retrospective Studies; Live Birth; Observational Studies as Topic
PubMed: 38323525
DOI: 10.1093/humrep/deae012 -
BMC Medicine Oct 2022Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence.
METHODS
We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples.
RESULTS
We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here.
CONCLUSIONS
Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
Topics: Elafin; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins; Immunologic Factors; Interferons; Interleukin 1 Receptor Antagonist Protein; Interleukin-16; Interleukin-1alpha; Interleukin-6; Interleukins; Lactoferrin; Menstrual Cycle; Muramidase; Progesterone; beta-Defensins
PubMed: 36195867
DOI: 10.1186/s12916-022-02532-9 -
Minerva Medica Feb 2021We conducted a systematic review to evaluate the outcomes and role of ultra-minimally invasive surgical approaches for treatment of women diagnosed with endometrial...
INTRODUCTION
We conducted a systematic review to evaluate the outcomes and role of ultra-minimally invasive surgical approaches for treatment of women diagnosed with endometrial cancer. Although, there is no agreed definition of the term "ultraminimal," we considered the hysteroscopic surgery, single-port surgery, mini/microlaparoscopy and percutaneous laparoscopy as surgical approaches that would best fit this description.
EVIDENCE ACQUISITION
The current systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. We performed a literature search using MEDLINE (PubMed), EMBASE and Cochrane Library databases for English-language studies published before August 1, 2020. We used the following keywords including "endometrial cancer," "endometrial malignancy," "fertility-sparing or preserving," "hysteroscopy," "hysteroscopic resection," "dilatation and curettage," "ultra-minimally invasive surgery," "progestin therapy," "hormone therapy," "single port," "single-site," "minilaparoscopy," "microlaparoscopy," "percutaneous" and "3 mm laparoscopy."
EVIDENCE SYNTHESIS
A total of 21 studies, reporting on 229 patients were included. 219 (95.6%) of the patients were premenopausal. Among premenopausal women, complete disease response was reported in 186 (84.9%) patients. The complete response rate was 77.1% in patients who underwent focal or extensive endometrial resection, 90.9% in patients who had the two-step approach and 88.9% in the group of patients treated with the three-step technique. Among 98 women who wished and attempted to conceive, 65 (66.3%) women became pregnant. Recurrent disease was diagnosed in 26 of 219 (11.9%) patients. No surgical complications were reported. In 10 postmenopausal patients that underwent hysteroscopic resection, no recurrences were detected after 5 years of follow-up. We identified 11 studies that reported on the use single-port laparoscopic surgery and included a total of 447 patients. The rate of intraoperative and postoperative complications was 2.6% and 5.2%, respectively. The majority of the studies did not report on the duration of follow-up or oncological outcomes. Ten studies, including 296 patients, investigated the role of single-port robotic-assisted laparoscopy. The overall rate of intraoperative and postoperative complications was 1.0% and 7.1%, respectively. Two studies, including 38 patients, reported on the role of minilaparoscopy. None of these cases required conversion to laparotomy. Data on overall survival in the cohort of patients that underwent minilaparoscopy were not reported. We found only one publication reporting on the use of percutaneous laparoscopy. This prospective study included 30 patients. No complication was reported, and with a median follow-up time of 14 months (range 12-36) no recurrences were diagnosed.
CONCLUSIONS
Several ultra-minimally invasive surgical techniques have been developed and implemented in selected patients with endometrial cancer. The results of this review support the feasibility and perioperative safety of these approaches, while long-term outcomes are not adequately studied. However, further work is required in standardization of the techniques, in determining the learning curve of the operator and establishing their oncological safety.
Topics: Endometrial Neoplasms; Female; Gynecologic Surgical Procedures; Humans; Hysteroscopy; Laparoscopy; Minimally Invasive Surgical Procedures; Treatment Outcome
PubMed: 33205639
DOI: 10.23736/S0026-4806.20.07073-1 -
Cureus Sep 2023Higher mammographic breast density in premenopausal and postmenopausal women is related to a higher breast cancer risk. In this review, we analyze the correlation... (Review)
Review
Higher mammographic breast density in premenopausal and postmenopausal women is related to a higher breast cancer risk. In this review, we analyze the correlation between estrogen, progesterone, and mammographic density in postmenopausal women and clarify whether these findings are consistent across different types of mammographic breast density. We extracted data concerning mammographic density increases in the populations treated with estrogen-only hormone replacement therapy and those treated with estrogen and progestin hormone replacement therapy. Postmenopausal women treated with estrogen and progesterone regimens had a statistically significant lesser mammographic density increase than estrogen-only hormone replacement therapy regimens.
PubMed: 37868563
DOI: 10.7759/cureus.45597