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Frontiers in Neuroendocrinology Oct 2023Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females,... (Review)
Review
Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females, suggesting that drug addiction is a sexually differentiated disorder. The neurobiological bases of sex differences in SUD include sex-specific reward system activation, influenced by interactions between gonadal hormone level changes, dopaminergic reward circuits, and epigenetic modifications of key reward system genes. This systematic review, adhering to PICOS and PRISMA-P 2015 guidelines, highlights the sex-dependent roles of estrogens, progesterone, and testosterone in SUD. In particular, estradiol elevates and progesterone reduces dopaminergic activity in SUD females, whilst testosterone and progesterone augment SUD behavior in males. Finally, SUD is associated with a sex-specific increase in the rate of opioid and monoaminergic gene methylation. The study reveals the need for detailed research on gonadal hormone levels, dopaminergic or reward system activity, and epigenetic landscapes in both sexes for efficient SUD therapy development.
Topics: Female; Humans; Male; Dopamine; Epigenesis, Genetic; Gonadal Steroid Hormones; Meta-Analysis as Topic; Progesterone; Sex Characteristics; Substance-Related Disorders; Systematic Reviews as Topic; Testosterone
PubMed: 37543184
DOI: 10.1016/j.yfrne.2023.101085 -
The Cochrane Database of Systematic... Dec 2022Preterm birth (PTB), defined as birth prior to 37 weeks of gestation, occurs in ten percent of all pregnancies. PTB is responsible for more than half of neonatal and... (Review)
Review
BACKGROUND
Preterm birth (PTB), defined as birth prior to 37 weeks of gestation, occurs in ten percent of all pregnancies. PTB is responsible for more than half of neonatal and infant mortalities and morbidities. Because cervical insufficiency is a common cause of PTB, one possible preventive strategy involves insertion of a cervical pessary to support the cervix. Several published studies have compared the use of pessary with different management options and obtained questionable results. This highlights the need for an up-to-date systematic review of the evidence.
OBJECTIVES
To evaluate the benefits and harms of cervical pessary for preventing preterm birth in women with singleton pregnancies and risk factors for cervical insufficiency compared to no treatment, vaginal progesterone, cervical cerclage or bedrest.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform to 22 September 2021. We also searched the reference lists of included studies for additional records.
SELECTION CRITERIA
We included published and unpublished randomised controlled trials (RCTs) comparing cervical pessary with no treatment, vaginal progesterone, cervical cerclage or bedrest for preventing PTB. We excluded quasi-randomised trials. Our primary outcome was delivery before 34 weeks' gestation. Our secondary outcomes were 1. delivery before 37 weeks' gestation, 2. maternal mortality, 3. maternal infection or inflammation, 4. preterm prelabour rupture of membranes, 5. harm to woman from the intervention, 6. maternal medications, 7. discontinuation of the intervention, 8. maternal satisfaction, 9. neonatal/paediatric care unit admission, 10. fetal/infant mortality, 11. neonatal sepsis, 12. gestational age at birth, 13. harm to offspring from the intervention 14. birthweight, 15. early neurodevelopmental morbidity, 15. late neurodevelopmental morbidity, 16. gastrointestinal morbidity and 17. respiratory morbidity.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and risk of bias, evaluated trustworthiness based on criteria developed by the Cochrane Pregnancy and Childbirth Review Group, extracted data, checked for accuracy and assessed certainty of evidence using the GRADE approach.
MAIN RESULTS
We included eight RCTs (2983 participants). We included five RCTs (1830 women) in the comparison cervical pessary versus no treatment, three RCTs (1126 pregnant women) in the comparison cervical pessary versus vaginal progesterone, and one study (13 participants) in the comparison cervical pessary versus cervical cerclage. Overall, the certainty of evidence was low to moderate due to inconsistency (statistical heterogeneity), imprecision (few events and wide 95% confidence intervals (CIs) consistent with possible benefit and harm), and risk of performance and detection bias. Cervical pessary versus no treatment Cervical pessary compared with no treatment may reduce the risk of delivery before 34 weeks (risk ratio (RR) 0.72, 95% CI 0.33 to 1.55; 5 studies, 1830 women; low-certainty evidence) or before 37 weeks (RR 0.68, 95% CI 0.44 to 1.05; 5 studies, 1830 women; low-certainty evidence). However, these results should be viewed with caution because the 95% CIs cross the line of no effect. Cervical pessary compared with no treatment probably has little or no effect on the risk of maternal infection or inflammation (RR 1.04, 95% CI 0.87 to 1.26; 2 studies, 1032 women; moderate-certainty evidence). It is unclear if cervical pessary compared with no treatment has an effect on neonatal/paediatric care unit admission (RR 0.96, 95% CI 0.58 to 1.59; 3 studies, 1332 infants; low-certainty evidence) or fetal/neonatal mortality (RR 0.93, 95% CI 0.58 to 1.48; 5 studies, 1830 infants; low-certainty evidence) because the 95% CIs are compatible with a wide range of effects that encompass both appreciable benefit and harm. Cervical pessary versus vaginal progesterone Cervical pessary may reduce the risk of delivery before 34 weeks (RR 0.72, 95% CI 0.52 to 1.02; 3 studies, 1126 women; moderate-certainty evidence) or before 37 weeks (RR 0.89, 95% CI 0.73 to 1.09; 3 studies, 1126 women; moderate-certainty evidence), but we are uncertain of the results because the 95% CI crosses the line of no effect. The intervention probably has little or no effect on maternal infection or inflammation (RR 0.95, 95% CI 0.81 to 1.12; 2 studies, 265 women; moderate-certainty evidence). It is unclear if cervical pessary compared with vaginal progesterone has an effect on the risk of neonatal/paediatric care unit admission (RR 0.98, 95% CI 0.49 to 1.98; low-certainty evidence) or fetal/neonatal mortality (RR 1.97, 95% CI 0.50 to 7.70; 2 studies; 265 infants; low-certainty evidence) because the 95% CIs are compatible with a wide range of effects that encompass both appreciable benefit and harm. Cervical pessary versus cervical cerclage Only one very small study of 13 pregnant women contributed data to this comparison; the results were unclear.
AUTHORS' CONCLUSIONS
In women with a singleton pregnancy, cervical pessary compared with no treatment or vaginal progesterone may reduce the risk of delivery before 34 weeks or 37 weeks, although these results should be viewed with caution due to uncertainty around the effect estimates. There is insufficient evidence with regard to the effect of cervical pessary compared with cervical cerclage on PTB. Due to low certainty-evidence in many of the prespecified outcomes and non-reporting of several other outcomes of interest for this review, there is a need for further robust RCTs that use standardised terminology for maternal and offspring outcomes. Future trials should take place in a range of settings to improve generalisability of the evidence. Further research should concentrate on comparisons of cervical pessary versus cervical cerclage and bed rest. Investigation of different phenotypes of PTB may be relevant.
Topics: Female; Pregnancy; Humans; Pessaries; Cervix Uteri; Progesterone; Premature Birth; Cerclage, Cervical
PubMed: 36453699
DOI: 10.1002/14651858.CD014508 -
BMC Women's Health Jan 2024Menopause hormone therapy (MHT), as an effective method to alleviate the menopause-related symptoms of women, its benefits, risks, and potential influencing factors for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Menopause hormone therapy (MHT), as an effective method to alleviate the menopause-related symptoms of women, its benefits, risks, and potential influencing factors for the cardiovascular system of postmenopausal women are not very clear.
OBJECTIVES
To evaluate cardiovascular benefits and risks of MHT in postmenopausal women, and analyze the underlying factors that affect both.
SEARCH STRATEGY
The EMBASE, MEDLINE, and CENTRAL databases were searched from 1975 to July 2022.
SELECTION CRITERIA
Randomized Clinical Trials (RCTs) that met pre-specified inclusion criteria were included.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data independently. A meta-analysis of random effects was used to analyze data.
MAIN RESULTS
This systematic review identified 33 RCTs using MHT involving 44,639 postmenopausal women with a mean age of 60.3 (range 48 to 72 years). There was no significant difference between MHT and placebo (or no treatment) in all-cause death (RR = 0.96, 95%CI 0.85 to 1.09, I = 14%) and cardiovascular events (RR = 0.97, 95%CI 0.82 to 1.14, I = 38%) in the overall population of postmenopausal women. However, MHT would increase the risk of stroke (RR = 1.23, 95%CI 1.08 to 1.41,I = 0%) and venous thromboembolism (RR = 1.86, 95%CI 1.39 to 2.50, I = 24%). Compared with placebo, MHT could improve flow-mediated arterial dilation (FMD) (SMD = 1.46, 95%CI 0.86 to 2.07, I = 90%), but it did not improve nitroglycerin-mediated arterial dilation (NMD) (SMD = 0.27, 95%CI - 0.08 to 0.62, I = 76%). Compared with women started MHT more than 10 years after menopause, women started MHT within 10 years after menopause had lower frequency of all-cause death (P = 0.02) and cardiovascular events (P = 0.002), and more significant improvement in FMD (P = 0.0003). Compared to mono-estrogen therapy, the combination therapy of estrogen and progesterone would not alter the outcomes of endpoint event. (all-cause death P = 0.52, cardiovascular events P = 0.90, stroke P = 0.85, venous thromboembolism P = 0.33, FMD P = 0.46, NMD P = 0.27).
CONCLUSIONS
MHT improves flow-mediated arterial dilation (FMD) but fails to lower the risk of all-cause death and cardiovascular events, and increases the risk of stroke and venous thrombosis in postmenopausal women. Early acceptance of MHT not only reduces the risk of all-cause death and cardiovascular events but also further improves FMD, although the risk of stroke and venous thrombosis is not reduced. There is no difference in the outcome of cardiovascular system endpoints between mono-estrogen therapy and combination therapy of estrogen and progesterone.
Topics: Female; Humans; Middle Aged; Aged; Venous Thromboembolism; Postmenopause; Progesterone; Arteries; Stroke; Estrogens; Hormone Replacement Therapy; Venous Thrombosis; Risk Assessment
PubMed: 38263123
DOI: 10.1186/s12905-023-02788-0 -
Journal of Gynecologic Oncology Jul 2023To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.
METHODS
A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.
RESULTS
After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).
CONCLUSION
This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.
Topics: Pregnancy; Female; Humans; Male; Endometrial Hyperplasia; Progestins; Retrospective Studies; Neoplasm Recurrence, Local; Endometrial Neoplasms; Fertility Preservation; Treatment Outcome
PubMed: 36929578
DOI: 10.3802/jgo.2023.34.e49 -
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 -
The Cochrane Database of Systematic... Oct 2019Endometrial cancer is one of the most common gynaecological cancers in developed countries. Treatment of advanced endometrial cancer usually involves radiotherapy,... (Review)
Review
BACKGROUND
Endometrial cancer is one of the most common gynaecological cancers in developed countries. Treatment of advanced endometrial cancer usually involves radiotherapy, chemotherapy, endocrine therapy or a combination of these. However, survival outcomes are poor in advanced or metastatic disease. Better systemic treatment options are needed to improve survival and safety outcomes for these women. The PI3K/AKT/mTOR pathway is a frequently altered signalling pathway in endometrial cancer. Single-arm studies have reported some encouraging results of the PI3K/AKT/mTOR inhibition in advanced or recurrent endometrial cancer.
OBJECTIVES
To assess the efficacy and safety of PI3K/AKT/mTOR inhibitor-containing regimens in women with locally-advanced, metastatic or recurrent endometrial cancer.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase to 16 January 2019; and the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov in July 2018. We also reviewed reference lists from included studies and endometrial cancer guidelines.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing a regimen with a PI3K/AKT/mTOR inhibitor (either alone or in combination with other treatments, such as chemotherapy or hormonal therapy) versus a comparator regimen without a PI3K/AKT/mTOR inhibitor. There were no restrictions on which comparator(s) were included.
DATA COLLECTION AND ANALYSIS
We extracted data independently, and assessed risks of bias and the certainty of the evidence. The primary outcome measures were progression-free survival and toxicity (grade 3/4 where available). We derived hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) for dichotomous outcomes. Secondary outcomes included overall survival, objective tumour response rate, quality of life and treatment-related death. We used GRADEproGDT to assess the certainty of the evidence for the most important outcomes (by first-line and second/third-line therapy for progression-free survival and overall survival).
MAIN RESULTS
We included two RCTs involving 361 women. One study assessed the effects of the mTOR inhibitor temsirolimus, in combination with carboplatin/paclitaxel versus carboplatin/paclitaxel and bevacizumab in treatment-naïve women with advanced or recurrent endometrial cancer. The second study compared the mTOR inhibitor ridaforolimus alone versus progestin or investigator choice of chemotherapy in women who had received prior treatment for metastatic or recurrent endometrial cancer. We identified five ongoing studies on the effects of PI3K and AKT inhibitors, metformin and dual mTOR inhibitors.For first-line therapy, an mTOR inhibitor-containing regimen may worsen progression-free survival (HR 1.43, 95% CI 1.06 to 1.93; 1 study, 231 participants; low-certainty evidence), while for second/third-line therapy, an mTOR inhibitor probably improves progression-free survival compared to chemotherapy or endocrine therapy (HR 0.53, 95% CI 0.31 to 0.91; 1 study, 95 participants; moderate-certainty evidence). Data on toxicity were available from both studies: administering an mTOR inhibitor regimen may increase the risk of grade 3/4 mucositis (RR 10.42, 95% CI 1.34 to 80.74; 2 studies, 357 participants; low-certainty evidence), but may result in little to no difference in risk of anaemia or interstitial pneumonitis (low-certainty evidence for both toxicities). Overall, event rates were low. For first-line therapy, an mTOR inhibitor-containing regimen may result in little to no difference in overall survival compared to chemotherapy (HR 1.32, 95% CI 0.98 to 1.781 study, 231 participants; low-certainty evidence). The finding was similar for second/third-line therapy (HR 1.06, 95% CI 0.70 to 1.61; 1 study, 130 participants; low-certainty evidence). Administering mTOR inhibitor-containing regimens may result in little to no difference in tumour response compared to chemotherapy or hormonal therapy in first-line or second/third-line therapy (first line: RR 0.93, 95% CI 0.75 to 1.17; 1 study, 231 participants; second/third line: RR 0.22, 95% CI 0.01 to 4.40; 1 study, 61 participants; low-certainty evidence).Neither study collected or reported quality-of-life data.
AUTHORS' CONCLUSIONS
Two RCTs have been reported to date, with low certainty of evidence. In a recurrent disease setting, mTOR inhibitors may result in improved progression-free survival, but we found no clear benefit in overall survival or tumour response rate. We await the publication of at least five ongoing studies investigating the role of PI3K/AKT/mTOR inhibitors in advanced or recurrent endometrial cancer before any conclusions can be drawn on their use.
PubMed: 31588998
DOI: 10.1002/14651858.CD012160.pub2 -
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 -
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