Search

Background/Aims: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. Methods: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. Results: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93–1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42–1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. Conclusions: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk. [ABSTRACT FROM AUTHOR]

Positive (statistically significant) findings are easily produced in nutrition research when specific aspects of the research design and analysis are not accounted for. To address this issue, recently, a pledge was made to reform nutrition research and improve scientific trust on the science, encompass research transparency and achieve reproducibility. The aim of the present meta-epidemiological study was to evaluate the statistical significance status of research items published in three academic journals, all with a focus on clinical nutrition science and assessing certain methodological/transparency issues. All research items were published between the years 2015 and 2019. Study design, primary and secondary findings, sample size and age group, funding sources, positivist findings, the existence of a published research protocol and the adjustment of nutrients/dietary indexes to the energy intake (EI) of participants, were extracted for each study. Out of 2127 studies in total, those with positive findings consisted of the majority, in all three journals. Most studies had a published research protocol, however, this was mainly due to the randomized controlled trials and not to the evidence-synthesis studies. No differences were found in the distribution of positive findings according to the existence/inexistence of a published research protocol. In the pooled sample of studies, positive findings differed according to study design and more significant findings were reported by researchers failing to report any funding source. The majority of items published in the three journals (65.9%) failed to account for the EI of participants. The present results indicate that there is still room for the improvement of nutrition research in terms of design, analyses and reporting. [ABSTRACT FROM AUTHOR]

Patients on antithrombotics experiencing mild traumatic brain injury (mTBI) may benefit from a routine repeat CT scan to detect delayed intracranial hemorrhage (dICH). The primary outcome was the incidence of dICH on routine repeat CT scans of mTBI patients on antithrombotics within an intra-hospital observation period of up to 48 hours. The secondary outcomes were potential risk factors, readmissions, neurosurgical interventions, and mortality. A systematic review and a meta-analysis of single proportions were performed according to the PRISMA and PRESS guidelines. The risk of bias was assessed using Newcastle-Ottawa Scale. Eighteen studies with 4613 patients were included. The pooled incidence of dICH was 2% [95% CI 1-2%] with similar rates between different antithrombotic regimens, even in combination. Of the 67 patients with dICH reported (1.45%), eleven required surgery (0.24%), while six died (0.13%). Loss of consciousness was a risk factor of dICH (risk ratio 3.04 [95%CI 0.96; 9.58]). A total of 48 patients were reported for readmission without associated death or surgical intervention. The contribution of this routine repeat CT scan should be questioned due to the low incidence, the limited clinical significance, and the unsubstantiated clinical benefit of early or systematic detection of dICH. [ABSTRACT FROM AUTHOR]

Context: Whether preoperative vitamin D deficiency (VDD) contributes to postoperative hypoparathyroidism (hypoPT) risk is unknown.Objective: This work aimed to meta-analyze the best available evidence regarding the association between preoperative vitamin D status and hypoPT risk.Methods: A comprehensive literature search was conducted in PubMed, CENTRAL, and Scopus databases, up to October 31, 2020. Study selection included patients undergoing thyroidectomy with preoperative vitamin D status and postoperative hypoPT data. Two researchers independently extracted data from eligible studies. Data were expressed as risk ratio (RR) with 95% CI. The I2 index was employed for heterogeneity.Results: Thirty-nine studies were included in the quantitative analysis (61 915 cases with transient and 5712 with permanent hypoPT). Patients with VDD demonstrated a higher risk for transient hypoPT compared with those with preoperative vitamin D sufficiency (RR 1.92, 95% CI, 1.50-2.45, I2 = 85%). These results remained significant for patients with preoperative 25-hydroxyvitamin D concentrations less than or equal to 20 ng/mL (mild VDD; RR 1.46, 95% CI, 1.10-1.94, I2 = 88%) and less than or equal to 10 ng/mL (severe VDD; RR 1.98, 95% CI 1.42-2.76, I2 = 85%). The risk of permanent hypoPT was increased only in cases with severe VDD (RR 2.45, 95% CI, 1.30-4.63, I2 = 45%). No difference was evident in subgroup analysis according to study design or quality.Conclusion: Patients with preoperative VDD are at increased risk of transient hypoPT following thyroidectomy. The risk for permanent hypoPT is increased only for those with severe VDD. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is associated with an increased risk of fractures, mainly due to impaired bone architecture and microvascular complications. Whether DM is also associated with increased risk of sarcopenia is not yet known, with studies yielding inconclusive results. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between DM and sarcopenia risk. A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases. Data are expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. Only studies which had implemented at least two of the three criteria for sarcopenia diagnosis (low muscle mass, muscle strength and/or muscle performance), as defined by the international studying groups, were included. Fifteen studies fulfilled eligibility criteria, yielding a total of 1832 patients with type 2 DM (T2DM) and 1159 cases of sarcopenia. Patients with T2DM demonstrated a higher risk of sarcopenia compared with euglycemic subjects (OR 1.55, 95% CI 1.25–1.91, p < 0.001; I2 34.6%). This risk remained significant when analysis was restricted to studies matched for age and sex. Sarcopenia risk was independent of disease definition or study design. Notably, T2DM patients presented lower muscle performance and strength compared with euglycemic subjects, whereas no difference in muscle mass was observed between groups. Patients with T2DM have an increased risk of sarcopenia compared with euglycemic subjects. [ABSTRACT FROM AUTHOR]

Objective: Increased oxidative stress has been identified as a pathogenetic mechanism in female infertility. However, the effect of specific antioxidants, such as coenzyme Q10 (CoQ10), on the outcomes after assisted reproductive technologies (ART) has not been clarified. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of CoQ10 supplementation on clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR) compared with placebo or no-treatment in women with infertility undergoing ART. Methods: A comprehensive literature search was conducted in PubMed (MEDLINE), Cochrane, and Scopus, from inception to March 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. Results: Five randomized-controlled trials fulfilled eligibility criteria (449 infertile women; 215 in CoQ10 group and 234 in placebo/no treatment group). Oral supplementation of CoQ10 resulted in an increase of CPR when compared with placebo or no-treatment (28.8% vs. 14.1%, respectively; OR 2.44, 95% CI 1.30–4.59, p = 0.006; I2 32%). This effect remained significant when women with poor ovarian response and polycystic ovarian syndrome were analyzed separately. No difference between groups was observed regarding LBR (OR 1.67, 95% CI 0.66–4.25, p = 0.28; I2 34%) and MR (OR 0.61, 95% CI 0.13–2.81, p = 0.52; I2 0%). Conclusions: Oral supplementation of CoQ10 may increase CPR when compared with placebo or no-treatment, in women with infertility undergoing ART procedures, without an effect on LBR or MR. [ABSTRACT FROM AUTHOR]

Background: Women who achieve pregnancy by ART show an increased risk of obstetric and perinatal complications compared with those with spontaneous conception (SC).Objective and Rationale: The purpose of this systematic review and meta-analysis was to synthesize the best available evidence regarding the association between ART and gestational diabetes mellitus (GDM) in women with singleton pregnancies. The research question asked was whether the risk of GDM is higher in women achieving singleton pregnancy by ART compared with those achieving singleton pregnancy spontaneously.Search Methods: A literature search, in MEDLINE, Scopus and Cochrane databases, covering the period 1978-2019, was performed aiming to identify studies comparing the risk of GDM in singleton pregnancies after ART versus after SC. Both matched and unmatched studies were considered eligible. Meta-analysis of weighted data was performed using the random effects model. Results were reported as risk ratio (RR) with 95% CI. Heterogeneity was quantified with the I2 index.Outcomes: The study reports on 63 760 women who achieved a singleton pregnancy after ART (GDM was present in 4776) and 1 870 734 women who achieved a singleton pregnancy spontaneously (GDM in 158 526). Women with singleton pregnancy achieved by ART showed a higher risk of GDM compared with those with singleton pregnancy achieved spontaneously (RR 1.53, 95% CI 1.39-1.69; I2 78.6%, n = 37, 1 893 599 women). The direction or the magnitude of the effect observed did not change in subgroup analysis based on whether the study was matched (n = 17) or unmatched (n = 20) (matched: RR 1.42, 95% CI 1.17-1.72; I2 61.5%-unmatched: RR 1.58, 95% CI 1.40-1.78; I2 84.1%) or whether it was prospective (n = 12) or retrospective (n = 25) (prospective studies: RR 1.52, 95% CI 1.27-1.83, I2 62.2%-retrospective studies: RR 1.53, 95% CI 1.36-1.72, I2 82.5%). Regarding the method of fertilization, a higher risk of GDM after ART versus SC was observed after IVF (n = 7), but not after ICSI (n = 6), (IVF: RR 1.95, 95% CI 1.56-2.44, I2 43.1%-ICSI: RR 1.42, 95% CI 0.94-2.15, I2 73.5%). Moreover, regarding the type of embryo transfer (ET), a higher risk of GDM after ART versus SC was observed after fresh (n = 14) but not after frozen (n = 3) ET (fresh ET: RR 1.38, 95% CI 1.03-1.85, I2 75.4%-frozen ET: RR 0.46, 95% CI 0.10-2.19; I2 73.1%). A higher risk of GDM was observed after ART regardless of whether the eligible studies included patients with polycystic ovary syndrome (RR 1.49, 95% CI 1.33-1.66, I2 75.0%) or not (RR 4.12, 95% CI 2.63-6.45, I2 0%), or whether this information was unclear (RR 1.46, 95% CI 1.22-1.75, I2 77.7%).Wider Implications: The present systematic review and meta-analysis, by analysing 1 893 599 women, showed a higher risk of GDM in women achieving singleton pregnancy by ART compared with those achieving singleton pregnancy spontaneously. This finding highlights the importance of early detection of GDM in women treated by ART that could lead to timely and effective interventions, prior to ART as well as during early pregnancy. [ABSTRACT FROM AUTHOR]

The present systematic review and meta-analysis investigated the effects of hydralazine compared with other antihypertensive drugs in maternal, perinatal and neonatal outcomes of pregnant women with hypertensive disorders. Twenty studies with 1283 participants were included. Of them, 626 received hydralazine and 657 other antihypertensive treatments, such as labetalol, nifedipine, ketanserin, diazoxide, urapidil, isradipine and epoprostenol. Women receiving hydralazine had higher heart rate (WMD: 13.4, 95%CI: 0.1 to 26.8 beats/min), increased number of adverse effects (RR: 1.21, 95%CI: 1.01 to 1.45) and gave birth to neonates of lower birthweight (WMD: 13.4, 95%CI: 0.1 to 26.8 beats/min) compared with other antihypertensive treatments at the end of follow-up. When studies, which used antihypertensive agents that are no longer indicated for hypertension in pregnancy, were excluded in the sensitivity analyses, hydralazine found not to have a statistically significant difference compared with labetalol and nifedipine regarding the reduction of maternal blood pressure (WMD: 1.72, 95%CI: -1.47 to 4.9 mmHg for systolic, WMD: 0.26, 95%CI: -1.75 to 2.28 mmHg for diastolic), maternal heart rate (WMD: 13.56, 95%CI: -5.62 to 32.74 beats/min), low birthweight (WMD: -88.62, 95%CI: -243.24 to 66 beats/min) and adverse events (RR: 1.19, 95%CI: 0.99 to 1.43). Hydralazine seems not to be inferior compared to labetalol and nifedipine for safety and efficacy. [ABSTRACT FROM AUTHOR]

Objective: Graves' disease (GD) is an autoimmune thyroid disorder characterized by hyperthyroidism. The incidence of thyroid cancer in patients with GD varies from 0.15% to 15%. There is conflicting evidence on the role of thyroid nodules as a risk factor for thyroid cancer in patients with GD. Design: Three electronic databases (PubMed, Cochrane Library, Scopus) as well as grey literature sources were searched, from inception until 25 February 2019, for observational studies about the prevalence of thyroid cancer in patients with GD. Patients: Clinical and ultrasonographic examination was necessary preoperatively for all patients to be classified depending on the presence/absence of thyroid nodules. Measurements: Primary outcome was the incidence of thyroid cancer. The latter was determined after total or near‐total thyroidectomy by the histopathologic report. Statistical analysis was performed with revman 5.3 software. Results: The systematic review and meta‐analysis included 7 studies with 2582 patients overall. The prevalence of any thyroid cancer was 11.5%. The presence of at least one thyroid nodule in patients with GD was associated with higher risk for thyroid cancer (odds ratio [OR] 5.3, 95% confidence interval [CI] 2.4‐11.6, I2 83%). A subgroup analysis showed no difference in thyroid cancer risk in patients with GD according to the number of nodules (solitary versus multiple) (OR 1.4, 95% CI 0.9‐2.3, I2 0%). Conclusions: The presence of thyroid nodules is positively associated with the prevalence of thyroid cancer in surgically treated patients with GD. However, further prospective research is needed as the heterogeneity among the studies is high. [ABSTRACT FROM AUTHOR]

Objective/Design: Menopausal transition has been associated with a derangement of glucose metabolism. However, it is not known if early menopause (EM, defined as age at menopause <45 years) or premature ovarian insufficiency (POI, defined as age at menopause <40 years) are associated with increased risk of type 2 diabetes mellitus (T2DM). To systematically investigate and meta-analyze the best evidence regarding the association of age at menopause with the risk of T2DM. Methods: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to January 31, 2018. Data are expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. Results: Thirteen studies were included in the qualitative and quantita tive analysis (191 762 postmenopausal women, 21 664 cases with T2DM). Both women with EM and POI were at hig her risk of T2DM compared with those of age at menopause of 45-55 years (OR: 1.15, 95% CI: 1.04-1.26, P = 0.003; I2: 61%, P < 0.002 and OR: 1.50, 95% CI: 1.03-2.19, P = 0.033; I2: 75.2%, P < 0.003), respectively). Similar associations emerged when women with EM and POI were compared with those of age at menopause >45 years (OR: 1.12, 95% CI: 1.01-1.20, P < 0.02; I2: 78%, P < 0.001 and OR: 1.53, 95% CI: 1.03-2.27, P = 0.035; I2: 78%, P < 0.001), respectively). Conclusions: Both EM and POI are associated with increased risk of T2DM. [ABSTRACT FROM AUTHOR]

• There is an epidemiological association between multiple sclerosis (MS) and chronic periodontitis (CP). • Inflammatory mechanisms play an important role in the association between CP and MS. • Treatment of CP may help prevent and improve MS outcome. Chronic periodontitis (CP) is a multifactorial, chronic inflammatory disease of microbial etiology that manifests as a result of the dysfunction of the immune mechanism, culminating in the destruction of the alveolar bone of the jaws. Multiple sclerosis (MS) is an autoimmune disorder that affects the central nervous system (CNS), leads to demyelination and degeneration of nerve axons and often causes severe physical and/or cognitive impairment. As CP and MS involve inflammatory mechanisms and immune dysfunction, researchers have attempted to study the association between them. To systematically review the literature on the epidemiological association between CP and MS in adults. PRISMA 2020 statement was used in the study protocol. The design was done according to the Cochrane methodology. A comprehensive literature search was performed in PubMed, Scopus and Cochrane databases; a manual search and evaluation of the gray literature was also performed. The meta-analysis was performed by Review Manager (RevMan) 5.4. Odds ratio (OR) with 95% confidence interval (CI) was defined as the effect size of the outcome. Heterogeneity was assessed by Chi-square and I2. The articles evaluated were written in English, without a time limit, concern observational studies (patient-controls) and report the diagnostic criteria of the diseases. Duplicate entries were excluded. To evaluate the reliability of the results of each study, Newcastle-Ottawa Scale (NOS) and GRADE tools were used. Two independent reviewers did all evaluations with a resolution of discrepancies by a third. Meta-analysis included three observation studies examined 3376 people. MS patients are significantly more likely to be diagnosed with CP than healthy controls (OR 1.93, 95% CI 1.54–2.42, p <0.0001). A high prevalence of CP was found among MS patients compared with healthy controls. Healthcare professionals should be aware of the association between these pathological entities to provide patients with high-quality care through an effective and holistic diagnostic and therapeutic approach. [ABSTRACT FROM AUTHOR]

BACKGROUND The relation between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD) remains unclear. In an attempt to provide high-quality evidence on the relation between PCOS and CVD, relevant literature for CVD risk markers [C-reactive protein (CRP), homocysteine (Hcy), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), lipoprotein (a) [Lp(a)], advanced glycation end-products (AGEs), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1) and fibrinogen] in women with PCOS was reviewed and analyzed. METHODS A systematic search was conducted electronically using specific eligibility criteria. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated and combined appropriately. To ensure synthesis of the best available evidence, sensitivity analyses were performed. RESULTS A total of 130 data sets were included in 11 different outcomes, involving 7174 and 5076 CVD markers in women with PCOS and controls, respectively. Women with PCOS demonstrated significantly elevated CRP [WMD (95% CI) 0.99 (0.77–1.21)], Hcy [2.25 (1.46–3.03)], PAI-1 antigen [16.96 (7.25–26.28)], PAI-1 activity [0.71 (0.18–1.23)], VEGF [1.72 (0.96–2.48)], ADMA [0.19 (0.08–0.3)], AGEs [3.91 (2.36–5.45)] and Lp(a) [0.81 (0.58–1.04)] concentrations compared with controls, yet with significant between-study heterogeneity. Borderline significance (not robust in the sensitivity analyses) was detected for TNF-α [0.75 (0.07–1.44)], ET-1 [1.06 (0.52–1.59)] and fibrinogen [0.20 (0.01–0.39)], whereas no difference was detected for IL-6 [0.71 (−0.16 to 1.59)]. CONCLUSIONS Women with PCOS have increased serum concentrations of CVD risk markers compared with controls. Whether this apparent risk is translated into increased incidence of CVD in later life remains to be elucidated. [ABSTRACT FROM PUBLISHER]

Abstract: Hypoadiponectinemia might represent a risk factor for nonalcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to evaluate the serum total adiponectin levels in patients with simple nonalcoholic fatty liver (NAFL), those with nonalcoholic steatohepatitis (NASH), and controls. Data were extracted from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials electronic databases (up to December 2009). The main outcome was the weighted mean differences (WMDs) in adiponectin between comparison groups. Twenty-eight studies were included in the systematic review. A meta-analysis of 27 studies that reported data on 2243 subjects (698 controls and 1545 patients with NAFLD) was performed. Controls had higher serum adiponectin compared with NAFL patients (12 studies, random-effects WMD [95% confidence interval {CI}] = 3.00 [1.57-4.43], I 2 = 80.4%) or NASH patients (19 studies, random-effects WMD [95% CI] = 4.75 [3.71-5.78], I 2 = 84.1%). The NASH patients demonstrated lower adiponectin compared with NAFL patients (19 studies, random-effects WMD [95% CI] = 1.81 [1.09-2.53], I 2 = 71.7%). By performing a meta-regression analysis, body mass index, age, sex, and type 2 diabetes mellitus failed to account for heterogeneity. However, the performance of liver biopsy on controls had significant effect on the outcome and accounted for 76.7%, 85.5%, and 22.8% of the between-study variance for comparisons between controls vs NAFLD, NAFL, and NASH patients, respectively. Based on liver histology, serum adiponectin levels are similar in NAFL patients and controls, but hypoadiponectinemia may play an important pathophysiological role in the progression from NAFL to NASH. [Copyright &y& Elsevier]

INTRODUCTION A non-invasive test, which could predict the presence of sperm during a testicular sperm extraction (TESE) procedure in men with non-obstructive azoospermia (NOA), would be of profound clinical importance. Inhibin B (Inh-B) and anti-Müllerian hormone (AMH) have been proposed as direct markers of Sertoli cell function and indirect markers of spermatogenesis. METHODS A search was conducted in the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through June 2009. Thirty-six different studies reported data on the predictive value of one or more index markers (serum Inh-B: 32 studies, seminal Inh-B: 5 studies, serum AMH: 2 studies, seminal AMH: 4 studies) and were included in the systematic review. Nine studies, which had serum Inh-B as index marker, met the predefined criteria and were included in the meta-analysis. RESULTS Serum Inh-B demonstrated a sensitivity of 0.65 (95% confidence interval [CI]: 0.56–0.74) and a specificity of 0.83 (CI: 0.64–0.93) for the prediction of the presence of sperm in TESE. When the pre-test probability of 41% was incorporated in a Fagan's nomogram, resulted in a positive post-test probability of 73% and a negative post-test probability of 23% for the presence of sperm in TESE. CONCLUSIONS Serum Inh-B cannot serve as a stand-alone marker of persistent spermatogenesis in men with NOA. Although limited, evidence on serum AMH and serum/seminal AMH do not support their diagnostic value in men with NOA. [ABSTRACT FROM PUBLISHER]

Objective: To evaluate the risk of gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS). Design: Systematic review and meta-analysis of observational studies. Setting: Tertiary Department of Reproductive Endocrinology. Patient(s): Five thousand two hundred ninety-three pregnant women (721 with PCOS and 4,572 controls without PCOS). Intervention(s): Literature search in the electronic databases MEDLINE, EMBASE, and CENTRAL, study of the references of all relevant trials or reviews, and manual search of the abstracts from the major meetings in the field of human reproduction. Main Outcome Measure(s): Gestational diabetes mellitus odds ratio. Result(s): Women with PCOS demonstrated a significantly higher risk for the development of GDM as compared with women without PCOS (odds ratio 2.89, 95% confidence interval [CI] 1.68–4.98), yet with significant statistical heterogeneity (I2 = 59.3%), durable to sensitivity analysis. In the subgroup of cohort studies, this finding remained robust (7.11, 95% CI 2.95–17.12), whereas in the subgroup of case-control studies, it did not (0.89, 95% CI 0.38–2.06). Metaregression modeling revealed a linear dependence of the outcome on study type and baseline risk (post hoc). Conclusion(s): Significant heterogeneity among studies and dependence of the outcome on study type make the higher risk of GDM in women with PCOS a questionable finding. The conduction of properly designed studies should precede any recommendation to pregnant women with PCOS in regard to the risk of GDM. [Copyright &y& Elsevier]

Aims: Several interventions have been implemented to prevent the development of gestational diabetes mellitus (GDM) in obese pregnant women, including physical exercise programs, and administration of metformin, vitamin D and probiotics. The aim of this network meta-analysis was to compare the efficiency of these interventions and identify the optimal.Materials: A network meta-analysis of randomized trials was performed comparing the different interventions for the development of GDM in overweight or obese women, either to each other or placebo/no intervention. A search was conducted in four electronic databases and grey literature sources. The primary outcome was the development of GDM; secondary outcomes were other complications of pregnancy.Results: The meta-analysis included 23 studies (4237 participants). None of the interventions was superior compared with placebo/no intervention for the prevention of GDM. Metformin and physical exercise were superior to placebo/no intervention for gestational weight gain (MD -1.21, 95% CI -2.14 to -0.28 and MD -0.96, 95% CI -1.69 to -0.22, respectively). Metformin was superior to placebo/no intervention for caesarean sections and admission to NICU.Conclusions: Interventions aiming to prevent the development of GDM in overweight/obese women are not effective, when applied during pregnancy. [ABSTRACT FROM AUTHOR]

Aim: Sex hormones have been suggested to have neuroprotective effects in the natural history of multiple sclerosis (MS), particularly in animal studies. The aim of the present review was to retrieve and systematically synthesize the evidence on the effect of menopause and hormonal replacement treatment (HRT) on the course of MS.Methods: A systematic literature search was conducted in the databases MEDLINE (accessed through PubMed), Scopus, clinicaltrials.gov and Cochrane Controlled Register of Trials (CENTRAL). Eligible studies were all those that included women with MS and reported on at least one of the following: a) disability and MS relapse rate before and after menopause, b) serum sex hormone concentrations, c) sexual function, d) age at menopause onset. Effects of HRT on MS clinical outcomes were also assessed.Results: Of the 4,102 retrieved studies, 28 were included in the systematic review. Of these, one reported the age at menopause for both controls and women with MS and found no difference between the two groups. There was no difference in the rates of relapse before and after menopause (risk ratio 1.21, 95 % confidence interval 0.91-1.61, p = 0.218). Two intervention studies reported beneficial effects of estrogen therapy on women with MS; however, the majority of women were premenopausal. Three studies addressed the issue of sexual dysfunction in women with MS, but information on hormonal parameters was limited.Conclusions: The age at menopause is not associated with the presence of MS. The evidence on a potential causal effect of estrogen depletion on disability is inconclusive; still, relapse rate seems not be associated with menopause. The effect of HRT on the natural course of the disease remains to be defined. [ABSTRACT FROM AUTHOR]

Objective: To clarify the effect of programmed exercise (PE), performed for at least six weeks, on perceived stress (PS) in middle aged and old women.Methods: A structured search was carried out in PubMed, Embase, Cochrane Library, Scielo, Web of Science and Scopus, from database inception through January 10, 2018, without language restriction. The US, UK, and Australian clinical trials databases were also searched. The search included a combination of the terms "programmed exercise", "perceived stress", "menopausal women" and "randomized controlled trial" (RCTs). PE was classified according to duration as "mid-term exercise intervention" (MTEI; mean duration 6 months), and "long-term exercise intervention" (LTEI; mean duration 12 months). Mean ± standard deviations of changes in PS scores, as assessed with different questionnaires, were calculated as standardized mean differences (SMDs) and used as effect size for meta-analysis. SMDs of PS after intervention were pooled using a random-effects model. Study quality and bias risk were assessed with the Cochrane tool.Results: Five RCTs that studied midlife and older women (mean age 47.0 ± 1.7 years minimum to 71.8 ± 5.6 maximum) were included in the meta-analysis. There was no significant effect of PE on PS score (SMD: -0.16; 95% CI: -0.43 to 0.11). In subgroup analyses, there was no significant effect of PE on PS with mid-term interventions (SMD: - 0.17; 95% CI: -0.59 to 0.25) nor with long-term interventions (SMD: -0.02; 95% CI: -0.42 to 0.38) as compared with controls.Conclusion: PE of low to moderate intensity does not improve PS in midlife and older women. [ABSTRACT FROM AUTHOR]

Objective: Transition to menopause has been associated with an increased risk of cardiovascular disease (CVD), attributed mainly to atherogenic dyslipidemia. Whether lipoprotein (a) [Lp(a)], an independent cardiovascular risk factor, also contributes to menopause-associated CVD has not yet been clarified. The aim of this study was to systematically investigate and meta-analyze the best available evidence regarding the effect of menopause on Lp(a) concentrations.Methods: A comprehensive search was conducted in PubMed and Scopus databases up to March 8th, 2022. Data were expressed as weighted mean difference (WMD) with 95 % confidence intervals (CI). The I2 index was employed to assess heterogeneity.Results: Seventeen studies were included in the qualitative and 15 in the quantitative analysis, yielding 4686 premenopausal and 8274 postmenopausal women. Lp(a) concentrations were lower in premenopausal than in postmenopausal women [WMD -3.77 (95 % CI -5.37, -2.18) mg/dl, p < 0.001; I2 99%, p < 0.001]. This difference was maintained when the analysis was restrained to good-quality studies (n = 9). Four studies included pre- and postmenopausal women, matched for age, and these found no difference in Lp(a) concentrations between groups [WMD -1.22 (95 % CI -3.15, 0.72) mg/dl, p < 0.001; I2 99%, p < 0.001]. Three studies provided data for Lp(a) in women before and after bilateral oophorectomy, and these found no difference between them [WMD -3.38 (95 % CI -7.29, 0.54) mg/dl, p = 0.09; I2 0%, p < 0.44].Conclusions: Transition to menopause may increase Lp(a) concentrations, although the effect of aging cannot be excluded by current data. [ABSTRACT FROM AUTHOR]

Aim: Radioactive iodine (RAI) is frequently used as adjuvant therapy in patients with differentiated thyroid cancer (DTC). However, its effect on ovarian reserve has not been fully elucidated, with studies yielding inconsistent results. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of RAI on ovarian reserve in premenopausal women with DTC.Methods: A comprehensive literature search was conducted in PubMed, Cochrane and Scopus, through to December 6th, 2020. Data were expressed as weighted mean difference (WMD) with a 95% confidence interval (CI). The I2 index was used to assess heterogeneity.Results: Four prospective studies were included in the qualitative and quantitative analysis. Anti-Müllerian hormone (AMH) concentrations decreased at three (WMD -1.66 ng/ml, 95% CI -2.42 to -0.91, p<0.0001; I2 0%), six (WMD -1.58, 95% CI -2.63 to -0.52, p=0.003; I2 54.7%) and 12 months (WMD -1.62 ng/ml, 95% CI -2.02 to -1.22, p<0.0001; I2 15.5%) following a single RAI dose compared with baseline (three studies; n=104). With respect to follicle-stimulating hormone (FSH) concentrations, no difference was observed at six (WMD +3.29 IU/l, 95% CI -1.12 to 7.70, p=0.14; I2 96.8%) and 12 months (WMD +0.13 IU/l, 95% CI -1.06 to 1.32, p=0.83; I2 55.2%) post-RAI compared with baseline (two studies; n=83). No data were available for antral follicle count.Conclusions: AMH concentrations are decreased at three months and remain low at 6 and 12 months following RAI treatment in women with DTC. No difference in FSH concentrations post-RAI is observed. [ABSTRACT FROM AUTHOR]

Purpose: The exact effect of vitamin D supplementation, either as monotherapy or in combination with protein, on musculoskeletal health in patients with sarcopenia is currently unknown. This study aimed to determine the effect of vitamin D alone or with protein supplementation on muscle strength, mass, and performance in this population.Methods: A comprehensive search was conducted in Medline, Cochrane Central and Scopus databases, up to March 31st, 2020. Data were expressed as standardized mean difference (SMD) with 95 % confidence intervals (CI). I2 index was employed for heterogeneity.Results: The initial search identified 1164 studies, eight of which met the eligibility criteria for qualitative and quantitative analysis, yielding a total of 776 patients. Vitamin D (100-1600 IU/day) plus protein (10-44 g/day) supplementation exhibited a beneficial effect on muscle strength, as demonstrated by an improvement in handgrip strength (SMD 0.38 ± 0.07, 95 % CI 0.18-0.47, p = 0.04; I2 76.2 %) and a decrease in the sit-to-stand time (SMD 0.25 ± 0.09, 95 % CI 0.06-0.43, p = 0.007; I2 0%) compared with placebo. However, the effect on muscle mass, assessed by skeletal muscle index, was marginally non-significant (SMD 0.25 ± 0.13, 95 % CI -0.006-0.51, p = 0.05; I2 0%). No effect on appendicular skeletal muscle mass or muscle performance (assessed by walking speed) was observed with vitamin D plus protein.Conclusions: Vitamin D supplementation, combined with protein, improves muscle strength in patients with sarcopenia, but has no effect on muscle mass or performance. [ABSTRACT FROM AUTHOR]

Objective: Menopausal transition has been associated with an increased risk of cardiovascular disease (CVD), mainly attributed to atherogenic dyslipidaemia, central obesity and insulin resistance. Whether arterial hypertension (AH) also contributes to menopause-associated CVD is currently unknown. The aim of this study was to systematically investigate and meta-analyze the best available evidence regarding the association between early menopause (EM) and AH risk.Methods: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases, up to January 20th, 2020. Data were expressed as odds ratio (OR) with 95 % confidence intervals (CI). The I2 index was employed for heterogeneity.Results: Ten studies were included in the quantitative analysis (273,994 postmenopausal women, 76853 cases with AH). Women with EM (age at menopause <45 years) were at higher AH risk compared with those of normal age at menopause (>45 years) (OR 1.10, 95 % CI 1.01-1.19, p = 0.03; I2 79 %). The direction or the magnitude of this association remained significant when the analysis was restricted to studies including groups matched for potential confounders, such as age, BMI, smoking or the use of menopausal hormone therapy or oral contraceptives.Conclusions: Women with EM have an increased risk for AH compared with those of normal age at menopause. [ABSTRACT FROM AUTHOR]

Hyperemesis gravidarum (HG) is the main cause of hospitalization during the first trimester of pregnancy. Although it has been associated with serious complications, little is known about its predictive factors. The aim of this systematic review was to search for and critically appraise the studies that investigate the predictive factors for HG. Search strategy included PubMed, CENTRAL and EMBASE databases (till December 2017). All studies examining risk factors for HG were included. Screening of available studies was carried out by two reviewers, as well as the quality assessment of the included studies, based on the Newcastle-Ottawa Scale for observational studies. The search located 308 articles, of which 14 observational studies (four low-, eight medium- and two high-quality), involving 1400 women who met the eligibility criteria. In four studies, there was no association between Helicobacter (H.) Pylori infection and HG, in contrast to two studies which demonstrated such an association. Pre-pregnancy body mass index (BMI), adipose tissue, maternal age, leptin, ghrelin, beta-chorionic gonadotropin (β-hCG), total (T 4) and free thyroxine (fT 4) correlated with HG in various studies, and could be considered as predictive markers. Regarding the high-quality evidence, a cohort study associated leptin and nephatin-1 with HG, whereas a cross-sectional study found no association between H. pylori infection and HG. More studies of high quality and adequate sample size have to be carried out to identify the predictive factors for HG. [ABSTRACT FROM AUTHOR]

Background: Phytoestrogens constitute an alternative, non-pharmacologic approach for the management of menopausal symptoms. However, few studies have focused on their safety, specifically in relation to endometrial thickness and breast density.Aim: To systematically search for and quantitatively synthesize the evidence regarding the effect of phytoestrogens on endometrial thickness and breast density in perimenopausal and postmenopausal women.Methods: Randomized controlled trials (RCTs) examining the effect of phytoestrogens compared with placebo or menopausal hormone therapy (MHT) on endometrial thickness and/or breast density in perimenopausal or postmenopausal women were searched for in the MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources until October 31, 2018. Main outcomes were the change from baseline in endometrial thickness and breast density. Statistical analysis was performed with RevMan 5.3, using R language and Open Meta-Analyst software.Results: The meta-analysis for endometrial thickness included 30 RCTs (with a total of 3497 women), and that for breast density four RCTs (with a total of 674 women). Phytoestrogens did not affect endometrial thickness compared with placebo [weighted mean difference (WMD) -0.04 mm, 95% confidence interval (CI) -0.18 to 0.11, I2 66%] or MHT (WMD -1.40 mm, 95% CI -2.98 to 0.18, I2 84%). In addition, phytoestrogens did not affect breast density compared with placebo [standardized mean difference (SMD) -0.76, 95% CI -1.54 to 0.2, I2 95%).Conclusion: Phytoestrogens have no effect on endometrial thickness or breast density, when administered at various doses and for various durations, in perimenopausal and postmenopausal women. However, the high heterogeneity of the studies makes it necessary to conduct RCTs with less risk of systematic error. [ABSTRACT FROM AUTHOR]

Objective: Data on the effect of hormone replacement therapy (HRT) and tibolone on lipoprotein (a) [Lp(a)], an independent risk factor for cardiovascular disease, are heterogeneous and conflicting. Studies of the effect of HRT and tibolone on Lp(a) concentrations in post-menopausal women are reviewed in this meta-analysis.Design and Methods: MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to February 10, 2017). Two researchers identified randomized controlled studies and extracted data. Potential controversies were resolved by a third reviewer.Results: In 24 eligible studies, HRT caused a significant reduction in Lp(a) concentrations compared with placebo or no treatment [mean relative difference: -20.35%, 95% Confidence Interval (CI): -25.33% to -15.37%, p<0.0001], with significant heterogeneity between studies (I2=98.5%), but without evidence of publication bias. No significant effect was found for tibolone (n=7) (mean relative difference: -23.84%, 95% CI: -63.43% to 15.74%, p=0.238) (I2=98.7%, but without publication bias). Oral estrogen caused a greater reduction in Lp(a) concentrations than transdermal estrogen (n=10) (mean relative difference: 37.66%, 95% CI: 16.84% to 58.48%, p<0.0001), with significant heterogeneity between studies (I2=99%), but no evidence of publication bias. No difference was observed when continuous was compared with cyclical HRT, conventional with low-dose estrogen, and estrogen monotherapy with estrogen combined with progestogen. No difference was observed between HRT and tibolone regarding their effect on Lp(a).Conclusions: HRT significantly decreases Lp(a) concentrations, with oral being more effective than transdermal estradiol. The type of HRT, dose of estrogen and addition of progestogen do not seem to modify the Lp(a)-lowering effect of HRT. [ABSTRACT FROM AUTHOR]

Aims: To compare the safety and efficacy of insulin detemir versus neutral protamine Hagedorn (NPH) in pregnant women with diabetes.Methods: MEDLINE, CENTRAL, Google Scholar databases, and ClinicalTrials.gov registry were searched from inception to December 2021 to identify randomized controlled trials (RCTs) concerning adult women with singleton pregnancies, gestational or pregestational diabetes, and the need for insulin therapy. A systematic review and a meta-analysis (weighted data, random-effects model) were performed. Continuous outcomes were expressed as mean difference (MD) with 95% confidence interval (CI) (inverse variance method); dichotomous outcomes were expressed as risk ratio (RR) with 95% CI (Mantel-Haenszel method). Heterogeneity was quantified using the I2 index.Results: Five RCTs involving 1450 participants met the inclusion criteria. Outcomes that showed significant results in favor of insulin detemir over NPH were maternal hypoglycemic events (RR 0.64, 95% CI 0.48-0.86, p = 0.003; I2 = 0%) and gestational age at delivery (MD 0.48, 95% CI 0.16-0.81, p = 0.003; I2 = 0%).Conclusions: Insulin detemir was associated with less maternal hypoglycemic events and decreased risk for prematurity compared with NPH insulin. More research should be conducted to reach a safe conclusion about the optimal insulin regimen for women with diabetes in pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Various nonhormonal agents have been used for the treatment of hot flashes in women with natural or tamoxifen-induced menopause. Some studies have reported that gabapentin appears to be an effective and well-tolerated treatment modality. Objective: To investigate the efficacy and tolerability of gabapentin for the treatment of menopausal hot flashes, we performed a systematic review of all trials reporting on the efficacy and tolerability of gabapentin in women with hot flashes and a meta-analysis of the randomized controlled trials (RCTs) conducted in this patient population. Methods: For the systematic review, a literature search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for articles published in English from inception of the databases through November 2008. The reference sections of retrieved articles were searched, and a manual search of key journals and abstracts from major meetings in clinical pharmacology was conducted. To be included in the meta-analysis, RCTs had to compare gabapentin with placebo in the treatment of hot flashes in women with natural or tamoxifen-induced menopause, regardless of the sample size, dosage used, duration of treatment, or frequency of the episodes. Uncontrolled and openlabel trials were reviewed but excluded from the meta-analysis. The percent reduction in hot flash frequency (relative to baseline) and the composite score (summation of the number of hot flashes in each severity category multiplied by the severity score) were used as primary outcome measures. Dropout rates and the incidences of frequently reported adverse events (eg, dizziness/unsteadiness, fatigue/somnolence) were also investigated. Results: The systematic review included 7 trials conducted in 901 patients between 2002 and 2008. Study sizes ranged from 22 to 420 patients, total daily doses of gabapentin ranged from 900 to 2400 mg, and titration periods lasted 3 to 12 days. All of the trials were conducted in North America (6 in the United States and 1 in Canada); 4 of the trials enrolled subjects with a history of breast cancer, whereas the remaining 3 trials only enrolled postmenopausal women. Four RCTs were included in the meta-analysis. Data were expressed as weighted mean difference (WMD) or relative risk (RR), with the associated 95% CI. Women assigned to gabapentin reported a significantly greater percent reduction in both the frequency of hot flashes (WMD = 23.72 [95% CI, 16.46–30.97]; P < 0.001) and the composite score (WMD = 27.26 [95% CI, 21.24–33.29]; P < 0.001), with significant between-study heterogeneity (I 2 = 97.8% and 95.6%, respectively). Dropouts due to adverse events were more frequent in women randomized to gabapentin than in controls (RR = 2.09 [95% CI, 1.13–3.85]; P = 0.02; I 2 = 0%). The risk of symptom clustering also was significantly higher in the treatment group than in the controls (dizziness/unsteadiness: RR = 6.94 [95% CI, 3.19–15.13]; P < 0.001; I 2 = 63.1%; and fatigue/somnolence: RR = 4.78 [95% CI, 2.23–10.25]; P < 0.001; I 2 = 0%). Conclusions: Comparisons of gabapentin and placebo revealed reductions of 20% to 30% in the frequency and severity of hot flashes with gabapentin, although data across the studies were too heterogeneous to provide a reliable summary effect. Clusterings of dizziness/unsteadiness and fatigue/somnolence were the most frequently reported adverse events associated with gabapentin and resulted in a higher dropout rate due to adverse events in the gabapentin-treated patients than in the controls. More studies are needed to consolidate the outcomes and elucidate useful details regarding this treatment. [Copyright &y& Elsevier]

Objective: To reappraise the currently available evidence, providing the answer to the following question: does intravenous albumin administration reduce the risk of severe ovarian hyperstimulation syndrome (OHSS) occurrence following ovarian stimulation with gonadotrophins and GnRH analogues for IVF in high-risk patients? Design: Systematic review and metaanalysis. Setting: University-based hospital. Intervention(s): Intravenous albumin administration in high-risk patients for prevention of severe OHSS occurrence. Main Outcome Measure(s): Severe OHSS occurrence. Result(s): Eight eligible randomized controlled trials were identified (n = 1,199 patients) that offered data for statistical pooling. No statistically significant difference in the occurrence of severe OHSS in patients who received intravenous albumin (n = 595) and those who did not (n = 604; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.52–1.22) was detected. Moreover, no statistically significant differences were present regarding the probability of pregnancy (OR, 0.83; 95% CI, 0.64–1.07) and first trimester pregnancy loss (OR, 1.44; 95% CI, 0.73–2.85) between patients who received intravenous albumin and those who did not. Conclusion(s): Based on the currently best available evidence, intravenous albumin administration in high-risk patients does not appear to reduce the occurrence of severe OHSS. This finding should be considered when implementing strategies for severe OHSS prevention. [Copyright &y& Elsevier]