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The Lancet. Psychiatry Sep 2023Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines required updated evidence synthesis to improve their current recommendations. In order to inform evidence-based prescribing, we investigated the comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression.
METHODS
We conducted a systematic review and network meta-analysis. We searched for randomised controlled trials comparing pharmacological interventions with each other or placebo in adults with acute bipolar depression (type I, type II, or not otherwise specified), excluding those with substance misuse, unipolar depression, or schizophrenia, in MEDLINE, Embase, PsycINFO, Google Scholar, Cochrane Library, Web of Knowledge, CINAHL, and LILACS from database inception up to April 13, 2023. Criteria for eligibility were a duration of 2-16 weeks with masked outcome assessments, and we included combination, add-on design, and monotherapy studies. The co-primary outcomes were depressive symptoms, examined with standardised mean differences (SMDs), and manic switch, examined with odds ratios (ORs). We also investigated dropouts due to any reason, inefficacy, adverse events, and important side-effects as secondary outcomes. The confidence in the evidence was evaluated using Confidence-In-Network-Meta-Analysis (CINeMA). The study was registered with PROSPERO, CRD42020171726.
RESULTS
We analysed data from 101 randomised controlled trials covering 20 081 participants, 8063 men (41·7%) and 11 263 women (58·3%; sex not available in four studies), mean age 41·0 years (range of means 28·7-53·6 years), and 68 medications and placebo. Ethnicity data were not available. With moderate confidence in the evidence, olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were more efficacious than placebo in reducing depressive symptoms, with SMDs ranging from 0·41 (95% CI 0·19-0·64) for olanzapine plus fluoxetine to 0·16 (0·03-0·29) for lamotrigine. Several other drugs might also be efficacious, but the confidence in the evidence was very low to low. Antidepressants as a class seem to be efficacious, but had a higher risk for manic switch compared to antipsychotics. Medications differed in their side-effect profiles.
INTERPRETATION
This is, to our knowledge, the largest network meta-analysis of pharmacotherapy for bipolar depression to date. Olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were found to be more efficacious than placebo in adults with acute bipolar depression, with good confidence in the evidence, and to differ in their side-effect profiles. These findings can inform evidence-based care and the development of treatment guidelines internationally.
FUNDING
None.
Topics: Male; Adult; Female; Humans; Middle Aged; Bipolar Disorder; Depression; Fluoxetine; Lamotrigine; Olanzapine; Lurasidone Hydrochloride; Quetiapine Fumarate; Network Meta-Analysis; Drug-Related Side Effects and Adverse Reactions
PubMed: 37595997
DOI: 10.1016/S2215-0366(23)00199-2 -
Psychiatry Research May 2023Transidentity and autism frequently co-occur. Previous reviews have focused mainly on frequencies. Here, we conducted a systematic review to condense all the studies and... (Review)
Review
Transidentity and autism frequently co-occur. Previous reviews have focused mainly on frequencies. Here, we conducted a systematic review to condense all the studies and themes on this co-occurrence and to offer a global view. We followed the PRISMA method and selected 77 articles (including 59 clinical studies) in April 2022. We found 5 main themes (sex ratio, theories, sexual orientation, clinical and social consequences, and care implications) in addition to frequencies. Many theories have been proposed to explain the co-occurrence. One posits that social difficulties related to autism would lead to less identification with gender norms and less pressure to conform to these norms, allowing for greater gender diversity in people with autism. Given their difficulties with social interactions and communication, the announcement of one's transidentity to one's social group is often discredited, increasing the risk of suffering and delayed care. Many reports reaffirm the importance of providing specialised care for transgender people with autism. Autism is not a contraindication for gender-affirming treatment. However, some cognitive specificities can affect the planning of care, and transgender people with autism are at high risk of discrimination and harassment. We conclude that there is a need to raise awareness about gender and autism.
Topics: Humans; Male; Female; Autism Spectrum Disorder; Gender Dysphoria; Gender Identity; Transgender Persons; Sexual Behavior
PubMed: 36996732
DOI: 10.1016/j.psychres.2023.115176 -
The Lancet. Child & Adolescent Health Mar 2022Halting the rise in cardiometabolic risk factors in children and adolescents is crucial to curb the global burden of cardiovascular diseases. We aim to provide global,...
BACKGROUND
Halting the rise in cardiometabolic risk factors in children and adolescents is crucial to curb the global burden of cardiovascular diseases. We aim to provide global, regional, and national estimates of the prevalence of metabolic syndrome in children and adolescents to support the development of evidence-based prevention strategies.
METHODS
In this systematic review with modelling analysis, we searched PubMed, Embase, Africa Journal Online, and Global Index Medicus from database inception to Jan 30, 2021, with no restriction on language or geographical location. We included community-based and school-based cross-sectional studies and cross-sectional analysis of cohort studies that reported prevalence of metabolic syndrome in the general population of children (6-12 years) and adolescents (13-18 years). Only studies with a low risk of bias were considered. Eligible studies included at least 200 participants and used probabilistic-based sampling. Diagnosis of metabolic syndrome had to meet at least three of the following criteria: high systolic or diastolic blood pressure (≥90th percentile for age, sex, and height); waist circumference in at least the 90th percentile for age, sex, and ethnic group; fasting plasma glucose 5·6 mmol/L or greater; fasting plasma triglycerides 1·24 mmol/L or greater; and fasting plasma high density lipoprotein cholesterol 1·03 mmol/L or less. Independent investigators selected eligible studies and extracted relevant data. The primary outcome was a crude estimate of metabolic syndrome prevalence, assessed using a Bayesian hierarchical model.
FINDINGS
Our search yielded 6808 items, of which 169 studies were eligible for analysis, including 306 prevalence datapoints, with 550 405 children and adolescents from 44 countries in 13 regions. The between-study variance (τ) was 0·52 (95% CI 0·42-0·67), which could reflect the measurement of each component of the metabolic syndrome and covariates as sources of between-study heterogeneity. We estimated the global prevalence of metabolic syndrome in 2020 at 2·8% (95% uncertainty interval [UI] 1·4-6·7) for children and 4·8% (2·9-8·5) for adolescents, equating to around 25·8 (12·6-61·0) million children and 35·5 (21·3-63·0) million adolescents living with metabolic syndrome. In children, the prevalence of metabolic syndrome was 2·2% (95% UI 1·4-3·6) in high-income countries, 3·1% (2·5-4·3) in upper-middle-income countries, 2·6% (0·9-8·3) in lower-middle-income countries, and 3·5% (1·0-8·0) in low-income countries. In adolescents, the prevalence of metabolic syndrome was 5·5% (4·1-8·4) in high-income countries, 3·9% (3·1-5·4) in upper-middle-income countries, 4·5% (2·6-8·4) in lower-middle-income countries, and 7·0% (2·4-15·7) in low-income countries. Prevalence in children varied from 1·4% (0·6-3·1) in northwestern Europe to 8·2% (6·9-10·1) in Central Latin America. Prevalence for adolescents ranged from 2·9% (95% UI 2·6-3·3) in east Asia to 6·7% (5·9-8·3) in high-income English-speaking countries. The three countries with the highest prevalence estimates in children were Nicaragua (5·2%, 2·8-10·4), Iran (8·8%, 8·0-9·6), and Mexico (12·3%, 11·0-13·7); and the three countries with the highest prevalence estimates in adolescents were Iran (9·0%, 8·4-9·7), United Arab Emirates (9·8%, 8·5-10·3), and Spain (9·9%, 9·1-10·8).
INTERPRETATION
In 2020, about 3% of children and 5% of adolescents had metabolic syndrome, with some variation across countries and regions. The prevalence of metabolic syndrome was not consistently higher with increasing level of development, suggesting that the problem is not mainly driven by country wealth. The high number of children and adolescents living with metabolic syndrome globally highlights the urgent need for multisectoral interventions to reduce the global burden of metabolic syndrome and the conditions that lead to it, including childhood overweight and obesity.
FUNDING
None.
Topics: Adolescent; Age Distribution; Child; Cross-Sectional Studies; Female; Global Health; Humans; Male; Metabolic Syndrome; Models, Statistical; Prevalence
PubMed: 35051409
DOI: 10.1016/S2352-4642(21)00374-6 -
Environment International Aug 2021Mental health is an important public health issue globally. A potential link between heat exposure and mental health outcomes has been recognised in the scientific... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mental health is an important public health issue globally. A potential link between heat exposure and mental health outcomes has been recognised in the scientific literature; however, the associations between heat exposure (both high ambient temperatures and heatwaves) and mental health-related mortality and morbidity vary between studies and locations.
OBJECTIVE
To fill gaps in knowledge, this systematic review aims to summarize the epidemiological evidence and investigate the quantitative effects of high ambient temperatures and heatwaves on mental health-related mortality and morbidity outcomes, while exploring sources of heterogeneity.
METHODS
A systematic search of peer-reviewed epidemiological studies on heat exposure and mental health outcomes published between January 1990 and November 2020 was conducted using five databases (PubMed, Embase, Scopus, Web of Science and PsycINFO). We included studies that examined the association between high ambient temperatures and/or heatwaves and mental health-related mortality and morbidity (e.g. hospital admissions and emergency department visits) in the general population. A range of mental health conditions were defined using ICD-10 classifications. We performed random effects meta-analysis to summarize the relative risks (RRs) in mental health outcomes per 1 °C increase in temperature, and under different heatwaves definitions. We further evaluated whether variables such as age, sex, socioeconomic status, and climate zone may explain the observed heterogeneity.
RESULTS
The keyword search yielded 4560 citations from which we identified 53 high temperatures/heatwaves studies that comprised over 1.7 million mental health-related mortality and 1.9 million morbidity cases in total. Our findings suggest associations between heat exposures and a range of mental health-related outcomes. Regarding high temperatures, our meta-analysis of study findings showed that for each 1 °C increase in temperature, the mental health-related mortality and morbidity increased with a RR of 1.022 (95%CI: 1.015-1.029) and 1.009 (95%CI: 1.007-1.015), respectively. The greatest mortality risk was attributed to substance-related mental disorders (RR, 1.046; 95%CI: 0.991-1.101), followed by organic mental disorders (RR, 1.033; 95%CI: 1.020-1.046). A 1 °C temperature rise was also associated with a significant increase in morbidity such as mood disorders, organic mental disorders, schizophrenia, neurotic and anxiety disorders. Findings suggest evidence of vulnerability for populations living in tropical and subtropical climate zones, and for people aged more than 65 years. There were significant moderate and high heterogeneities between effect estimates in overall mortality and morbidity categories, respectively. Lower heterogeneity was noted in some subgroups. The magnitude of the effect estimates for heatwaves varied depending on definitions used. The highest effect estimates for mental health-related morbidity was observed when heatwaves were defined as "mean temperature ≥90th percentile for ≥3 days" (RR, 1.753; 95%CI: 0.567-5.421), and a significant effect was also observed when the definition was "mean temperature ≥95th percentile for ≥3 days", with a RR of 1.064 (95%CI: 1.006-1.123).
CONCLUSIONS
Our findings support the hypothesis of a positive association between elevated ambient temperatures and/or heatwaves and adverse mental health outcomes. This problem will likely increase with a warming climate, especially in the context of climate change. Further high-quality studies are needed to identify modifying factors of heat impacts.
Topics: Climate Change; Hot Temperature; Humans; Morbidity; Outcome Assessment, Health Care; Temperature
PubMed: 33799230
DOI: 10.1016/j.envint.2021.106533 -
Neurology Aug 2023Comprehensive guidelines for the diagnosis, prognosis, and treatment of disorders of consciousness (DoC) in pediatric patients have not yet been released. We aimed to... (Review)
Review
BACKGROUND AND OBJECTIVES
Comprehensive guidelines for the diagnosis, prognosis, and treatment of disorders of consciousness (DoC) in pediatric patients have not yet been released. We aimed to summarize available evidence for DoC with >14 days duration to support the future development of guidelines for children, adolescents and young adults aged 6 months-18 years.
METHODS
This scoping review was reported based on Preferred Reporting Items for Systematic reviews and Meta-Analyses-extension for Scoping Reviews guidelines. A systematic search identified records from 4 databases: PubMed, Embase, Cochrane Library, and Web of Science. Abstracts received 3 blind reviews. Corresponding full-text articles rated as "in-scope" and reporting data not published in any other retained article (i.e., no double reporting) were identified and assigned to 5 thematic evaluating teams. Full-text articles were reviewed using a double-blind standardized form. Level of evidence was graded, and summative statements were generated.
RESULTS
On November 9, 2022, 2,167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the past 5 years. Overall, 2,161 individuals met the inclusion criteria; female patients were 527 of 1,554 (33.9%) cases included, whose sex was identifiable. Of 132 articles, 57 (43.2%) were single case reports and only 5 (3.8%) clinical trials; the level of evidence was prevalently low (80/132; 60.6%). Most studies included neurobehavioral measures (84/127; 66.1%) and neuroimaging (81/127; 63.8%); 59 (46.5%) were mainly related to diagnosis, 56 (44.1%) to prognosis, and 44 (34.6%) to treatment. Most frequently used neurobehavioral tools included the Coma Recovery Scale-Revised, Coma/Near-Coma Scale, Level of Cognitive Functioning Assessment Scale, and Post-Acute Level of Consciousness scale. EEG, event-related potentials, structural CT, and MRI were the most frequently used instrumental techniques. In 29/53 (54.7%) cases, DoC improvement was observed, which was associated with treatment with amantadine.
DISCUSSION
The literature on pediatric DoCs is mainly observational, and clinical details are either inconsistently presented or absent. Conclusions drawn from many studies convey insubstantial evidence and have limited validity and low potential for translation in clinical practice. Despite these limitations, our work summarizes the extant literature and constitutes a base for future guidelines related to the diagnosis, prognosis, and treatment of pediatric DoC.
Topics: Adolescent; Humans; Female; Child; Consciousness; Consciousness Disorders; Coma; Prognosis; Randomized Controlled Trials as Topic
PubMed: 37308301
DOI: 10.1212/WNL.0000000000207473 -
The Cochrane Database of Systematic... May 2021Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications.
OBJECTIVES
To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020.
SELECTION CRITERIA
Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs).
DATA COLLECTION AND ANALYSIS
Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results.
MAIN RESULTS
Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants.
AUTHORS' CONCLUSIONS
Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.
Topics: Adolescent; Antidepressive Agents; Bias; Child; Citalopram; Depressive Disorder, Major; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Female; Fluoxetine; Humans; Male; Mirtazapine; Network Meta-Analysis; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Suicidal Ideation; Venlafaxine Hydrochloride; Vilazodone Hydrochloride; Vortioxetine
PubMed: 34029378
DOI: 10.1002/14651858.CD013674.pub2 -
Human Reproduction Update Nov 2023Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited.
OBJECTIVE AND RATIONALE
We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age-peri- or postmenopausal-with PCOS.
SEARCH METHODS
Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system.
OUTCOMES
The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies-published in 41 articles-were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD -0.60 (-0.76, -0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD -0.32 (-0.46, -0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)). Albeit myocardial infarction (OR 2.51 (1.08, 5.81)) and stroke (OR 1.75 (1.03, 2.99)) were more prevalent in women with PCOS than controls, the ORs for cardiovascular disease as a whole, coronary artery disease as a whole, breast cancer and age at menopause, were similar in patients and controls. When restricting meta-analysis to studies in which women with PCOS and controls had a similar mean BMI, the only difference that retained statistical significance was a decrease in HDL-cholesterol concentration in the former and, in the two studies in which postmenopausal women with PCOS and controls had similar BMI, patients presented with increased serum androgen concentrations, suggesting that hyperandrogenism persists after menopause, regardless of obesity.
WIDER IMPLICATIONS
Hyperandrogenism appeared to persist during the late-reproductive years and after menopause in women with PCOS. Most cardiometabolic comorbidities were driven by the frequent coexistence of weight excess and PCOS, highlighting the importance of targeting obesity in this population. However, the significant heterogeneity among included studies, and the overall low quality of the evidence gathered here, precludes reaching definite conclusions on the issue. Hence, guidelines derived from adequately powered prospective studies are definitely needed for appropriate management of these women.
Topics: Humans; Female; Middle Aged; Androgens; Polycystic Ovary Syndrome; Hyperandrogenism; Cross-Sectional Studies; Prospective Studies; Obesity; Menopause; Cholesterol
PubMed: 37353908
DOI: 10.1093/humupd/dmad015 -
Journal of Pediatric Urology Feb 2021Gender assignment in infants born with a difference in sexual development (DSD) remains one of the many difficult decisions faced by the multi-disciplinary treatment... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Gender assignment in infants born with a difference in sexual development (DSD) remains one of the many difficult decisions faced by the multi-disciplinary treatment team as some of these children develop gender identity disorder (GID) when they become adults. In this systematic review and meta-analysis we have analyzed the prevalence of GID in adolescent and adults with DSD. The secondary outcome of this review is to help physicians in appropriate sex assignment of DSD children so that development of GID in later life can be reduced.
METHODS
Pubmed/Index medicus were searched for "intersex" [All fields] OR "disorders of sexual differentiation AND "gender identity disorder OR gender dysphoria" [MeSH] for articles published between 2005 and 2020. Typical diagnoses included were congenital adrenal hyperplasia (CAH); complete androgen insensitivity syndrome (CAIS); partial androgen insensitivity syndrome (PAIS); 5 alpha reductase deficiency (5ARD); 17-hydroxysteroid dehydrogenase deficiency (17HSD); mixed gonadal dysgenesis (MGD) and complete gonadal dysgenesis (CGD). GID or gender dysphoria (a strong feeling of dissatisfaction about oneself as male or female) prevalence in DSD patients older than 12 years of age was extracted. Within each condition, GID percentage was compared between female and male rearing.
RESULTS
The I2statistics for prevalence of GID in DSD showed high heterogeneity with I2 of 93% (95% C.I 90-95%) among the 20 articles included. The overall prevalence of GID among those with DSD was 15% (95% C.I 13-17%). CAH reared females had 4% GID while CAH reared males had significantly higher GID at 15% (p = 0.0056). All CAIS patients were raised as females and the prevalence of GID was 1.7%. GID prevalence was 12% in PAIS raised as females while 25% in those raised as males with no significant difference (p = 0.134). GID was significantly high in 5ARD (53%) and 17HSD (53%) reared as females with half of them virilizing at puberty forcing a gender change. Among sex chromosome DSD 22% of those reared as females had GID while none in those raised as male with no significant difference.
CONCLUSIONS
GID is low in women with CAH, CAIS and CGD favoring female sex of rearing in these conditions. GID is high in women with 5ARD/17HSD favoring male sex of rearing in these conditions. GID is variable in PAIS or MGD and no recommendations on sex of rearing could be made in these conditions. Each DSD patient is unique and they warrant multi-disciplinary care and long term psycho sexual support.
Topics: Adolescent; Adult; Child; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Female; Gender Dysphoria; Gender Identity; Humans; Male; Sexual Development; Steroid Metabolism, Inborn Errors
PubMed: 33246831
DOI: 10.1016/j.jpurol.2020.11.017 -
Molecular Metabolism May 2020Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism,...
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechanisms have been implicated in the etiology of this heterogeneous endocrine disorder; hyperandrogenism at various developmental periods is proposed as a major driver of the metabolic and reproductive perturbations associated with PCOS. However, the current understanding of the pathophysiology of PCOS-associated metabolic disease is incomplete, and therapeutic strategies used to manage this syndrome's metabolic complications remain limited.
SCOPE OF REVIEW
This study is a systematic review of the potential etiopathogenic mechanisms of metabolic dysfunction frequently associated with PCOS, with special emphasis on the metabolic impact of androgen excess on different metabolic tissues and the brain. We also briefly summarize the therapeutic approaches currently available to manage metabolic perturbations linked to PCOS, highlighting current weaknesses and future directions.
MAJOR CONCLUSIONS
Androgen excess plays a prominent role in the development of metabolic disturbances associated with PCOS, with a discernible impact on key peripheral metabolic tissues, including the adipose, liver, pancreas, and muscle, and very prominently the brain, contributing to the constellation of metabolic complications of PCOS, from obesity to insulin resistance. However, the current understanding of the pathogenic roles of hyperandrogenism in metabolic dysfunction of PCOS and the underlying mechanisms remain largely incomplete. In addition, the development of more efficient, even personalized therapeutic strategies for the metabolic management of PCOS patients persists as an unmet need that will certainly benefit from a better comprehension of the molecular basis of this heterogeneous syndrome.
Topics: Adipose Tissue; Androgens; Animals; Bariatric Surgery; Female; Humans; Hyperandrogenism; Insulin Resistance; Metabolic Syndrome; Mice; Obesity; Polycystic Ovary Syndrome
PubMed: 32244180
DOI: 10.1016/j.molmet.2020.01.001 -
PLoS Medicine Sep 2020Globally, the number of refugees and asylum seekers has reached record highs. Past research in refugee mental health has reported wide variation in mental illness... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, the number of refugees and asylum seekers has reached record highs. Past research in refugee mental health has reported wide variation in mental illness prevalence data, partially attributable to methodological limitations. This systematic review aims to summarise the current body of evidence for the prevalence of mental illness in global refugee populations and overcome methodological limitations of individual studies.
METHODS AND FINDINGS
A comprehensive search of electronic databases was undertaken from 1 January 2003 to 4 February 2020 (MEDLINE, MEDLINE In-Process, EBM Reviews, Embase, PsycINFO, CINAHL, PILOTS, Web of Science). Quantitative studies were included if diagnosis of mental illness involved a clinical interview and use of a validated assessment measure and reported at least 50 participants. Study quality was assessed using a descriptive approach based on a template according to study design (modified Newcastle-Ottawa Scale). Random-effects models, based on inverse variance weights, were conducted. Subgroup analyses were performed for sex, sample size, displacement duration, visa status, country of origin, current residence, type of interview (interpreter-assisted or native language), and diagnostic measure. The systematic review was registered with PROSPERO (CRD) 42016046349. The search yielded a result of 21,842 records. Twenty-six studies, which included one randomised controlled trial and 25 observational studies, provided results for 5,143 adult refugees and asylum seekers. Studies were undertaken across 15 countries: Australia (652 refugees), Austria (150), China (65), Germany (1,104), Italy (297), Lebanon (646), Nepal (574), Norway (64), South Korea (200), Sweden (86), Switzerland (164), Turkey (238), Uganda (77), United Kingdom (420), and the United States of America (406). The prevalence of posttraumatic stress disorder (PTSD) was 31.46% (95% CI 24.43-38.5), the prevalence of depression was 31.5% (95% CI 22.64-40.38), the prevalence of anxiety disorders was 11% (95% CI 6.75-15.43), and the prevalence of psychosis was 1.51% (95% CI 0.63-2.40). A limitation of the study is that substantial heterogeneity was present in the prevalence estimates of PTSD, depression, and anxiety, and limited covariates were reported in the included studies.
CONCLUSIONS
This comprehensive review generates current prevalence estimates for not only PTSD but also depression, anxiety, and psychosis. Refugees and asylum seekers have high and persistent rates of PTSD and depression, and the results of this review highlight the need for ongoing, long-term mental health care beyond the initial period of resettlement.
Topics: Anxiety; Anxiety Disorders; Depression; Depressive Disorder; Female; Humans; Male; Mental Disorders; Mental Health; Prevalence; Refugees; Stress Disorders, Post-Traumatic
PubMed: 32956381
DOI: 10.1371/journal.pmed.1003337