-
The Cochrane Database of Systematic... Jun 2024Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy.
OBJECTIVES
To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction.
SEARCH METHODS
We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods.
MAIN RESULTS
We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor.
AUTHORS' CONCLUSIONS
Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.
Topics: Humans; Female; Dehydroepiandrosterone; Randomized Controlled Trials as Topic; Pregnancy; Testosterone; Reproductive Techniques, Assisted; Pregnancy Rate; Live Birth; Infertility, Female; Androgens; Bias; Abortion, Spontaneous; Ovulation Induction
PubMed: 38837771
DOI: 10.1002/14651858.CD009749.pub3 -
Frontiers in Endocrinology 2024Accumulating evidence suggests that the autism spectrum disorder (ASD) population exhibits altered hormone levels, including androgens. However, studies on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accumulating evidence suggests that the autism spectrum disorder (ASD) population exhibits altered hormone levels, including androgens. However, studies on the regulation of androgens, such as testosterone and dehydroepiandrosterone (DHEA), in relation to sex differences in individuals with ASD are limited and inconsistent. We conducted the systematic review with meta-analysis to quantitatively summarise the blood, urine, or saliva androgen data between individuals with ASD and controls.
METHODS
A systematic search was conducted for eligible studies published before 16 January 2023 in six international and two Chinese databases. We computed summary statistics with a random-effects model. Publication bias was assessed using funnel plots and heterogeneity using I statistics. Subgroup analysis was performed by age, sex, sample source, and measurement method to explain the heterogeneity.
RESULTS
17 case-control studies (individuals with ASD, 825; controls, 669) were assessed. Androgen levels were significantly higher in individuals with ASD than that in controls (SMD: 0.27, 95% CI: 0.06-0.48, =0.01). Subgroup analysis showed significantly elevated levels of urinary total testosterone, urinary DHEA, and free testosterone in individuals with ASD. DHEA level was also significantly elevated in males with ASD.
CONCLUSION
Androgen levels, especially free testosterone, may be elevated in individuals with ASD and DHEA levels may be specifically elevated in males.
Topics: Humans; Male; Androgens; Autism Spectrum Disorder; Case-Control Studies; Dehydroepiandrosterone; Testosterone; Female
PubMed: 38779452
DOI: 10.3389/fendo.2024.1371148 -
Behavioural Brain Research Jul 2024This systematic review aims to comprehensively explore the impact of psychostimulant substances on neurotrophic and inflammatory pathways, including brain-derived...
BACKGROUND
This systematic review aims to comprehensively explore the impact of psychostimulant substances on neurotrophic and inflammatory pathways, including brain-derived neurotrophic factor (BDNF), pro-BDNF, cortisol, dehydroepiandrosterone sulfate (DHEAS), thiobarbituric acid reactive substances (TBARS), interleukins, and the role of genetic factors. The study seeks to address existing gaps in the literature by providing a thorough evaluation of neurotrophic and inflammatory system alterations associated with different stages of psychostimulant dependence for a more nuanced understanding of substance use disorder (SUD) neurobiology.
METHODS
A systematic review was conducted in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. The research encompasses 50 studies with a participant pool totaling 6792 individuals using psychostimulant substances.
RESULTS
Key findings include diverse impacts of cocaine on BDNF levels, mainly consisting of their significant increase during withdrawal. In contrast, NGF showed an opposite behavior, reducing during withdrawal. Cortisol and DHEAS levels exhibited relevant increases after psychostimulant use, while TBARS showed conflicting results. Genetic investigations predominantly focused on the Val66Met polymorphism of the BDNF gene, revealing associations with susceptibility to stimulant addiction.
CONCLUSIONS
Neurotrophins and inflammatory molecules play a significant role in the pathophysiological mechanisms following psychostimulant use. A better understanding of their complex interplay could aid clinicians in identifying biomarkers of different disease stages. Moreover, clinical interventions designed to interfere with neurotrophic and inflammatory pathways could possibly lead to craving-modulatory strategies and reduce pathological neuronal and systemic consequences of psychostimulant use.
Topics: Humans; Biomarkers; Brain-Derived Neurotrophic Factor; Central Nervous System Stimulants; Hydrocortisone; Nerve Growth Factors; Oxidative Stress; Substance-Related Disorders
PubMed: 38761859
DOI: 10.1016/j.bbr.2024.115046 -
Journal of Bone and Mineral Research :... May 2024Adrenal adenomas/incidentalomas with mild autonomous cortisol secretion (MACS)/subclinical hypercortisolism (SH) are often associated with metabolic syndrome,...
Fracture risk and bone health in adrenal adenomas with mild autonomous cortisol secretion/subclinical Hypercortisolism: a systematic review, meta-analysis and meta-regression.
Adrenal adenomas/incidentalomas with mild autonomous cortisol secretion (MACS)/subclinical hypercortisolism (SH) are often associated with metabolic syndrome, glucocorticoid-induced osteoporosis and fractures. In this background, the present systematic review and meta-analysis aimed to collate the available evidence and provide a summary of effect of MACS/SH on bone health in terms of fractures, osteoporosis/osteopenia, microarchitecture, and bone turnover. PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched for observational studies reporting prevalence of fractures, osteoporosis/osteopenia or data on bone microarchitecture/bone turnover markers (BTMs). Following literature search, 16 observational studies were included. Pooled prevalence of any fractures (vertebral and non-vertebral), vertebral fractures and osteoporosis/osteopenia in MACS/SH were 43% [95% confidence intervals (CI): 23%, 62%], 45% (95% CI: 22%, 68%) and 50% (95% CI: 33%, 66%), respectively. On meta-regression, age, sex, 24-hour urinary free cortisol and dehydroepiandrosterone-sulfate did not predict fracture risk. The likelihood of any fractures [odds ratio (OR) 1.61; 95% CI: 1.18, 2.20; p = 0.0026], vertebral fractures (OR 2.10; 95% CI: 1.28, 3.45; p = 0.0035) and osteoporosis/osteopenia (OR 1.46; 95% CI: 1.15, 1.85; p = 0.0018) was significantly higher in adrenal adenomas and MACS/SH than non-functional adrenal adenomas. Subjects with MACS/SH had significantly lower bone mineral density (BMD) at lumbar spine [mean difference (MD) -0.07 gm/cm2; 95% CI: -0.11, -0.03; p = 0.0004) and femoral neck (MD -0.05 gm/cm2; 95% CI: -0.08, -0.02; p = 0.0045) than their non-functional counterparts. Limited data showed no significant difference in BTMs. Publication bias was observed in the pooled prevalence of any fractures, vertebral fractures and pooled MD of femoral neck BMD. To conclude, people with adrenal adenomas/incidentalomas and MACS/SH are at 1.5 to 2-fold higher likelihood of fractures and osteoporosis/osteopenia compared to non-functional adrenal adenomas and should routinely be screened for bone disease. Nevertheless, considering the modest sample size of studies and evidence of publication bias, larger and high-quality studies are required (CRD42023471045).
PubMed: 38703381
DOI: 10.1093/jbmr/zjae067 -
Stress and Health : Journal of the... Mar 2024Ageing and chronic stress have been linked to reduced telomere length (TL) in mixed-age groups. Whether stress response components are linked to TL during the... (Review)
Review
Exploring the interplay of psychological and biological components of stress response and telomere length in the transition from middle age to late adulthood: A systematic review.
Ageing and chronic stress have been linked to reduced telomere length (TL) in mixed-age groups. Whether stress response components are linked to TL during the midlife-to-late adulthood transition remains unclear. Our study aimed to synthesise evidence on the relationship between psychological and biological components of stress response on TL in middle-aged and older adults. We conducted a systematic review of studies obtained from six databases (PubMed, CINAHL, EMBASE, PsycINFO, Web of Science, and Scopus) and evaluated by two independent reviewers. Original research measuring psychological and biological components of stress response and TL in human individuals were included. From an initial pool of 614 studies, 15 were included (n = 9446 participants). Synthesis of evidence showed that higher psychological components of the stress response (i.e., global perceived stress or within a specific life domain and cognitive appraisal to social-evaluative stressors) were linked to shorter TL, specifically in women or under major life stressors. For the biological stress response, cortisol, dehydroepiandrosterone sulphate and IGF-1/cortisol imbalance, IL-6, MCP-1, blood pressure, and heart rate presented a significant association with TL, but this relationship depended on major life stressors and the stress context (manipulated vs. non-manipulated conditions). This comprehensive review showed that psychological and biological components of the stress response are linked to shorter TL, but mainly in women or those under a major life stressor and stress-induced conditions. The interaction between stressor attributes and psychological and biological reactions in the transition from middle to late adulthood still needs to be fully understood, and examining it is a critical step to expanding our understanding of stress's impact on ageing trajectories.
PubMed: 38442010
DOI: 10.1002/smi.3389 -
Environmental Pollution (Barking, Essex... Mar 2024The biological pathways linking lead exposure to adverse outcomes are beginning to be understood. Rodent models suggest lead exposure induces dysfunction within the... (Review)
Review
The biological pathways linking lead exposure to adverse outcomes are beginning to be understood. Rodent models suggest lead exposure induces dysfunction within the hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid regulation, a primary physiological stress response system. Over time, HPA axis and glucocorticoid dysfunction has been associated with adverse neurocognitive and cardiometabolic health, much like lead exposure. This systematic review utilized PRISMA guidelines to synthesize the literature regarding associations between lead exposure and downstream effector hormones of the HPA axis, including cortisol, a glucocorticoid, and dehydroepiandrosterone (DHEA), a glucocorticoid antagonist. We additionally determined the state of the evidence regarding lead exposure and allostatic load, a measure of cumulative body burden resultant of HPA axis and glucocorticoid dysfunction. A total of 18 articles were included in the review: 16 assessed cortisol or DHEA and 3 assessed allostatic load. Generally, the few available child studies suggest a significant association between early life lead exposure and altered cortisol, potentially suggesting the impact of developmental exposure. In adulthood, only cross sectional studies were available. These reported significant associations between lead and reduced cortisol awakening response and increased cortisol reactivity, but few associations with fasting serum cortisol. Two studies reported significant associations between increasing lead exposure and allostatic load in adults and another between early life lead exposure and adolescent allostatic load. The paucity of studies examining associations between lead exposure and allostatic load or DHEA and overall heterogeneity of allostatic load measurements limit conclusions. However, these findings cautiously suggest associations between lead and dysregulation of physiological stress pathways (i.e., glucocorticoids) as seen through cortisol measurement in children and adults. Future research would help to elucidate these associations and could further examine the physiological stress pathway as a mediator between lead exposure and detrimental health outcomes.
Topics: Adult; Child; Adolescent; Humans; Glucocorticoids; Hydrocortisone; Lead; Hypothalamo-Hypophyseal System; Cross-Sectional Studies; Pituitary-Adrenal System; Stress, Physiological; Dehydroepiandrosterone; Stress, Psychological
PubMed: 38281572
DOI: 10.1016/j.envpol.2024.123329 -
Food & Function Feb 2024: A large number of recent studies have reported on the use of antioxidants in patients with polycystic ovary syndrome (PCOS). This study aimed to evaluate the... (Meta-Analysis)
Meta-Analysis Review
: A large number of recent studies have reported on the use of antioxidants in patients with polycystic ovary syndrome (PCOS). This study aimed to evaluate the antioxidant effects on PCOS. : We searched PubMed, Embase, Web of Science, and The Cochrane Library to identify randomized controlled trials investigating the use of antioxidants in treating PCOS. Statistical analysis was performed using Review Manager 5.4. Stata17.0 software was used to conduct sensitivity analyses. : This meta-analysis included 49 articles and 62 studies. The sample comprised 1657 patients with PCOS from the antioxidant group and 1619 with PCOS from the placebo group. The meta-analysis revealed that the fasting blood glucose levels [standardized mean difference (SMD): -0.31, 95% confidence interval (CI): -0.39 to -0.22, < 0.00001], the homeostatic model assessment of insulin resistance (SMD: -0.68, 95% CI: -0.87 to -0.50], < 0.00001), and insulin levels (SMD: -0.68, 95% CI: -0.79 to -0.58, < 0.00001) were significantly lower in patients with PCOS taking antioxidants than those in the placebo group. Further, total cholesterol levels (SMD: -0.38, 95% CI: -0.56 to -0.20, < 0.001), low-density lipoprotein cholesterol levels (SMD: -0.24, 95% CI: -0.37 to -0.10, = 0.0008), and very low-density lipoprotein levels (SMD: -0.53, 95% CI: -0.65 to -0.41, < 0.00001) were lower in patients with PCOS taking antioxidant supplements compared with the placebo group. Total testosterone (TT) level (SMD: -0.78, 95% CI: -1.15 to -0.42, < 0.0001), dehydroepiandrosterone level (SMD: -0.42, 95% CI: -0.58 to -0.25, < 0.00001), and mean standard deviation modified Ferriman-Gallway (MF-G scores) (SMD: -0.63, 95% CI: -0.98 to -0.28, = 0.0004) were lower in patients taking antioxidant supplements. C-reactive protein (CRP) levels (SMD: -0.48, 95% CI: -0.63 to -0.34, < 0.000001), body mass index [mean difference (MD): -0.27, 95% CI: -0.50 to -0.03, = 0.03], weight (MD: -0.73, 95% CI: -1.35 to -0.11, = 0.02), and diastolic blood pressure (MD: -3.78, 95% CI: -6.30 to -1.26, = 0.003) were significantly lower. Moreover, the levels of sex hormone-binding protein (SMD: 0.23, 95% CI: 0.07-0.38, = 0.004), high-density lipoprotein cholesterol (SMD: 0.11, 95% CI: 0.01-0.20, = 0.03), total antioxidant capacity (SMD: 0.59, 95% CI: 0.31-0.87, < 0.0001), and quantitative insulin sensitivity index (SMD: 0.01, 95% CI: 0.01-0.02, < 0.00001) were higher in patients with PCOS who took antioxidant supplements compared with the placebo group. Antioxidant supplements did not affect other analyzed parameters in these patients, including follicle-stimulating hormone, free androgen index, nitric oxide, glutathione, malondialdehyde, and diastolic blood pressure. : Antioxidants are beneficial in treating PCOS. Our study might provide a new treatment strategy for patients with clinical PCOS. We hope that more high-quality studies evaluating the effects of antioxidants on patients with PCOS will be conducted in the future. : https://www.crd.york.ac.uk/prospero/, identifier CRD42023448088.
Topics: Female; Humans; Antioxidants; Polycystic Ovary Syndrome; Dietary Supplements; Lipoproteins, LDL; Cholesterol
PubMed: 38251706
DOI: 10.1039/d3fo02824k -
Reproductive Sciences (Thousand Oaks,... May 2024Obesity, insulin resistance, and hyperandrogenemia are commonly seen in women with polycystic ovary syndrome (PCOS), and these three conditions form a vicious cycle... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obesity, insulin resistance, and hyperandrogenemia are commonly seen in women with polycystic ovary syndrome (PCOS), and these three conditions form a vicious cycle leading to reproductive and metabolic abnormalities. Metformin improves the symptoms of PCOS by increasing insulin sensitivity but is not therapeutically optimal. Recent studies have reported that sodium-glucose co-transporter protein receptor inhibitors improve insulin resistance and reduce the weight of patients with PCOS. We performed a meta-analysis to assess the influence of sodium-glucose co-transporter protein-2 (SGLT2) inhibitors on anthropometric, glycolipid metabolism and reproductive outcomes after therapy of overweight/obese women with PCOS.
METHODS
We searched the relevant literature published up to April 2023. Information on the effect of SGLT2 inhibitors on overweight/obese patients with PCOS was extracted independently by two reviewers. Review Manager 5.3 was used for meta-analysis.
RESULTS
Five randomized controlled trials that met our criteria were retrieved. Our meta-analysis demonstrated that in overweight/obese patients with PCOS, SGLT2 inhibitors treatment was significantly superior to metformin treatment in terms of reducing body weight (P = 0.02, I = 36%), decreasing dehydroepiandrosterone sulfate concentrations [SMD = -0.42, 95% CI (-0.76, -0.07), I = 22%, P = 0.02], and reducing the incidence of nausea [RR = 0.35, 95% CI (0.21, 0.60), I = 71%, P = 0.0001].
CONCLUSIONS
SGLT2 inhibitors are a possible alternative therapy for treating overweight/obese women with PCOS who do not respond favorably to metformin treatment. However, further large randomized controlled trials and cost-effectiveness analyses are warranted to guide the implementation of SGLT2 inhibitors treatment in this population.
Topics: Humans; Polycystic Ovary Syndrome; Female; Sodium-Glucose Transporter 2 Inhibitors; Obesity; Overweight; Metformin; Hypoglycemic Agents; Randomized Controlled Trials as Topic
PubMed: 38057530
DOI: 10.1007/s43032-023-01415-5 -
Mediterranean Journal of Rheumatology Sep 2023Dehydroepiandrosterone (DHEA) is an adrenal hormone used to treat rheumatic conditions such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), rheumatoid...
BACKGROUND
Dehydroepiandrosterone (DHEA) is an adrenal hormone used to treat rheumatic conditions such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), rheumatoid arthritis (RA) with controversial results.
AIM
To review the results of DHEA use in rheumatic diseases.
METHODS
PubMed, Scielo, Scopus, and Embase databases were systematically searched for articles on the treatment of rheumatic diseases with DHEA between 1966 and April 2023.
RESULTS
Twenty-one studies were identified: 13 in SLE, 5 in SS, 2 in RA, and 1 in fibromyalgia. DHEA use in SLE has shown a mild to moderate effect on disease activity, a positive effect on bone mineral density (BMD), and improved fatigue. The studies on SS showed a decrease in symptoms of dry mouth, but its performance did not differ from placebo in disease activity. In RA, a questionable effect on disease activity was noted. The only study on fibromyalgia failed to show any improvement. The drug was well tolerated; mild androgenic effects were the most common complaints.
CONCLUSION
DHEA seems to have a place in SLE treatment, where it improves BMD and disease activity. The use in RA, SS, and FM is questionable.
PubMed: 37941864
DOI: 10.31138/mjr.20230825.dd -
Frontiers in Nutrition 2023Inconsistent data suggest that flaxseed supplementation may have a role in sex hormones. We aimed to carry out a systematic review and meta-analysis of randomized...
Inconsistent data suggest that flaxseed supplementation may have a role in sex hormones. We aimed to carry out a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating effects of flaxseed supplementation on sex hormone profile. PubMed, Scopus, Embase, Cochrane Library, Web of Science databases, and Google Scholar were searched up to March 2023. Standardized mean difference (SMD) was pooled using a random-effects model. Sensitivity analysis, heterogeneity, and publication bias were reported using standard methods. The quality of each study was evaluated with the revised Cochrane risk-of-bias tool for randomized trials, known as RoB 2. Finding from ten RCTs revealed that flaxseed supplementation had no significant alteration in follicle-stimulating hormone (FSH) (SMD: -0.11; 95% CI: -0.87, 0.66: = 0.783), sex hormone-binding globulin (SHBG) (SMD: 0.35; 95% CI: -0.02, 0.72; = 0.063), total testosterone (TT) levels (SMD: 0.17; 95% CI: -0.07, 0.41; = 0.165), free androgen index (FAI) (SMD = 0.11, 95% CI: -0.61, 0.83; = 0.759), and dehydroepiandrosterone sulfate (DHEAS) (SMD: 0.08, 95%CI: -0.55, 0.72, = 0.794). Flaxseed supplementation had no significant effect on sex hormones in adults. Nevertheless, due to the limited included trials, this topic is still open and needs further studies in future RCTs.
PubMed: 37927501
DOI: 10.3389/fnut.2023.1222584