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The Cochrane Database of Systematic... Mar 2020Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency in children. In over 90% of cases, 21-hydroxylase enzyme deficiency is found which is caused by mutations in the 21-hydroxylase gene. Managing individuals with CAH due to 21-hydroxylase deficiency involves replacing glucocorticoids with oral glucocorticoids (including prednisolone and hydrocortisone), suppressing adrenocorticotrophic hormones and replacing mineralocorticoids to prevent salt wasting. During childhood, the main aims of treatment are to prevent adrenal crises and to achieve normal stature, optimal adult height and to undergo normal puberty. In adults, treatment aims to prevent adrenal crises, ensure normal fertility and to avoid the long-term consequences of glucocorticoid use. Current glucocorticoid treatment regimens can not optimally replicate the normal physiological cortisol level and over-treatment or under-treatment is often reported.
OBJECTIVES
To compare and determine the efficacy and safety of different glucocorticoid replacement regimens in the treatment of CAH due to 21-hydroxylase deficiency in children and adults.
SEARCH METHODS
We searched the Cochrane Inborn Errors of Metabolism Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews, and trial registries (ClinicalTrials.gov and WHO ICTRP). Date of last search of trials register: 24 June 2019.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing different glucocorticoid replacement regimens for treating CAH due to 21-hydroxylase deficiency in children and adults.
DATA COLLECTION AND ANALYSIS
The authors independently extracted and analysed the data from different interventions. They undertook the comparisons separately and used GRADE to assess the quality of the evidence.
MAIN RESULTS
Searches identified 1729 records with 43 records subject to further examination. After screening, we included five RCTs (six references) with a total of 101 participants and identified a further six ongoing RCTs. The number of participants in each trial varied from six to 44, with participants' ages ranging from 3.6 months to 21 years. Four trials were of cross-over design and one was of parallel design. Duration of treatment ranged from two weeks to six months per treatment arm with an overall follow-up between six and 12 months for all trials. Overall, we judged the quality of the trials to be at moderate to high risk of bias; with lack of methodological detail leading to unclear or high risk of bias judgements across many of the domains. All trials employed an oral glucocorticoid replacement therapy, but with different daily schedules and dose levels. Three trials compared different dose schedules of hydrocortisone (HC), one three-arm trial compared HC to prednisolone (PD) and dexamethasone (DXA) and one trial compared HC with fludrocortisone to PD with fludrocortisone. Due to the heterogeneity of the trials and the limited amount of evidence, we were unable to perform any meta-analyses. No trials reported on quality of life, prevention of adrenal crisis, presence of osteopenia, presence of testicular or ovarian adrenal rest tumours, subfertility or final adult height. Five trials (101 participants) reported androgen normalisation but using different measurements (very low-quality evidence for all measurements). Five trials reported 17 hydroxyprogesterone (17 OHP) levels, four trials reported androstenedione, three trials reported testosterone and one trial reported dehydroepiandrosterone sulphate (DHEAS). After four weeks, results from one trial (15 participants) showed a high morning dose of HC or a high evening dose made little or no difference in 17 OHP, testosterone, androstenedione and DHEAS. One trial (27 participants) found that HC and DXA treatment suppressed 17 OHP and androstenedione more than PD treatment after six weeks and a further trial (eight participants) reported no difference in 17 OHP between the five different dosing schedules of HC at between four and six weeks. One trial (44 participants) comparing HC and PD found no differences in the values of 17 OHP, androstenedione and testosterone at one year. One trial (26 participants) of HC versus HC plus fludrocortisone found that at six months 17 OHP and androstenedione levels were more suppressed on HC alone, but there were no differences noted in testosterone levels. While no trials reported on absolute final adult height, we reported some surrogate markers. Three trials reported on growth and bone maturation and two trials reported on height velocity. One trial found height velocity was reduced at six months in 26 participants given once daily HC 25 mg/m²/day compared to once daily HC 15 mg/m²/day (both groups also received fludrocortisone 0.1 mg/day), but as the quality of the evidence was very low we are unsure whether the variation in HC dose caused the difference. There were no differences noted in growth hormone or IGF1 levels. The results from another trial (44 participants) indicate no difference in growth velocity between HC and PD at one year (very low-quality evidence), but this trial did report that once daily PD treatment may lead to better control of bone maturation compared to HC in prepubertal children and that the absolute change in bone age/chronological age ratio was higher in the HC group compared to the PD group.
AUTHORS' CONCLUSIONS
There are currently limited trials comparing the efficacy and safety of different glucocorticoid replacement regimens for treating 21-hydroxylase deficiency CAH in children and adults and we were unable to draw any firm conclusions based on the evidence that was presented in the included trials. No trials included long-term outcomes such as quality of life, prevention of adrenal crisis, presence of osteopenia, presence of testicular or ovarian adrenal rest tumours, subfertility and final adult height. There were no trials examining a modified-release formulation of HC or use of 24-hour circadian continuous subcutaneous infusion of hydrocortisone. As a consequence, uncertainty remains about the most effective form of glucocorticoid replacement therapy in CAH for children and adults. Future trials should include both children and adults with CAH. A longer duration of follow-up is required to monitor biochemical and clinical outcomes.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Dexamethasone; Glucocorticoids; Humans; Infant; Prednisolone; Quality of Life; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32190901
DOI: 10.1002/14651858.CD012517.pub2 -
Bosnian Journal of Basic Medical... Aug 2020The functions of androgen and connexin in the mammalian female reproductive system are suggested to be related. Previous research has shown that androgen affects...
The functions of androgen and connexin in the mammalian female reproductive system are suggested to be related. Previous research has shown that androgen affects connexin expression in the female reproductive system, altering its function. However, no definitive conclusion on their cause-effect relationship has been drawn yet. In addition, a high prevalence of women with polycystic ovary syndrome (PCOS), who are characterized by elevated androgen levels and failure of ovulation, has prompted the studies on the relationship between androgen and connexin in the ovaries. This systematic review aims to investigate the effect of androgen on connexin expression in the mammalian female reproductive system. The literature search was conducted using the MEDLINE via EBSCOhost and the Scopus database and the following keywords: "androgen" or "testosterone" or "androgen blocker" or "anti-androgen" or "androstenedione" or "dehydroepiandrosterone" or "flut-amide AND connexin" or "gap junction" or "cell junction". We only considered in vitro and in vivo studies that involved treatment by androgen or androgen receptor blockers and measured connexin expression as one of the parameters. Our review showed that the exposure to androgen or androgen blocker affects connexin expression but not its localization in the mammalian ovary. However, it is not clear whether androgen downregulates or upregulates connexin expression.
Topics: Androgen Antagonists; Androgens; Animals; Connexins; Female; Genitalia, Female; Humans; Mammals; Polycystic Ovary Syndrome; Receptors, Androgen
PubMed: 31881167
DOI: 10.17305/bjbms.2019.4501 -
Clinical Oral Investigations Jan 2020The purpose of this review was to provide a novel perspective utilizing an assessment of biomarkers to evaluate the impact of stress-related disorders on the progression...
OBJECTIVES
The purpose of this review was to provide a novel perspective utilizing an assessment of biomarkers to evaluate the impact of stress-related disorders on the progression of periodontal disease and evaluate the growing body of evidence of stress as a risk indicator for periodontal disease progression.
METHODS
Cross-sectional, case-control, and biomarker studies associating psychological disorders and periodontal disease were included in the literature search. Computational studies, animal studies, reviews, and studies lacking healthy controls were excluded. Electronic and manual literature searches were conducted by two independent reviewers in several databases as well as a manual search for relevant articles published up to January 2018.
RESULTS
Twenty-six articles fulfilled the inclusion criteria and were included in the qualitative synthesis. Relationships between stress-related disorders and serum and salivary biomarkers such as cortisol, dehydroepiandrosterone (DHEA), chromogranin A (CgA), and pro-inflammatory cytokines were identified.
CONCLUSIONS
The use of salivary pro-inflammatory cytokines alone is not sufficient for the identification of periodontal disease severity/progression with or without the presence of stress-associated diseases. Keeping in mind the limitations of this review, a positive qualitative correlation was observed in the literature among stress-related biomarkers and the severity of periodontal disease. This correlation may serve as an important reporter of patient susceptibility for periodontal breakdown in the future.
CLINICAL RELEVANCE
Stress-related disorders should be included in the list of globally screened diseases because it can change the biochemistry of both the local periodontal microenvironment as well as the global systemic inflammatory burden.
Topics: Adult; Animals; Cross-Sectional Studies; Depression; Humans; Inflammation; Periodontal Diseases; Psychological Distress; Risk Factors
PubMed: 31677052
DOI: 10.1007/s00784-019-03089-3 -
Metabolites Sep 2019Steroidomics, an analytical technique for steroid biomarker mining, has received much attention in recent years. This systematic review and functional analysis,... (Review)
Review
Steroidomics, an analytical technique for steroid biomarker mining, has received much attention in recent years. This systematic review and functional analysis, following the PRISMA statement, aims to provide a comprehensive review and an appraisal of the developments and fundamental issues in steroid high-throughput analysis, with a focus on cancer research. We also discuss potential pitfalls and proposed recommendations for steroidomics-based clinical research. Forty-five studies met our inclusion criteria, with a focus on 12 types of cancer. Most studies focused on cancer risk prediction, followed by diagnosis, prognosis, and therapy monitoring. Prostate cancer was the most frequently studied cancer. Estradiol, dehydroepiandrosterone, and cortisol were mostly reported and altered in at least four types of cancer. Estrogen and estrogen metabolites were highly reported to associate with women-related cancers. Pathway enrichment analysis revealed that steroidogenesis; androgen and estrogen metabolism; and androstenedione metabolism were significantly altered in cancers. Our findings indicated that estradiol, dehydroepiandrosterone, cortisol, and estrogen metabolites, among others, could be considered oncosteroids. Despite noble achievements, significant shortcomings among the investigated studies were small sample sizes, cross-sectional designs, potential confounding factors, and problematic statistical approaches. More efforts are required to establish standardized procedures regarding study design, analytical procedures, and statistical inference.
PubMed: 31546652
DOI: 10.3390/metabo9100199 -
Frontiers in Aging Neuroscience 2019Previous studies found inconsistent results for the relationship between Alzheimer's disease and the levels of dehydroepiandrosterone and dehydroepiandrosterone...
Previous studies found inconsistent results for the relationship between Alzheimer's disease and the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate. This study performed a systematic review and meta-analysis to evaluate previous studies' results on this relationship. Studies related to this outcome were obtained using a systematic search from the electronic databases of PubMed, Embase, Web of Science, and Psyc-ARTICLES in March 2018. The random-effects model was used to measure the strength of the association between Alzheimer's disease and the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate, using the standardized mean difference. Thirty-one eligible studies were included in the final analysis. There was no statistically significant association between the level of dehydroepiandrosterone and Alzheimer's disease (standardized mean difference: 0.51, 95% confidence interval: -0.44 to 1.45, = 1.06, = 0.29). On the other hand, lower level dehydroepiandrosterone sulfate was observed in patients with Alzheimer's disease than in controls (standardized mean difference: -0.69, 95% confidence interval: -1.17 to -0.22, = -2.84, < 0.01). Decreased dehydroepiandrosterone sulfate concentrations may be an important indicator for Alzheimer's disease, although whether dehydroepiandrosterone sulfate could be used as a diagnostic tool requires further research.
PubMed: 30983988
DOI: 10.3389/fnagi.2019.00061 -
Medical Science Monitor : International... Jan 2019BACKGROUND Currently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND Currently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the effect of statins on serum or plasma levels of dehydroepiandrosterone (DHEA) in women with PCOS. MATERIAL AND METHODS Databases that were searched included PubMed, Embase, and the Cochrane Library from their inception to August of 2018. Published randomized controlled trials (RCTs) were identified that evaluated the impact of statins on plasma DHEA levels in women with PCOS. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. A random-effects model was used to analyze the pooled results. RESULTS Meta-analysis was performed on data from ten published studies that included 735 patients and showed that statin treatment could significantly reduce plasma DHEA levels when compared with controls (SMD, -0.43; 95% CI, -0.81-0.06; p=0.02; I²=82%). Statins were significantly more effective than placebo in reducing the levels of DHEAs. Subgroup analysis based on statin type showed that atorvastatin significantly reduced DHEA levels (SMD, -0.63; 95% CI, -1.20 - -0.05; p=0.03; I²=38%) but simvastatin did not significantly reduce DHEA levels (SMD: -0.14; 95% CI, -0.49-0.28; p=0.43; I²=77%). Subgroup analysis based on duration of treatment showed no significant difference between 12 weeks of statin treatment (SMD, -0.61; 95% CI, -1.23-0.02; p=0.06; I²=85%) and 24 weeks (SMD, -0.34; 95% CI -0.95-0.28; p=0.29; I²=83%). CONCLUSIONS Meta-analysis showed that statins significantly reduced the levels of DHEA when compared with placebo in patients with PCOS.
Topics: Adult; Atorvastatin; China; Dehydroepiandrosterone; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Middle Aged; Polycystic Ovary Syndrome; Simvastatin
PubMed: 30698163
DOI: 10.12659/MSM.914128 -
Journal of Comorbidity 2018Multimorbidity is the co-occurrence of two or more diseases in the same individual. One method to identify this condition at an early stage is the use of specific... (Review)
Review
BACKGROUND
Multimorbidity is the co-occurrence of two or more diseases in the same individual. One method to identify this condition at an early stage is the use of specific markers for various combinations of morbidities. Nonetheless, evidence related to physiological markers in multimorbidity is limited.
OBJECTIVE
The aim was to perform a systematic review to identify physiological markers associated with multimorbidity.
DESIGN
Articles available on PubMed, Register of Controlled Trials, Academic Search Premier, CINAHL, Scopus, SocINDEX, Web of Science, LILACS, and SciELO, from their inception to May 2018, were systematically searched and reviewed. The project was registered in PROSPERO under the number CRD42017055522.
RESULTS
The systematic search identified 922 papers. After evaluation, 18 articles were included in the full review reporting at least one physiological marker in coexisting diseases or which are strongly associated with the presence of multimorbidity in the future. Only five of these studies examined multimorbidity in general, identifying five physiological markers associated with multimorbidity, namely, dehydroepiandrosterone sulfate (DHEAS), interleukin 6 (IL-6), C-reactive protein (CRP), lipoprotein (Lp), and cystatin C (Cyst-C).
CONCLUSIONS
There is a paucity of studies related to physiological markers in multimorbidity. DHEAS, IL-6, CRP, Lp, and Cyst-C could be the initial focus for further investigation of physiological markers related to multimorbidity.
PubMed: 30364915
DOI: 10.1177/2235042X18806986 -
JBRA Assisted Reproduction Nov 2018The aim of this review is to determine if the use of DHEA increases the likelihood of success in patients with POR. We searched MEDLINE and EMBASE using the terms "DHEA... (Meta-Analysis)
Meta-Analysis
The aim of this review is to determine if the use of DHEA increases the likelihood of success in patients with POR. We searched MEDLINE and EMBASE using the terms "DHEA and diminished ovarian reserve", "DHEA and poor response", "DHEA and premature ovarian aging". A fixed effects model was used and Peto's method to get the odds ratio (OR) with 95% confidence intervals (CI 95%). For quantitative variables, Cohen's method was used to present the standardized mean differences (SMD) with their corresponding confidence intervals. Only five studied fulfilled the selection criteria. DHEA was administered in 25 mg doses, three times a day. In all studies, the authors corrected for the presence of confounding variables such as partner's age, infertility diagnosis and number of transferred embryos. The meta-analysis of the five selected studies assessed a total of 910 patients, who underwent IVF/ICSI, of which 413 had received DHEA. DHEA use was associated with a significant increase in pregnancy likelihood (OR 1.8, CI 95% 1.29 to 2.51, =0.001). When analyzing the association between DHEA use and the likelihood of abortion, we found low heterogeneity between studies (I=0.0%) and the use of DHEA to be associated to a significant reduction in the likelihood of abortion (OR 0.25, CI 0.07 to 0.95; =0.045). Analysis of the association of DHEA with average oocyte retrieval showed high variability between studies (I2=98.6%), as well as no association between DHEA use and the number of oocytes retrieved (SMD -0.01, CI 95% -0.16 to 0.13; <0.05).
Topics: Adult; Dehydroepiandrosterone; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Oocyte Retrieval; Ovarian Reserve; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic; Treatment Outcome
PubMed: 30125071
DOI: 10.5935/1518-0557.20180046 -
Menopause (New York, N.Y.) Jan 2019This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women with premature ovarian failure and to establish if there is evidence of diminished androgen levels in these women.
METHODS
Various Internet sources of PubMed, Cochrane library, and Medline were searched systematically until February, 2018. Out of a pool of 2,461 studies, after applying the inclusion/exclusion criterion, 14, 8, 10, and 9 studies were chosen for testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin, respectively, for this meta-analysis. The effect measure was the standardized mean difference with 95% confidence interval (95% CI) in a random-effects model.
RESULTS
The testosterone concentrations in premature ovarian insufficiency were compared with fertile controls: stamdard mean difference (IV, random, 95% CI) -0.73 [-0.99, -0.46], P value < 0.05. The dehydroepiandrosterone sulfate concentrations in premature ovarian insufficiency compared to fertile controls: standard mean difference (IV, random, 95% CI) -0.65 [-0.92, -0.37], P value < 0.05. Androstenedione in premature ovarian insufficiency were compared with fertile controls: standard mean difference (IV, random, 95% CI) -1.09 [-1.71, -0.48], P value < 0.05. Sex hormone-binding globulin levels did not show statistical significance. The dehydroepiandrosterone sulfate levels were reduced in premature ovarian insufficiency cases, but still showed a higher level than in postmenopausal women.
CONCLUSIONS
Women with premature ovarian insufficiency are at risk for decreased concentrations of testosterone, dehydroepiandrosterone sulfate, and androstenedione. Dehydroepiandrosterone sulfate levels were more reduced in postmenopausal controls when compared with premature ovarian insufficiency cases.
Topics: Adult; Androgens; Androstenedione; Dehydroepiandrosterone Sulfate; Female; Fertility; Humans; Menopause, Premature; Middle Aged; Postmenopause; Primary Ovarian Insufficiency; Sex Hormone-Binding Globulin; Testosterone; Women's Health; Young Adult
PubMed: 29994966
DOI: 10.1097/GME.0000000000001161 -
The Journal of Nutrition, Health & Aging 2018The objective of this study was to perform a systematic review to investigate the effects protein, essential amino acids (EAA), β-hydroxy β-methylbutyrate (HMB),...
Effects of Protein, Essential Amino Acids, B-Hydroxy B-Methylbutyrate, Creatine, Dehydroepiandrosterone and Fatty Acid Supplementation on Muscle Mass, Muscle Strength and Physical Performance in Older People Aged 60 Years and Over. A Systematic Review on the Literature.
OBJECTIVES
The objective of this study was to perform a systematic review to investigate the effects protein, essential amino acids (EAA), β-hydroxy β-methylbutyrate (HMB), creatine, dehydroepiandrosterone (DHEA) and fatty acid supplementation on muscle mass, muscle strength and physical performance of elderly subjects.
METHODS
Using the electronic databases MEDLINE and EMBASE we identified RCTs published until February 2016 which assessed the effects of these nutrient supplementation on muscle strength, muscle mass or physical performance. Study selection and data extraction were performed by two independent reviewers.
RESULTS
Search strategy allowed us to identify 23 RCTs. Among them, four used proteins as nutritional supplement, seven EAAs, six creatine, four DHEA and finally, two HMB. From our systematic review, it seems that the effects of these supplementations on muscle health are rather limited. Only consistent effects of EAA supplementation on physical performance (3 out of the 4 RCTs using EAA supplementation found significant effect of this supplementation on physical performance) and HMB supplementation on muscle mass (all the 2 identified RCTs using HMB supplementation found significant effect of this supplementation on muscle mass) have been found across studies. No consistent effects were found for the other types of dietary supplementation. Because of the important limitations in study design, inconsistency and lack of directness, the overall quality of the evidence was judged to be low or very low using the GRADE system.
CONCLUSION
This systematic review showed a limited effect of nutritional supplementation on muscle mass, muscle power and physical function. Inconsistent positive effects were observed for some specific supplementations but the results only concerned one aspect of the muscle. Well designed and appropriately powered RCTs are needed to provide evidence for appropriate clinical recommendations.
Topics: Aged; Aged, 80 and over; Amino Acids, Essential; Creatine; Dehydroepiandrosterone; Dietary Proteins; Dietary Supplements; Exercise; Fatty Acids; Female; Humans; Male; Middle Aged; Muscle Strength; Muscle, Skeletal; Physical Functional Performance; Resistance Training
PubMed: 29300431
DOI: 10.1007/s12603-017-0934-z