-
Frontiers in Endocrinology 2023Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in... (Meta-Analysis)
Meta-Analysis
Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models.
BACKGROUND
Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility.
MATERIAL AND METHODS
We systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen's d) and 95% confidence interval.
RESULTS
24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high-fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen's testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress.
CONCLUSIONS
Melatonin can reduce damage to male rodents' gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.
Topics: Animals; Male; Mice; Rats; Body Weight; Diabetes Mellitus; Hyperthyroidism; Infertility, Male; Melatonin; Metabolic Diseases; Obesity; Oxidative Stress; Rodentia; Semen; Testis
PubMed: 37476491
DOI: 10.3389/fendo.2023.1202560 -
European Journal of Obstetrics,... Nov 2022Placental insufficiency affects about 10% of pregnancies and can lead to pre-eclampsia, fetal growth restriction, and preterm birth. Despite significant advances in... (Review)
Review
Placental insufficiency affects about 10% of pregnancies and can lead to pre-eclampsia, fetal growth restriction, and preterm birth. Despite significant advances in early prediction and prevention of preterm pre-eclampsia with aspirin, the effects of prophylaxis on fetal growth restriction are less certain, and the rates of late-onset pre-eclampsia are not influenced by aspirin treatment. Pregnancies complicated by placental insufficiency are characterized by increased oxidative stress, and recent studies suggest that melatonin has antioxidant properties and contributes to maintaining placental homeostasis. We aimed to systematically review the available literature about melatonin in pregnancies complicated by placental insufficiency, specifically preeclampsia and fetal growth restriction, exploring three different aspects: 1) maternal melatonin levels; 2) expression and activity of melatonin placental receptors; 3) effects of maternal melatonin administration. PubMed (Medline) and Scopus were searched until December 2020. Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in qualitative evidence synthesis. The circadian pattern of melatonin secretion seems to be altered in pregnancies complicated by placental insufficiency reflected by lower production of melatonin, with consequent lower systemic and placental concentrations and lower expression of melatonin receptors, thus reducing the local release of the indole and its autocrine function. Small intervention studies also suggest that treatment is safe and may lead to prolongation of pregnancy and better outcomes, but double-blind, randomized placebo-controlled trials are lacking.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Placental Insufficiency; Pre-Eclampsia; Melatonin; Fetal Growth Retardation; Placenta; Antioxidants; Receptors, Melatonin; Premature Birth; Aspirin; Randomized Controlled Trials as Topic
PubMed: 36108451
DOI: 10.1016/j.ejogrb.2022.08.029 -
BMC Geriatrics Oct 2019Older surgical patients are at high risk of developing postoperative delirium. Non-pharmacological strategies are recommended for delirium prevention, but no... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Older surgical patients are at high risk of developing postoperative delirium. Non-pharmacological strategies are recommended for delirium prevention, but no pharmacological agents have compelling evidence to decrease the incidence of delirium. The purpose of this study was to assess whether perioperative melatonin decreases the incidence of delirium in older adults undergoing surgical procedures.
METHODS
A systematic search using PubMed/Medline, Embase, PsycINFO, CINAHL, and references of identified articles published in English between January 1990 and October 2017 was performed. Two independent reviewers screened titles and abstracts, and then extracted data following a full-text review of included articles with consensus generation and bias assessment. Studies reporting outcomes for melatonin or ramelteon use to prevent delirium in postoperative hospitalized patients (mean age ≥ 50 years) were eligible for inclusion. Data were pooled using a fixed-effects model to generate a forest plot and obtain a summary odds ratio for the outcome of interest (delirium incidence). Cochran's Q and I values were used to investigate heterogeneity.
RESULTS
Of 335 records screened, 6 studies were selected for the qualitative analysis and 6 were included in the meta-analysis (n = 1155). The mean age of patients in included studies ranged from 59 to 84 years. Patients in intervention groups typically received melatonin or ramelteon at daily doses of two to eight milligrams around cardiothoracic, orthopedic, or hepatic surgeries for one to nine days, starting on the evening before or the day of surgery. The incidence of delirium ranged from 0 to 30% in the intervention groups versus 4-33% in the comparator groups, and was significantly reduced in the melatonin group, with a summary effect of the meta-analysis yielding an odds ratio of 0.63 (95% CI 0.46 to 0.87; 0.006; I = 72.1%). A one study removed analysis reduced overall odds ratio to 0.310 (95% CI 0.19 to 0.50), while reducing heterogeneity (Cochran's Q = 0.798, I = 0.000).
CONCLUSION
Perioperative melatonin reduced the incidence of delirium in older adults in the included studies. While optimal dosing remains an unanswered question, the potential benefit of melatonin and melatonin receptor agonists may make them a reasonable option to use for delirium prevention in older adults undergoing surgical procedures.
Topics: Aged; Aged, 80 and over; Central Nervous System Depressants; Delirium; Humans; Incidence; Melatonin; Middle Aged; Postoperative Cognitive Complications; Randomized Controlled Trials as Topic
PubMed: 31619178
DOI: 10.1186/s12877-019-1297-6 -
Annals of Palliative Medicine May 2020Type 2 diabetes mellitus (T2DM) is associated with a large number of genetic variants of melatonin receptor 1B (MTNR1B), but the results of studies involving different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Type 2 diabetes mellitus (T2DM) is associated with a large number of genetic variants of melatonin receptor 1B (MTNR1B), but the results of studies involving different racial groups have been inconsistent. Thus, we carried out a meta-analysis to evaluate the correlation between the MTNR1B variants and T2DM in the Chinese population.
METHODS
A systematic search was conducted of English-language databases including PubMed, Embase, and Medline, and Chinese-language databases including China National Knowledge Infrastructure (CNKI), Wanfang Database, and CQVIP to collect relevant articles published up to January 31, 2020. Count data were pooled using odds ratio (OR) and 95% confidence interval (CI), and the analysis was performed using the "meta" package of the R3.5.1 software.
RESULTS
Nine articles involving 10,127 subjects in the T2DM group and 10,885 subjects in the healthy control group were entered into the final analysis. Four articles reported the rs1387153 variant of the MTNR1B gene in Chinese populations. Meta-analysis showed there to be no correlation between the C-allele and TT genotype and the occurrence of T2DM. However, a subgroup analysis based on the HardyWeinberg equilibrium (HWE) revealed that the frequency of the CC genotype was significantly lower in the T2DM group than in the control group (OR: 0.88; 95% CI: 0.78, 1.00; P=0.049). Seven articles reported the rs10830963 variant of the MTNR1B gene among Chinese populations. Meta-analysis discovered that the G-allele was correlated with the T2DM occurrence. The frequency of the G-allele in the T2DM group was 1.07 times that in the control group (95% CI: 1.02, 1.12). The GG genotype was associated with the occurrence of T2DM, with its frequency in the T2DM group 1.15 times that in the control group (95% CI: 1.05, 1.25) (P<0.05); however, there was no correlation between the CC genotype and T2DM.
CONCLUSIONS
There is a correlation between the CC genotype of the rs1387153 variant in the MTNR1B gene and T2DM in the Chinese population, although this finding needs to be verified in studies with large sample sizes. The G-allele and GG genotype of the rs10830963 variant in the MTNR1B gene are associated with the occurrence of T2DM.
Topics: China; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; Receptor, Melatonin, MT2
PubMed: 32434355
DOI: 10.21037/apm-20-691 -
Acta Psychiatrica Scandinavica Apr 2022The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT.
METHODS
Electronic databases of Pubmed, PsycInfo, Embase and Scopus were searched from inception through 1 April, 2021, using terms for ECT (e.g. electroconvulsive therapy), cognitive outcome (e.g. cogni*) and pharmacological intervention (e.g. calcium channel blocker and general terms, like protein). Original studies with humans receiving ECT were included, which applied pharmacological interventions in comparison with placebo or no additive intervention to diminish cognitive side effects. Data quality was assessed using Risk of Bias and GRADE. Random-effects models were used. PROSPERO registration number was CRD42021212773.
RESULTS
Qualitative synthesis (systematic review) showed 52 studies reporting sixteen pharmacological intervention-types. Quantitative synthesis (meta-analysis) included 26 studies (1387 patients) describing twelve pharmacological intervention-types. Low-quality evidence of efficacy was established for memantine (large effect size) and liothyronine (medium effect size). Very low-quality evidence shows effect of acetylcholine inhibitors, piracetam and melatonin in some cognitive domains. Evidence of no efficacy was revealed for ketamine (very low-quality), herbal preparations with anti-inflammatory properties (very low to low-quality) and opioid receptor agonists (low-quality).
CONCLUSION
Memantine and liothyronine are promising for further research and future application. Quality of evidence was low because of differences in ECT techniques, study populations and cognitive measurements. These findings provide a guide for rational choices of potential pharmacological intervention research targets to decrease the burden of cognitive side effects of ECT. Future research should be more uniform in design and attempt to clarify pathophysiological mechanisms of cognitive side effects of ECT.
Topics: Cognition; Electroconvulsive Therapy; Humans; Ketamine; Memantine; Triiodothyronine
PubMed: 35075641
DOI: 10.1111/acps.13397 -
Medicine Jan 2019Melatonin is the "clock factor" generated from pineal gland dominating regular circadian rhythm in humans. Migraine is one of the most severe and debilitating primary...
BACKGROUND
Melatonin is the "clock factor" generated from pineal gland dominating regular circadian rhythm in humans. Migraine is one of the most severe and debilitating primary headache disorders. Thus far, many diseases have been found to associate with melatonin, including the migraine. Therefore, melatonin's therapeutic potential for migraine is drawing attention.
OBJECTIVES
The aim of this study is to offer a systematic review of extant data of melatonin in migraine prophylaxis and to provide clinical implications and specific recommendations for future studies.
DATA SOURCES AND STUDY METHODS
A systematic research was conducted in September 2018 by using PubMed and Google Scholar databases to search for science literature published after 1988.
RESULTS
In all, 7 eligible articles were identified, including 4 randomized controlled studies and 3 observational studies. Due to high heterogeneities and limited number of studies, meta-analysis was not feasible, and only systematic review was performed. The results show that present evidence cannot claim melatonin's effectiveness according to the conflicting outcomes; however, the two negative outcomes of melatonin not different from placebo and melatonin inferior to amitriptyline are possible under-powering because of methodological, pharmacological, and therapeutic shortcomings. Observational studies also support melatonin's efficacy in migraine. As a result, melatonin is very likely to benefit migraine in prophylaxis and may have a similar effectiveness to other main preventive medications. Immediate-release melatonin 3 mg was established as effective, melatonin receptor agonist (Agomelatine) 25 mg and prolonged-release melatonin 4 mg were observed efficacious in observational studies. Melatonin displayed ineffective in the 2-month trial; thus, 3 months or more may be an enough duration for migraine therapy. Despite melatonin being generally safe, emerging literature is illustrating that a few severe adverse effects can be caused by melatonin, for example, liver injuries, reproductive system dysfunctions, and detrimental immunostimulation.
CONCLUSIONS
Melatonin is very likely to be a promising alternative for migraine prophylaxis. Current literature examining melatonin's efficacy in migraine prevention is growing, but still limited. Future studies of perfect design in methodology, pharmacology, and therapeutics are needed to achieve a deeper awareness of melatonin's role in migraine as well as more studies to explore the safety issues of melatonin medicine.
Topics: Central Nervous System Depressants; Humans; Melatonin; Migraine Disorders; Observational Studies as Topic; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Tension-Type Headache
PubMed: 30653130
DOI: 10.1097/MD.0000000000014099 -
Neuroscience and Biobehavioral Reviews Feb 2024Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural... (Review)
Review
BACKGROUND
Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural interventions (plant/endogenously-derived) to reduce treatment-related cognitive impairments.
METHODS
PubMed, EMBASE, PsycINFO, Web of Science, and Scopus were searched and SYRCLE's tool was used for risk of bias assessment of the 134 included articles.
RESULTS
High variability was observed and risk of bias analysis showed overall poor quality of reporting. Results generally showed positive effects in the intervention group versus cancer-therapy only group (67% of 156 cognitive measures), with only 15 (7%) measures reporting cognitive impairment despite intervention. Both artificial (61%) and natural (75%) interventions prevented cognitive impairment. Artificial interventions involving GSK3B inhibitors, PLX5622, and NMDA receptor antagonists, and natural interventions utilizing melatonin, curcumin, and N-acetylcysteine, showed most consistent outcomes.
CONCLUSIONS
Both artificial and natural interventions may prevent cognitive impairment in rodents, which merit consideration in future clinical trials. Greater consistency in design is needed to enhance the generalizability across studies, including timing of cognitive tests and description of treatments and interventions.
Topics: Humans; Animals; Cognitive Dysfunction; Cancer Survivors
PubMed: 38135266
DOI: 10.1016/j.neubiorev.2023.105514 -
Human Reproduction Update 2013Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were... (Review)
Review
BACKGROUND
Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies.
METHODS
Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity.
RESULTS
Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (-30G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P < 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P = 0.002) per T allele of rs12255372.
CONCLUSIONS
In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.
Topics: Alleles; Cyclin-Dependent Kinase 5; Diabetes, Gestational; Female; Humans; Insulin; Insulin Receptor Substrate Proteins; Insulin Secretion; Polymorphism, Single Nucleotide; Pregnancy; RNA-Binding Proteins; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Risk; Transcription Factor 7-Like 2 Protein; tRNA Methyltransferases
PubMed: 23690305
DOI: 10.1093/humupd/dmt013 -
Scientific Reports Jul 20176-Sulfatoxymelatonin (aMT6s) is the main metabolite of melatonin in urine, and is a reliable surrogate biomarker reflecting the blood melatonin concentration. This... (Meta-Analysis)
Meta-Analysis
6-Sulfatoxymelatonin (aMT6s) is the main metabolite of melatonin in urine, and is a reliable surrogate biomarker reflecting the blood melatonin concentration. This meta-analysis assessed the association between urinary aMT6s level and BC incidence. The electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science were searched. Risk ratios (RRs) were adopted to estimate the relative BC incidence. A total of 7 prospective case-control publications were included, and 6 of them were distinct studies. Pooled analysis of data from the 6 studies involving 1824 women with incident BC and 3954 matched control participants with no overlapping of subjects among studies indicated no significant association between the highest levels of urinary aMT6s and the incidence of BC (RR = 0.97, 95% CI, 0.88-1.08, P = 0.56). Negative associations were observed in postmenopausal women (RR = 0.88, 95% CI, 0.75-1.02, P = 0.10), estrogen receptor positive BC (RR = 0.83, 95% CI, 0.64-1.07, P = 0.15), and studies using 12-hour overnight urine (RR = 0.81, 95% CI, 0.61-1.07, P = 0.13), all with borderline significances. Lag time or invasive degree did not interfere with the results. There was no evident publication bias detected by the Egger's test and the funnel plot. Conclusively, the current evidence did not support a significant association between urinary aMT6s level and BC risk.
Topics: Breast Neoplasms; Humans; Incidence; Melatonin; Prospective Studies; Risk Assessment
PubMed: 28706222
DOI: 10.1038/s41598-017-05752-9 -
Revista Da Associacao Medica Brasileira... Sep 2019Melatonin is known for its effects on both the sleep and reproductive system of mammals. The latter has melatonin receptors type 1 and 2, which act to regulate, among...
Melatonin is known for its effects on both the sleep and reproductive system of mammals. The latter has melatonin receptors type 1 and 2, which act to regulate, among other things, cyclic AMP. Notwithstanding all the literature data, there is still no sound knowledge or a clear understanding of the hormone's action on the physiology of ovarian follicular cells. OBJECTIVE To review and evaluate studies about melatonin action on the ovarian granulosa/theca interna cells from the literature. METHODS The systematic review was carried out according to the PRISMA recommendations. The MEDLINE and Cochrane primary databases were consulted with the use of specific terms. There was no limitation on language or publication year. RESULTS Seven papers about melatonin action on granulosa cells were selected. The following can be attributed to the hormone's effects: a) progesterone increase in culture medium; b) increased estrogen production; c) antagonistic action on estrogen; d) improvement in cell quality resulting in improved embryo and higher pregnancy rates; e) improved cell proliferation via MAPK; f) reduction of free radicals. Nevertheless, there are contrarian papers reporting a reduction in progesterone production. Melatonin interferes in sex steroid production, boosting progesterone output. Such action may help improve oocyte quality.
Topics: Cells, Cultured; Female; Granulosa Cells; Humans; Melatonin; Oocytes; Ovarian Follicle; Pregnancy; Progesterone; Theca Cells
PubMed: 31531613
DOI: 10.1590/1806-9282.65.8.1122