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European Journal of Endocrinology Jan 2024Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism.
DESIGN
Systematic review and meta-analysis.
METHODS
A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713).
RESULTS
After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high.
CONCLUSIONS
This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.
Topics: Humans; Male; Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Hypogonadism; Klinefelter Syndrome; Spermatogenesis; Testis; Testosterone; Young Adult
PubMed: 38128110
DOI: 10.1093/ejendo/lvad166 -
Andrology Sep 2023Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men with obesity-related functional androgen deficiency.
OBJECTIVE
To determine whether and to what extent selective estrogen receptor modulators are an effective and safe therapy in men with obesity-related functional androgen deficiency.
MATERIALS AND METHODS
A thorough search of PubMed, Web of Science, Scopus, and Cochrane Library databases was performed to identify studies comparing testosterone levels before and after treatment. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias.
RESULTS
Seven studies met the inclusion criteria providing information on 292 men with obesity-related functional androgen deficiency treated with clomiphene citrate (12.5-50 mg daily) or enclomiphene citrate (12.5-25 mg daily) for 1.5-4 months. The pooled estimates indicated a significant increase in testosterone levels both with clomiphene (mean difference: 11.56 nmol/L; 95% coefficient interval: 9.68, 13.43; I = 69%, p = 0.01) and enclomiphene citrate (mean difference: 7.50 nmol/L; 95% coefficient interval: 6.52, 8.48; I = 4%, p = 0.37). After the exclusion of one study on severely obese men, who exhibited the highest response rate to clomiphene citrate, the heterogeneity disappeared (mean difference: 10.27 nmol/L; 95% coefficient interval: 9.39, 11.16; I = 0%, p = 0.66). No publication bias was revealed by Egger's test and trim-and-fill analysis. No treatment-related unexpected findings regarding safety profile were registered.
DISCUSSION AND CONCLUSION
Treatment with clomiphene citrate and enclomiphene citrate may be an effective and safe alternative to testosterone replacement therapy in men with obesity-related functional androgen deficiency. Further long-term studies are warranted to define clinical reflections of the selective estrogen receptor modulators-induced increase in testosterone levels and to better clarify the safety profile.
Topics: Humans; Male; Androgens; Clomiphene; Enclomiphene; Eunuchism; Hypogonadism; Obesity; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Testosterone
PubMed: 36604313
DOI: 10.1111/andr.13373 -
Critical Reviews in Oncology/hematology Jul 2018Paraoxonase-1 (PON1) is a lipolactonase implicated in the elimination of carcinogenic free radicals and in the scavenging mechanisms to maintain oxidative balance. The... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Paraoxonase-1 (PON1) is a lipolactonase implicated in the elimination of carcinogenic free radicals and in the scavenging mechanisms to maintain oxidative balance. The objective of the present systematic review and meta-analysis was to evaluate possible alterations in serum PON1 activity in patients with cancer.
METHODS
A systematic search of the observational studies in humans published in the last 15 years was performed through Medline databases following the PRISMA and STARLITE statements. Further, a keyword-based computerized search with restrictions on publication date, and a meta-analysis of case-control studies was performed.
RESULTS
In total, 23 studies were included most of which reported decreased PON1 activity in patients with cancer. This could indicate impaired defense ability against oxidative stress with potential implications in cell proliferation, promotion of genetic instability, and alterations in cellular sensitivity to chemotherapy.
CONCLUSION
This systematic review and meta-analysis confirms a consistent association between cancer and decreased serum PON1 activities. These findings may open fruitful lines of research with clinical relevance, and an understanding of molecular alterations underlying carcinogenesis.
Topics: Aryldialkylphosphatase; Case-Control Studies; Female; Humans; Male; Neoplasms; Oxidation-Reduction; Oxidative Stress
PubMed: 29891113
DOI: 10.1016/j.critrevonc.2018.04.005 -
Andrology Feb 2023Type 2 diabetes mellitus and pre-diabetes are associated with reduced circulating testosterone levels. However, the role of testosterone replacement therapy in these... (Review)
Review
BACKGROUND
Type 2 diabetes mellitus and pre-diabetes are associated with reduced circulating testosterone levels. However, the role of testosterone replacement therapy in these patients is still conflicting.
OBJECTIVES
To summarize and critically analyze available data on the possible effect of testosterone administration in men with glucose abnormalities.
MATERIALS AND METHODS
A comprehensive systematic review was performed. When available, meta-analytic data were preferred. To better analyze the relationship between testosterone and the pre-diabetes condition, a systematic analysis was performed and the data obtained with the latter search were used for a meta-analytic approach. Finally, clinical data derived from a consecutive series of 4682 patients seeking medical care for sexual dysfunction at the University of Florence were also considered.
RESULTS
Patients with impaired fasting glucose were characterized by a 3 nmol/L lower level of total testosterone when compared to controls. Similarly, impaired fasting glucose was associated with a 1.8-fold increased risk of hypogonadism, when compared to subjects with normal glucose levels. Waist circumference and body mass index resulted as being the best predictors of reduced total testosterone levels. Secondary hypogonadism was two times higher in subjects with impaired fasting glucose when compared to rates observed in the general population. Testosterone replacement therapy was able to improve body composition, insulin resistance, and glucose profile both in impaired fasting glucose and type 2 diabetes mellitus whereas its role on body weight, lipid profile, and sexual function was less evident.
DISCUSSION AND CONCLUSION
Weight loss and physical activities are able to improve both metabolic profile and testosterone levels. The combined approach of testosterone replacement therapy and lifestyle modifications could be suggested in symptomatic hypogonadal men to better motivate patients to perform physical activity which can eventually result in weight loss as well as metabolic profile and sexual function improvement. Whether or not these approaches can prevent the development of type 2 diabetes mellitus from pre-clinical conditions requires more studies.
Topics: Male; Humans; Testosterone; Diabetes Mellitus, Type 2; Prediabetic State; Hypogonadism; Weight Loss; Glucose; Hormone Replacement Therapy
PubMed: 36542412
DOI: 10.1111/andr.13367 -
Testosterone, DHEA and DHEA-S in patients with schizophrenia: A systematic review and meta-analysis.Psychoneuroendocrinology Mar 2018Neuroactive steroids, including testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) might play an important role in the pathophysiology of... (Meta-Analysis)
Meta-Analysis Review
Neuroactive steroids, including testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) might play an important role in the pathophysiology of schizophrenia. Therefore, we performed a systematic review and meta-analysis of studies comparing the levels of testosterone, DHEA and DHEA-S in patients with schizophrenia and healthy controls. We searched electronic databases from their inception until Oct 29, 2017. Effect size (ES) estimates were calculated as Hedges' g. Data analysis was performed using random-effects models. Our analysis included 34 eligible studies, representing 1742 patients and 1604 controls. Main analysis revealed elevated DHEA-S levels in the whole group of patients (ES = 0.75, 95%CI: 0.23-1.28, p = 0.005). In subgroup analyses, patients with first-episode psychosis (FEP) had significantly higher levels of free testosterone (ES = 1.21, 95%CI: 0.30-2.12, p = 0.009) and DHEA-S (ES = 1.19, 95%CI: 0.66-1.71, p < 0.001). Acutely relapsed schizophrenia patients presented significantly higher levels of total testosterone (ES = 0.50, 95%CI: 0.21-0.70, p < 0.001). Total testosterone levels were also elevated in stable multi-episode schizophrenia (sMES) females (ES = 0.56, 95%CI: 0.33-0.80, p < 0.001) and reduced in sMES males (ES = -0.62, 95%CI: -1.07 to 0.18, p = 0.006). Increased levels of biologically active, free testosterone and DHEA-S in FEP suggest that these alterations might appear as a response to stress that becomes blunted during subsequent exacerbations of schizophrenia. Differential changes in total testosterone levels in male and female sMES patients might represent medication effects related to prolactin-releasing effects of antipsychotics.
Topics: Adult; Antipsychotic Agents; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Male; Middle Aged; Schizophrenia; Testosterone
PubMed: 29334627
DOI: 10.1016/j.psyneuen.2018.01.007 -
Journal of Genetics and Genomics = Yi... Mar 2024Protein post-translational modifications (PTMs), such as ubiquitination, phosphorylation, and small ubiquitin-like modifier (SUMO)ylation, are crucial for regulating...
Protein post-translational modifications (PTMs), such as ubiquitination, phosphorylation, and small ubiquitin-like modifier (SUMO)ylation, are crucial for regulating protein stability, activity, subcellular localization, and binding with cofactors. Such modifications remarkably increase the variety and complexity of proteomes, which are essential for regulating numerous cellular and physiological processes. The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development. Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations. Thus, a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes. This review discusses the progress of protein ubiquitination, phosphorylation, histone acetylation and methylation, SUMOylation, and S-nitrosylation in the regulation of auxin signaling.
Topics: Indoleacetic Acids; Protein Processing, Post-Translational; Signal Transduction; Sumoylation; Ubiquitination
PubMed: 37451336
DOI: 10.1016/j.jgg.2023.07.002 -
Endocrine Practice : Official Journal... Sep 2023Age-related declines in muscle and bone, alongside a shift toward greater adiposity, contribute to falls and fracture risk. Testosterone is osteogenic, myogenic, and... (Meta-Analysis)
Meta-Analysis Review
Safety and Efficacy of Testosterone Therapy on Musculoskeletal Health and Clinical Outcomes in Men: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.
OBJECTIVE
Age-related declines in muscle and bone, alongside a shift toward greater adiposity, contribute to falls and fracture risk. Testosterone is osteogenic, myogenic, and catabolic to fat. As such, we examined the effects of testosterone therapy on musculoskeletal health and clinical outcomes in men.
METHODS
Electronic databases (Medline, Embase, Web of Science, Central) were systematically searched for randomized controlled trials (RCTs) reporting on the effects of testosterone therapy versus placebo on any primary outcome (bone density, muscle mass, fat mass, muscle strength/physical performance) or secondary outcome (falls, fractures, disability, adverse events) in men (≥18 years). A random effects meta-regression examined the effects of testosterone on prespecified outcomes.
RESULTS
One thousand seven hundred twenty-eight men across 16 RCTs were included (mean age: 77.1 ± 7.6 years). Baseline mean serum testosterone ranged from 7.5 ± 0.3 to 18.9 ± 1.2 nmol/L. Compared to placebo, 6 months of testosterone therapy increased hip bone density and total lean mass, but effects for handgrip and total fat mass did not reach statistical significance. No significant effects of testosterone therapy on musculoskeletal outcomes were evident at 12 months. The limited number of RCTs reporting on adverse events/clinical outcomes, and the low incidence of these events across RCTs, prohibited statistical comparisons.
CONCLUSION
After 6 months, testosterone effectively increases hip bone density and total lean mass in men, but its effects are unclear for lumbar spine bone density and handgrip strength. Further, RCTs are needed to clarify the safety and efficacy of testosterone on musculoskeletal health and clinical outcomes.
Topics: Male; Humans; Aged; Aged, 80 and over; Testosterone; Bone Density; Fractures, Bone; Bone and Bones; Muscle Strength; Randomized Controlled Trials as Topic
PubMed: 37164187
DOI: 10.1016/j.eprac.2023.04.013 -
Best Practice & Research. Clinical... Aug 2013Late-onset hypogonadism (LOH) is a relatively common conditions affecting the aging male. The aim of this review is to summarize the available evidence regarding LOH and... (Meta-Analysis)
Meta-Analysis Review
Late-onset hypogonadism (LOH) is a relatively common conditions affecting the aging male. The aim of this review is to summarize the available evidence regarding LOH and its interaction with general health. LOH is often comorbid to obesity and several chronic diseases. For this reason lifestyle modifications should be strongly encouraged in LOH subjects with obesity, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) and good treatment balance of chronic diseases. Medical therapy of LOH should be individualized depending on the etiology of the disease and the patient's expectations. Available evidence seems to suggest that testosterone replacement therapy is able to improve central obesity (subjects with MetS) and glycometabolic control (patients with MetS and T2DM), as well as to increase lean body mass (HIV, chronic obstructive pulmonary disease), along with insulin resistance (MetS) and peripheral oxygenation (chronic kidney diseases). However, it should be recognized that the number of studies on benefits of T supplementation is too limited to draw final conclusions. Longer and larger studies are needed to better clarify the role of TRT in such chronic conditions.
Topics: Aging; Diabetes Mellitus, Type 2; Hormone Replacement Therapy; Humans; Hypogonadism; Life Style; Male; Metabolic Syndrome; Obesity; Puberty; Testosterone; Treatment Outcome; Weight Loss
PubMed: 24054931
DOI: 10.1016/j.beem.2013.05.002 -
The Journal of Nutrition Jul 2021There is much debate regarding the source/quality of dietary proteins in supporting indices of skeletal muscle anabolism. (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is much debate regarding the source/quality of dietary proteins in supporting indices of skeletal muscle anabolism.
OBJECTIVE
We performed a systematic review and meta-analysis to determine the effect of protein source/quality on acute muscle protein synthesis (MPS) and changes in lean body mass (LBM) and strength, when combined with resistance exercise (RE).
METHODS
A systematic search of the literature was conducted to identify studies that compared the effects of ≥2 dose-matched, predominantly isolated protein sources of varying "quality." Three separate models were employed as follows: 1) protein feeding alone on MPS, 2) protein feeding combined with a bout of RE on MPS, and 3) protein feeding combined with longer-term resistance exercise training (RET) on LBM and strength. Further subgroup analyses were performed to compare the effects of protein source/quality between young and older adults. A total of 27 studies in young (18-35 y) and older (≥60 y) adults were included.
RESULTS
Analysis revealed an effect favoring higher-quality protein for postprandial MPS at rest [mean difference (MD): 0.014%/h; 95% CI: 0.006, 0.021; P < 0.001] and following RE (MD: 0.022%/h; 95% CI: 0.014, 0.030; P < 0.00001) in young (model 1: 0.016%/h; 95% CI: -0.004, 0.036; P = 0.12; model 2: 0.030%/h; 95% CI: 0.015, 0.045; P < 0.0001) and older (model 1: 0.012%/h; 95% CI: 0.006, 0.018; P < 0.001; model 2: 0.014%/h; 95% CI: 0.007, 0.021; P < 0.001) adults. However, although higher protein quality was associated with superior strength gains with RET [standardized mean difference (SMD): 0.24 kg; 95% CI: 0.02, 0.45; P = 0.03)], no effect was observed on changes to LBM (SMD: 0.05 kg; 95% CI: -0.16, 0.25; P = 0.65).
CONCLUSIONS
The current review suggests that protein quality may provide a small but significant impact on indices of muscle protein anabolism in young and older adults. However, further research is warranted to elucidate the importance of protein source/quality on musculoskeletal aging, particularly in situations of low protein intake.
Topics: Aged; Body Composition; Dietary Proteins; Humans; Muscle Strength; Muscle, Skeletal; Resistance Training
PubMed: 33851213
DOI: 10.1093/jn/nxab055 -
International Braz J Urol : Official... 2024Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones.
MATERIALS AND METHODS
Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool.
RESULTS
There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001).In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal.
CONCLUSION
Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.
Topics: Humans; Male; Databases, Factual; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Reference Values; Testosterone
PubMed: 38386784
DOI: 10.1590/S1677-5538.IBJU.2023.0578