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Effects of Different Therapeutic Exercise Modalities on Migraine or Tension-Type Headache: A Systematic Review and Meta-Analysis with a Replicability Analysis.
Varangot-Reille, C, Suso-Martí, L, Romero-Palau, M, Suárez-Pastor, P, Cuenca-Martínez, F
The journal of pain. 2022;23(7):1099-1122
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For individuals who suffer from headaches and migraines, the first treatment option is usually drug based, which has been associated with side effects, dependency, and abuse of medications. Exercise may be of benefit to individuals with headache and migraine, as it can stimulate the release of chemicals in the brain, which are beneficial to coping with pain. The aim of this systematic review and meta-analysis was to determine the effect of exercise in comparison to non-active treatment for pain, frequency of headache episodes, headache duration, quality of life and medication use in individuals with migraine or tension headache. The results showed that both aerobic and strength training were of benefit to the intensity of pain, which resulted in a decrease in medication use. Strength training was marginally better for pain than aerobic exercise, however the research that this was based on was of low quality. It was concluded that exercise could be considered a treatment option for those with migraine and headaches, however the evidence that this was based on was of low quality and so more research is needed before clinical recommendations could be made. This study could be used by healthcare professionals to understand that there may be some benefit of exercise for the management of pain in individuals who have migraines and headaches.
Abstract
The primary aim of this study was to review the effect of exercise in comparison with a non-active treatment on pain intensity, frequency of headache episodes, headache duration, quality of life, medication use, and psychological symptoms, in patients with migraine or tension-type headache (TTH). A systematic search was conducted in various electronic databases to identify all relevant studies: Medline (PubMed), PEDro, EBSCO and Google Scholar. Clinical trials assessing the effects of exercise interventions in patients with primary headaches were selected. Methodological quality was evaluated using the Cochrane Risk of Bias Tool and PEDro scale and qualitative analysis was based on classifying the results into levels of evidence according to the GRADE. 19 studies (2776 participants; 85% female) were included. The meta-analysis showed statistically significant differences in pain intensity for aerobic training in patients with migraine (SMD = -0.65; 95% CI = -1.07 to -0.22, very low certainty evidence) and for strength training in patients with TTH (SMD = -0.84; 95% CI = -1.68 to- -0.01, very low certainty evidence). Statistically significant differences were also found in the medication use (SMD = -0.51; 95% CI = -0.85 to -0.17, low certainty evidence). Low transparency, replicability and high risk of bias were found. Aerobic training has a small to moderate clinical effect on pain intensity and medication use on migraine patients, with very low to low certainty of evidence. Strength training showed a moderate clinical effect with very low quality of evidence in patients with TTH. Exercise could be considered as clinically relevant for the management of patients with primary headaches, but the presence of low certainty of evidence and low transparency and replicability limited its clinical application. PERSPECTIVE This article presents current evidence about exercise interventions in patients with primary headaches, including migraine and tension-type headache. Existing findings are reviewed, and relevant data are provided on the effectiveness of each exercise modality, as well as its certainty of evidence and clinical applicability.
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Effectiveness of Therapeutic Patient Education Interventions in Obesity and Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Correia, JC, Waqas, A, Huat, TS, Gariani, K, Jornayvaz, FR, Golay, A, Pataky, Z
Nutrients. 2022;14(18)
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Obesity and diabetes mellitus (DM) account for the highest burden of non-communicable diseases. Obesity is also highly comorbid with type 2 DM with a prevalence of 8.5% among adults around the globe. The aims of this study were to present (a) a critical synthesis of the theoretical basis and development of therapeutic patient education (TPE) interventions for obesity and diabetes, and (b) quantitative evidence for the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. This study is a systematic review and meta-analysis of fifty-four randomised controlled trials. Results show that: - TPE interventions bring about significant improvements in biomedical outcomes among patients with DM and obesity. - there weren’t significant differences in the quality of life of participants undergoing TPE interventions (inconclusive as only data from two studies were considered). - interventions delivered through different media and delivery formats may be equally effective. Authors conclude that the use of electronic media such as short messaging services, website-based educational programs and animation media can be used to deliver TPE effectively.
Abstract
Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis present a critical synthesis of the development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus qualitatively synthesized. Out of these, 47 were included in the quantitative synthesis. There was substantial heterogeneity in the reporting of these outcomes (I2 = 88.35%, Q = 317.64), with a significant improvement noted in serum HbA1c levels (standardized mean difference (SMD) = 0.272, 95% CI: 0.118 to 0.525, n = 7360) and body weight (SMD = 0.526, 95% CI: 0.205 to 0.846, n = 1082) in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (p < 0.001). These interventions should be implemented in healthcare and community settings to improve the health outcomes in patients suffering from obesity and DM.
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White rice, brown rice and the risk of type 2 diabetes: a systematic review and meta-analysis.
Yu, J, Balaji, B, Tinajero, M, Jarvis, S, Khan, T, Vasudevan, S, Ranawana, V, Poobalan, A, Bhupathiraju, S, Sun, Q, et al
BMJ open. 2022;12(9):e065426
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The prevalence of type 2 diabetes (T2D) has continued to increase worldwide, especially in low-income and middle-income countries. Since rice is a staple food in many cultures and is predominant in most Asian diets, it is hypothesised that improving diet quality by replacing white rice with brown rice could play an important role in the prevention of T2D. The aim of this study was to assess the relationship between rice intake and the risk of T2D. This study is a systematic review and meta-analysis of nineteen studies – 8 cohort studies and 11 randomised controlled trials. Results from the meta-analyses of the cohort studies show a positive association between intake of white rice and risk of T2D. The associations were stronger in women compared with men. Additionally, brown rice was inversely associated with risk of T2D however, the results are based on limited data. Furthermore, the randomised controlled trials showed that the between-group difference in high-density lipoprotein cholesterol was statistically significant in favour of the brown rice group. Authors conclude that replacing white rice with brown rice or other whole grains has the potential to be a low-cost and feasible lifestyle strategy to improve diet quality and help reduce T2D risk.
Abstract
OBJECTIVE Intake of white rice has been associated with elevated risk for type 2 diabetes (T2D), while studies on brown rice are conflicting. To inform dietary guidance, we synthesised the evidence on white rice and brown rice with T2D risk. DESIGN Systematic review and meta-analysis. DATA SOURCES PubMed, EMBASE and Cochrane databases were searched through November 2021. ELIGIBILITY CRITERIA Prospective cohort studies of white and brown rice intake on T2D risk (≥1 year), and randomised controlled trials (RCTs) comparing brown rice with white rice on cardiometabolic risk factors (≥2 weeks). DATA EXTRACTION AND SYNTHESIS Data were extracted by the primary reviewer and two additional reviewers. Meta-analyses were conducted using random-effects models and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the Newcastle Ottawa Scale for prospective cohort studies and the Cochrane Risk of Bias Tool for RCTs. Strength of the meta-evidence was assessed using NutriGrade. RESULTS Nineteen articles were included: 8 cohort studies providing 18 estimates (white rice: 15 estimates, 25 956 cases, n=5 77 426; brown rice: 3 estimates, 10 507 cases, n=1 97 228) and 11 RCTs (n=1034). In cohort studies, white rice was associated with higher risk of T2D (pooled RR, 1.16; 95% CI: 1.02 to 1.32) comparing extreme categories. At intakes above ~300 g/day, a dose-response was observed (each 158 g/day serving was associated with 13% (11%-15%) higher risk of T2D). Intake of brown rice was associated with lower risk of T2D (pooled RR, 0.89; 95% CI: 0.81 to 0.97) comparing extreme categories. Each 50 g/day serving of brown rice was associated with 13% (6%-20%) lower risk of T2D. Cohort studies were considered to be of good or fair quality. RCTs showed an increase in high-density lipoprotein-cholesterol (0.06 mmol/L; 0.00 to 0.11 mmol/L) in the brown compared with white rice group. No other significant differences in risk factors were observed. The majority of RCTs were found to have some concern for risk of bias. Overall strength of the meta-evidence was moderate for cohort studies and moderate and low for RCTs. CONCLUSION Intake of white rice was associated with higher risk of T2D, while intake of brown rice was associated with lower risk. Findings from substitution trials on cardiometabolic risk factors were inconsistent. PROSPERO REGISTRATION NUMBER CRD42020158466.
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Effects of camelina oil supplementation on lipid profile and glycemic control: a systematic review and dose‒response meta-analysis of randomized clinical trials.
Jalili, C, Talebi, S, Mehrabani, S, Bagheri, R, Wong, A, Amirian, P, Zarpoosh, M, Ghoreishy, SM, Kermani, MAH, Moradi, S
Lipids in health and disease. 2022;21(1):132
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Research indicates that alpha-linolenic acid (ALA) can reduce the risk of cardiovascular disease by improving blood lipids, blood pressure, and haemostatic factors, among others. Camelina oil, considered a good source of ALA compared to other edible oils, is one of the richest dietary sources of omega-3 fatty acids, with a polyunsaturated fatty acid content over 50%. The aim of this study was to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycaemic control in human studies. This study is a systematic review and meta-analysis of seven randomised controlled trials with a total of 428 individuals (202 participants in the COS group and 226 in the control group). Results did not show any affects of COS on lipid profile and glycaemic indices compared with placebo intake. However, subgroup analysis showed that COS for more than 8 weeks and at a dose lower than 30g/d could decrease total cholesterol. Authors conclude that COS may be a beneficial nonpharmacological strategy for the improvement of this lipid marker. However, further studies are required to confirm the findings of this study.
Abstract
BACKGROUND This systematic review and dose-response meta-analysis of published randomized controlled trials (RCTs) was conducted to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycemic indices. METHODS Relevant RCTs were selected by searching the ISI Web of Science, PubMed, and Scopus databases up to July 1, 2022. RTCs with an intervention duration of less than 2 weeks, without a placebo group, and those that used COS in combination with another supplement were excluded. Weighted mean differences and 95% confidence intervals were pooled by applying a random-effects model, while validated methods examined sensitivity analyses, heterogeneity, and publication bias. RESULTS Seven eligible RCTs, including 428 individuals, were selected. The pooled analysis revealed that COS significantly improved total cholesterol in studies lasting more than 8 weeks and utilizing dosages lower than 30 g/d compared to the placebo group. The results of fractional polynomial modeling indicated that there were nonlinear dose-response relations between the dose of COS and absolute mean differences in low-density cholesterol, high-density cholesterol, and total cholesterol, but not triglycerides. It appears that the greatest effect of COS oil occurs at the dosage of 20 g/day. CONCLUSION The present meta-analysis indicates that COS may reduce cardiovascular disease risk by improving lipid profile markers. Based on the results of this study, COS at dosages lower than 30 g/d may be a beneficial nonpharmacological strategy for lipid control. Further RCTs with longer COS durations are warranted to expand on these results.
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Effects of lifestyle interventions on cardiovascular risk factors in South Asians: a systematic review and meta-analysis.
Limbachia, J, Ajmeri, M, Keating, BJ, de Souza, RJ, Anand, SS
BMJ open. 2022;12(12):e059666
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The prevalence of cardiovascular disease (CVD) and associated mortality risk is high in the South Asian population in western countries. Regular physical activity and a healthy diet may modify the risk factors of CVD, such as abdominal fat, high cholesterol, and blood sugar irregularities. This systematic review and meta-analysis included thirty-five randomised controlled trials to evaluate the effectiveness of diet, physical activity interventions or a combination of diet and physical activity interventions on CVD risk factors and compared it against usual care. Combining diet and physical activity interventions reduced CVD risk factors such as systolic and diastolic blood pressure, BMI, weight, waist circumference and fasting plasma glucose (FPG). Dietary interventions reduced diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, BMI, weight and FPG. Physical activity modifications improved diastolic and systolic blood pressure and high-density lipoprotein cholesterol. Healthcare professionals can use the study results to understand how tailored diet and physical activity modifications improve the CVD risk factors in South Asians. However, further robust studies are required as most of these evidences were of moderate quality and lacked clinical significance.
Abstract
BACKGROUND The cardiovascular disease (CVD) burden among South Asians is high. Lifestyle interventions have been effective in the primary prevention of CVD, but this has not been replicated, through a synthesis of randomised trials, in South Asians. METHODS Four electronic databases (MEDLINE, Embase, CENTRAL and CINAHL), two clinical trial registries and references of included articles were searched through June 2022 (featuring ≥90% South Asian participants). Random-effects pairwise meta-analyses were performed, and heterogeneity was quantified with the I2 statistic. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to report on the quality of evidence (International Prospective Register of Systematic Reviews registration (PROSPERO). RESULTS Thirty-five studies were included. Twelve tested diet and physical activity interventions; 18 tested diet alone; and 5 tested physical activity alone. All reported effects of the intervention(s) on at least one established risk factor for CVD, including blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids (high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) or triglycerides). No trials reported clinical CVD. There is moderate-quality evidence that diet and physical activity interventions improve SBP (mean difference (MD) -2.72 mm Hg, 95% CI -4.11 to -1.33) and DBP (MD -1.53 mm Hg, 95% CI -2.57 to -0.48); high-quality to moderate-quality evidence that diet-only interventions improve DBP (MD -2.05 mm Hg, 95% CI -2.93 to -1.16) and blood lipids (triglycerides (MD -0.10 mmol/L, 95% CI -0.14 to -0.06) and LDLc (MD -0.19 mmol/L, 95% CI -0.32 to -0.06)); and moderate-quality evidence that physical activity-only interventions improve SBP (MD -9.7 mm Hg, 95% CI -11.05 to -8.35), DBP (MD -7.29 mm Hg, 95% CI -8.42 to -6.16) and HDLc (MD 0.08 mmol/L, 95% CI 0.04 to 0.11) compared with usual care. CONCLUSIONS Lifestyle interventions improve blood pressure and blood lipid profiles in adult South Asians at risk of CVD. Tailored interventions should be used to modify cardiovascular risk factors in this at-risk group. PROSPERO REGISTRATION NUMBER CRD42018090419.
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Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.
Whittaker, J, Harris, M
Nutrition and health. 2022;28(4):543-554
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Testosterone is the primary male sex hormone, and vital for reproductive development and function. Moreover, low endogenous testosterone is associated with an increased risk of chronic disease, including type 2 diabetes and cardiovascular disease. The aim of this study was to investigate the effects of low- versus high-carbohydrate diets on mens' testosterone and cortisol. This study is a systematic review and meta-analysis of twenty-seven studies with a total of 309 participants. Twelve of these studies were randomised trials whilst the rest were non-randomised. Results show an increase in resting and post-exercise cortisol on short-term low-carbohydrate diets (<3 weeks). In fact, resting cortisol levels return to baseline after <3 weeks on a LC diet, whilst post-exercise cortisol remains elevated. Furthermore, high-protein diets cause a large decrease in resting total testosterone. Authors conclude that further research is required in order to warrant their findings.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short-term LC-diets diets cause a moderate increase in resting and post-exercise cortisol however this effect is not seen in LC-diets followed for great than 3 weeks
- HP-LC diets caused a statistically significant decrease in resting TT, suggesting caution in relation to endocrine effects of LC diets
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction:
A systematic review and network meta-analysis was conducted on the effects of low-carbohydrate (LC) versus high-carbohydrate (HC) diets on men’s testosterone and cortisol.
The review was registered with PROSPERO and reported using PRISMA 2020 checklists.
Methods:
A comprehensive search strategy was used to find intervention studies looking at healthy adult males and LC diets of <35% carbohydrate. Studies were assessed for quality using the Cochrane Risk of Bias tool. Sub-group analyses was conducted for diet duration, protein intake and exercise duration.
Results:
The literature search resulted in 27 studies with a total of 309 healthy adult male participants, age: 27.3 ± 4.7 (to minimise variation in steroid hormone metabolism), body mass: 78.6± 7.1kg and BMI: 24.8 ±1.6. 12 randomised and 15 non-randomised controlled trials were analysed. 21 studies were considered low risk bias, 5 medium and 1 high risk.
- Short-term (<3 weeks) LC diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01) when compared to HC diets.
- Long-term (≥3 weeks) LC diets had no consistent effect on resting cortisol
- LC diets resulted in higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01).
- The overall results for resting total testosterone (TT) showed a significant decrease on LC versus HC diets (SMD = −0.48, p = 0.01. However, subgroup analyses revealed this effect to be limited to high-protein (HP) LC diets, which yielded a very large decrease in TT (SMD = −1.08, p < 0.01; ∼5.23 nmol/L), albeit in a small sample (n = 26).
- Moderate protein (MP) (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05).
- There was no overall effect of LC versus HC diets on 0 h post-exercise TT (SMD = −0.03, p = 0.95). However, subgroup analysis showed 0 h post-exercise was non-significantly higher on long-term LC versus HC diets (SMD = 0.44, p = 0.18), and much lower on short-term LC versus HC diets (SMD = −1.01, p = 0.05)
Conclusion:
This systematic review and metanalysis found an increase in resting and post-exercise cortisol on short-term LC diets. Cortisol does return to baseline in the first 3 weeks of a low-carbohydrate (LC) diet. The same response is, however, not seen in post-exercise cortisol, which remains elevated. In addition, the review showed that compared to moderate-protein diets, HP diets were found to cause a large decrease in resting and post-exercise TT (∼5.23 nmol/L).
Clinical practice applications:
The results of this review suggest that exercising whilst following a LC diet can increase cortisol in the short term, but not long-term. This suggests a period of diet adaptation. The effects of long-term LC diets on cardiovascular disease risk is uncertain and healthcare practitioners should monitor client responses and keep up-to-date with new research in this area
Since HP-LC diets were found to significantly decrease resting testosterone it highlights the need to ensure that protein intake does not exceed the urea cycle’s capacity due to potential adverse endocrine effects.
For clients where there is a desire to increase strength, power and hypertrophy, a MP-LC diet could be of benefit, as it showed potential to signal an increased anabolic state post exercise..
NB: Since the review only included a low number of studies and saw within these some heterogeneity that could not be explained, more research is needed before the paper’s findings can be conclusive. The above potential practice applications should therefore be seen as something to be mindful of when working with clients where cortisol and testosterone levels are relevant to their protocol.
Considerations for future research:
Future research should consider:
- Since LC diets have been shown to have a positive effect on health – decreased triglycerides, increased high density lipoprotein cholesterol and weight loss - future studies would benefit from including these markers so any positive and negative impacts can be monitored directly.
- Despite extensive analysis including sensitivity analysis to reduce bias and heterogeneity of the results, the paper highlights a need for further research to ensure consistency in key parameters e.g., exercise duration and intensity, carbohydrate supplements inclusion and period of dietary intervention. Since it was identified that HP-LP diets impact post exercise and resting TT, follow up studies would benefit from consistency in participants diets. This would help to reduce any potential confounding results.
Abstract
Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (-1.08 [-1.67, -0.48], p < 0.01) and post-exercise total testosterone (-1.01 [-2, -0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
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Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.
Hudson, J, Cruickshank, M, Quinton, R, Aucott, L, Aceves-Martins, M, Gillies, K, Bhasin, S, Snyder, PJ, Ellenberg, SS, Grossmann, M, et al
The lancet. Healthy longevity. 2022;3(6):e381-e393
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Hypogonadism is caused by testosterone deficiency and results in diminished sexual function, muscle wastage, weakness, osteoporosis, and reduced quality of life. Testosterone supplementation is used as a therapy for hypogonadism but there is some doubt on its safety, and it may come with serious side effects such as heart attacks. This systematic review and meta-analysis aimed to determine the effect of testosterone supplementation on heart health. The results showed that heart disease risk was unaffected by testosterone supplementation and there was a trend for fewer deaths following treatment. It was concluded that testosterone did not affect short-medium-term heart attack risk, however there was a lack of evidence in the long-term. This study could be used by healthcare professionals to understand that testosterone supplementation may be of benefit to individuals who need it without increasing their risk for heart attacks.
Abstract
BACKGROUND Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. METHODS We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. FINDINGS 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. INTERPRETATION We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. FUNDING National Institute for Health Research Health Technology Assessment Programme.
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Systematic review and meta-analysis of candidate gene association studies of benign prostate hyperplasia.
Lin, L, Li, P, Liu, X, Xie, X, Liu, L, Singh, AK, Singh, HN
Systematic reviews. 2022;11(1):60
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Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate which can cause urinary dysfunction and may affect the quality of life of patients. Polymorphism in several genes has been linked to the high susceptibility of BPH. The aim of this study was to analyse genetic variations in important genes towards the susceptibility of BPH. This study is a systematic review and meta-analysis of twenty-three case-control studies (11 for CYP17 [gene], 10 for VDR - vitamin D receptor [a member of the steroid/ thyroid hormone receptor family] and 4 for ACE - angiotensin-converting enzyme [component of the renin–angiotensin system] polymorphisms). The sample size in each study ranged from 20 to 588 participants. Results show that genetic polymorphism in the ACE gene was significantly associated with the risk of BPH when compared with control subjects. Whereas there was a negative association for the polymorphism located in VDR and CYP17 genes with the risk of BPH. Authors conclude that larger studies with prospective data and larger sample sizes are required.
Abstract
BACKGROUND Benign prostate hyperplasia (BPH) is the most common urological problem in elderly males. Recent studies have reported polymorphism in various metabolic genes in BPH. However, their association with the susceptibility of BPH is still inconsistent. Here, we systematically reviewed and performed a meta-analysis of CYP17, VDR, and ACE genes to determine their precise association with the risk of BPH. METHODS A comprehensive literature search for published studies on candidate gene associations involving vitamin D receptor (VDR), angiotensin-converting enzyme (ACE), and CYP17 genes with the risk of BPH was done up to April 2020 in PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. Fixed/random effects models were used to estimate the odd's ratio (OR) and 95% confidence intervals (CIs). Begg's funnel plot was used to assess the potential for publication bias. RESULTS We found a total of 23 studies containing 3461 cases and 3833 controls for these gene polymorphisms. A significant association of ACE gene polymorphism was observed under the recessive (II vs. ID + DD) model for BPH susceptibility compared to control subjects (overall OR = 1.67, 95% CI = 1.03-2.73). Similar trends were observed for ACE gene polymorphism in Caucasian (OR = 6.18, 95% CI = 1.38-27.68) and Asian (OR = 1.42, 95% CI = 0.99-2.03) populations under study. No significant association was observed in VDR and CYP17 gene polymorphisms in any dominant or recessive models. CONCLUSION Significant OR demonstrated the implication of ACE gene polymorphism in the proliferation of prostate tissue, which in turn is associated with BPH susceptibility. However, prospective studies at large scale and sample size are needed to confirm the current findings.
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Effectiveness of Exercise Training on Male Factor Infertility: A Systematic Review and Network Meta-analysis.
Hajizadeh Maleki, B, Tartibian, B, Chehrazi, M
Sports health. 2022;14(4):508-517
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Plain language summary
Male factor infertility is characterised by the existence of suboptimal sperm parameters in the male partner of childbearing age and is presently defined as the inability to conceive a child with frequent and unprotected sexual intercourse in the fertile phase of the menstrual cycles for a year or longer. The main aim of this study was to evaluate the effectiveness of 1 or more of the selected types of exercise interventions (moderate-intensity continuous training (MICT), resistance training (RT), combined aerobic and resistance training (CET), high-intensity continuous training (HICT), and high-intensity interval training (HIIT)) in the prevention and treatment of male factor infertility. This study is a systematic review and meta-analysis of seven randomised controlled trials representing 18 groups (11 exercise, 7 non-intervention control [NON-EX]) and 2641 participants and/or patients (1429 exercise, 1212 NON-EX). Results show that in the setting of couples with male factor infertility, when compared with the NON-EX group, selected types of exercise interventions improved the relative risk of pregnancy rate in the following order: CET > MICT > RT > HICT > HIIT. The top-ranking interventions for live birth rate were for MICT, RT, HIIT, CET, and HICT. In addition, the interventions with the highest probability of being the best approach out of all available options in improving semen quality parameters were for CET, MICT, HICT, RT, and HIIT. Authors conclude that when clinicians are formulating clinical recommendations for preventing and treating male factor infertility, the findings of this study should be considered.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For couples with male factor infertility, this review recommends moderate intensity-aerobic exercise in combination with strength training to be the intervention with the highest probability of being the best approach for reproductive health benefits.
- A conservative interpretation of the findings is required because they were based on single studies.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
The World Health Organisation estimates that infertility affects 10% to 15% of couples in industrialised countries. Approximately 50% of all infertility cases are attributed to male-related factors, in particular, poor semen quality (called male factor infertility). The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation.
Methods
This is the first study to undertake a systematic review with network meta-analysis of 7 RCTs to evaluate the effectiveness of 1 or more types of exercise interventions on male factor infertility and seminal markers of inflammation, as well as to provide clinicians with a ranking of treatments to inform them of the treatment effects of exercise training and physical activity.
The forms of exercise include: moderate-intensity continuous training (MICT), resistance training (RT), combined aerobic and resistance training (CET), high-intensity continuous training (HICT), and high-intensity interval training (HIIT).
7 RCTs representing 18 groups (11 exercise (supervised, not home-based), 7 non-intervention control [NON-EX]) and 2641 participants and/or patients (1429 exercise, 1212 NON-EX). All the RCTs were conducted in Iran involving healthy adult participants and/or infertile patients (with doctor-diagnosed male factor infertility). The intervention period was ≥10 weeks with a follow-up period.
None of the studies reported changes in either patients’ dietary intakes or normal daily physical activities and lifestyles during the intervention period.
Results
Compared with a non-intervention control group, the top ranking interventions:
For pregnancy rate:
Combined aerobic and resistance training (CET) (p= 0.89 relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (p=0.87, RR = 26.67), resistance training (RT) (p=0.61,RR = 12.54), high intensity continuous training (HICT) (p=0.34, RR = 5.55), and high-intensity interval training (HIIT) (p=0.28, RR = 4.63).
For live birth rate:
MICT (p=0.82, RR = 10.05), RT (p=0.70, RR = 4.92), HIIT (p=0.66, RR = 4.38)), CET (p=0.45, RR = 2.20), and HICT (p=0.30, RR = 1.55)
The following parameters/markers rank the 5 exercise strategies in order of effectiveness:
- Semen quality parameters were significantly improved after the following types of exercise interventions as compared with the non-intervention group [NON-EX]: CET > MICT > HICT > RT > HIIT
- The following training strategies were significantly better at improving seminal markers of oxidative stress: CET > MICT > HIIT > HICT > RT
- The following training strategies were significantly better at improving seminal markers of inflammation: CET > MICT > HIIT > RT > HICT
- The following training strategies were significantly better at improving measures of body composition and VO2 max: CET > HICT > MICT > HIIT > RT
- There was insufficient evidence of a difference for the selected types of exercise interventions versus NON-EX group for pregnancy and live birth rates in healthy participants.
Conclusion
Combined aerobic and resistance training (CET) was found to be the intervention with the highest probability of being the best approach for improving the male factor infertility.
Clinical practice applications:
- In light of these findings, it is reasonable to propose that infertile men and at-risk populations take part in the top-ranking interventions identified in this analysis.
- For substantial reproductive health benefits, one should consider doing all of the selected types of exercise interventions (CET, MICT, RT, HICT, and HIIT); however, moderate intensity-aerobic exercise and strength training in combination would generally be more favourable to lend clinically significant improvements.
- To add to this, exercise can offer a myriad of other health benefits, is a possibly safe activity and a cost-effective treatment strategy for male factor infertility.
Considerations for future research:
- There was only a small number of relevant trials available for comparison suggesting the need for additional study in this field.
- Further trials are needed to analyse the dose-response impacts of exercise modalities on male reproductive function.
- The results propose several domains for development in the reporting of RCTs addressing the impacts of interventional exercise studies on male reproductive function.
- Heterogeneity of some findings and discrepancy across the included studies was significant. For example, variations in the characteristics of training programs. Future analyses should aim to continue to address this.
- There is a concern that this study may not relate to already active patients with male factor infertility which future studies should address.
Abstract
CONTEXT Mounting evidence from the literature suggests that different types of training interventions can be successful at improving several aspects of male reproductive function in both fertile and infertile populations. OBJECTIVE The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation. DATA SOURCES We searched PubMed, CISCOM, Springer, Elsevier Science, Cochrane Central Register of Controlled Trials, Scopus, PEDro, Ovid (Medline, EMBASE, PsycINFO), Sport Discus, Orbis, CINAHL, Web of Science, ProQuest, and the ClinicalTrials.gov registry for randomized controlled trials (RCTs) that analyzed the impacts of selected types of exercise interventions on markers of male reproductive function and reproductive performance. STUDY SELECTION A total of 336 records were identified, of which we included 7 trials reporting on 2641 fertile and infertile men in the systematic review and network meta-analysis. LEVEL OF EVIDENCE Level 1 (because this is a systematic review of RCTs). DATA EXTRACTION The data included the study design, participant characteristics, inclusion and exclusion, intervention characteristics, outcome measures, and the main results of the study. RESULTS The results of network meta-analysis showed that, compared with a nonintervention control group, the top-ranking interventions for pregnancy rate were for combined aerobic and resistance training (CET) (relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (RR = 26.67), resistance training (RT) (RR = 12.54), high-intensity continuous training (HICT) (RR = 5.55), and high-intensity interval training (HIIT) (RR = 4.63). While the top-ranking interventions for live birth rate were for MICT (RR = 10.05), RT (RR = 4.92), HIIT (RR = 4.38), CET (RR = 2.20), and HICT (RR = 1.55). Also, with the following order of effectiveness, 5 training strategies were significantly better at improving semen quality parameters (CET > MICT > HICT > RT > HIIT), seminal markers of oxidative stress (CET > MICT > HIIT > HICT > RT), seminal markers of inflammation (CET > MICT > HIIT > RT > HICT), as well as measures of body composition and VO2max (CET > HICT > MICT > HIIT > RT). CONCLUSION The review recommends that the intervention with the highest probability of being the best approach out of all available options for improving the male factor infertility was for CET.
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10.
The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis.
Facondo, P, Di Lodovico, E, Delbarba, A, Anelli, V, Pezzaioli, LC, Filippini, E, Cappelli, C, Corona, G, Ferlin, A
Andrology. 2022;10(3):426-440
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Free full text
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Plain language summary
The relationship between type 2 diabetes mellitus and male hypogonadism is well known, whereas the impact of type 1 diabetes mellitus (DM1) on male fertility and testis functions has been less studied. The aim of this study was to systematically review and discuss the available evidence evaluating paternity rate, male gonadal axis, and sperm parameters in men with DM1. This study is a systematic review and meta-analysis of fourteen studies. Results show: - reduced fertility potential in patients with DM1, as they have a lower number of children compared with unaffected population. In fact, the rate of children is statistically significantly lower among men who had been diagnosed with DM1 at an earlier age, according to a longer duration of the disease. - that men with DM1, compared with controls, have significantly lower normal sperm morphology, progressive motility and a trend toward a reduced semen volume, without difference in total sperm count and concentration. Authors conclude that DM1 might impair reproductive health at different levels, including functional sperm alterations definitively leading to reduced fertility rate in these patients.
Abstract
BACKGROUND Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear. OBJECTIVES To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1. MATERIALS AND METHODS A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta-analyzed. RESULTS The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta-analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [-0.36% (-0.66; -0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (-39.13; -28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [-0.51 (-1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto-antibodies, and retrograde ejaculation. DISCUSSION DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies. CONCLUSION Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions.