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The effect of exercise training on cardiometabolic health in men with prostate cancer receiving androgen deprivation therapy: a systematic review and meta-analysis.
Bigaran, A, Zopf, E, Gardner, J, La Gerche, A, Murphy, DG, Howden, EJ, Baker, MK, Cormie, P
Prostate cancer and prostatic diseases. 2021;(1):35-48
Abstract
BACKGROUND Growing evidence suggests that men exposed to androgen deprivation therapy (ADT) have an increased risk of cardiovascular disease. While exercise has shown to attenuate some adverse effects of ADT, the effects on cardiometabolic health have not been systematically evaluated. OBJECTIVE To evaluate the effect of exercise on cardiometabolic health in men with prostate cancer (PCa) receiving ADT. METHODS A systematic literature search of MEDLINE, EMBASE, CINHAL, SCOPUS, WEB OF SCIENCE and SPORTSDICUS from database inception to April 2020 was performed. A quantitative synthesis using Cohens d effect size and a meta-analysis using random-effects models were conducted. RESULTS Overall, fourteen randomised controlled trials (RCTs) and four non-randomised studies were included. Eleven RCTs (n = 939 patients) were included in the meta-analysis. Exercise training improved the 400-m-walk test (MD -10.11 s, 95% CI [-14.34, -5.88]; p < 0·00001), diastolic blood pressure (-2.22 mmHg, [-3.82, -0.61]; p = 0.007), fasting blood glucose (-0.38 mmol/L, [-0.65, -0.11]; p = 0.006), C-reactive protein (-1.16 mg/L, [-2.11, -0.20]; p = 0.02), whole-body lean mass (0.70 kg, [0.39, 1.01]; p < 0.0001), appendicular lean mass (0.59 kg, [0.43, 0.76]; p < 0.00001), whole-body fat mass (-0.67 kg, [-1.08, -0.27]; p = 0.001), whole-body fat percentage (-0.79%, [-1.16, -0.42]; p < 0.0001), and trunk fat mass (-0.49 kg, [-0.87, -0.12]; p = 0.01), compared to usual care. No significant effects on systolic blood pressure or blood lipid metabolism were detected. CONCLUSIONS In a small subset of evaluated studies, exercise may favourably improve some but not all markers of cardiometabolic health. Future exercise intervention trials with cardiometabolic outcomes as primary endpoints are needed to confirm these initial findings.
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Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data.
Islam, RM, Bell, RJ, Green, S, Page, MJ, Davis, SR
The lancet. Diabetes & endocrinology. 2019;(10):754-766
Abstract
BACKGROUND The benefits and risks of testosterone treatment for women with diminished sexual wellbeing remain controversial. We did a systematic review and meta-analysis to assess potential benefits and risks of testosterone for women. METHODS We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for blinded, randomised controlled trials of testosterone treatment of at least 12 weeks' duration completed between Jan 1, 1990, and Dec 10, 2018. We also searched drug registration applications to the European Medicine Agency and the US Food and Drug Administration to identify any unpublished data. Primary outcomes were the effects of testosterone on sexual function, cardiometabolic variables, cognitive measures, and musculoskeletal health. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42018104073. FINDINGS Our search strategy retrieved 46 reports of 36 randomised controlled trials comprising 8480 participants. Our meta-analysis showed that, compared with placebo or a comparator (eg, oestrogen, with or without progestogen), testosterone significantly increased sexual function, including satisfactory sexual event frequency (mean difference 0·85, 95% CI 0·52 to 1·18), sexual desire (standardised mean difference 0·36, 95% CI 0·22 to 0·50), pleasure (mean difference 6·86, 95% CI 5·19 to 8·52), arousal (standardised mean difference 0·28, 95% CI 0·21 to 0·35), orgasm (standardised mean difference 0·25, 95% CI 0·18 to 0·32), responsiveness (standardised mean difference 0·28, 95% CI 0·21 to 0·35), and self-image (mean difference 5·64, 95% CI 4·03 to 7·26), and reduced sexual concerns (mean difference 8·99, 95% CI 6·90 to 11·08) and distress (standardised mean difference -0·27, 95% CI -0·36 to -0·17) in postmenopausal women. A significant rise in the amount of LDL-cholesterol, and reductions in the amounts of total cholesterol, HDL-cholesterol, and triglycerides, were seen with testosterone administered orally, but not when administered non-orally (eg, by transdermal patch or cream). An overall increase in weight was recorded with testosterone treatment. No effects of testosterone were reported for body composition, musculoskeletal variables, or cognitive measures, although the number of women who contributed data for these outcomes was small. Testosterone was associated with a significantly greater likelihood of reporting acne and hair growth, but no serious adverse events were recorded. INTERPRETATION Testosterone is effective for postmenopausal women with low sexual desire causing distress, with administration via non-oral routes (eg, transdermal application) preferred because of a neutral lipid profile. The effects of testosterone on individual wellbeing and musculoskeletal and cognitive health, as well as long-term safety, warrant further investigation. FUNDING Australian National Health and Medical Research Council.
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GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis.
Giagulli, VA, Castellana, M, Perrone, R, Guastamacchia, E, Iacoviello, M, Triggiani, V
Endocrine, metabolic & immune disorders drug targets. 2017;(4):285-296
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Abstract
BACKGROUND AND OBJECTIVE The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficiency (GHD) and in compensated panhypopituitarism including GH deficit. METHODS Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was carried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heterogeneity test (Chi-square statistic). RESULTS Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global outcome D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85). CONCLUSION Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months.
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TRADITIONAL CHINESE MEDICINE COMBINED WITH HORMONE THERAPY TO TREAT PREMATURE OVARIAN FAILURE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.
Kou, MJ, Ding, XF, Chen, JX, Liu, Y, Liu, YY
African journal of traditional, complementary, and alternative medicines : AJTCAM. 2016;(5):160-169
Abstract
BACKGROUND This meta-analysis aimed to provide critically estimated evidence for the advantages and disadvantages of Chinese herbal medicines used for premature ovarian failure (POF), which could provide suggestions for rational treatments. MATERIALS AND METHODS The databases searched included MEDLINE, EMBASE, CNKI, VIP, China Dissertation Database, China Important Conference Papers Database, and online clinical trial registry websites. Published and unpublished randomized controlled trials of traditional Chinese medicine (TCM) combined with hormone therapy (HT) and HT alone for POF were assessed up to December 30, 2015. Two authors extracted data and assessed trial quality independently using Cochrane systematic review methods. Meta-analysis was used to quantitatively describe serum hormone levels and Kupperman scores associated with perimenopause symptoms. RESULTS Seventeen randomized controlled trials involving 1352 participants were selected. Compared with HT alone, although no significant effects were observed in the levels of luteinizing hormone, therapy with TCM combined with HT compared to HT alone effectively altered serum hormone levels of follicle stimulating hormone (P<0.01) and estradiol (P < 0.01), and improved Kupperman index scores (P< 0.01). CONCLUSIONS The reported favorable effects of TCM combined with HT for treating POF patients are better than HT alone.However, the beneficial effects derived from this combination therapy cannot be viewed conclusive. In order to better support the clinical use, more rigorously designed trials are required to provide.
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THERAPY OF ENDOCRINE DISEASE: Testosterone supplementation and body composition: results from a meta-analysis study.
Corona, G, Giagulli, VA, Maseroli, E, Vignozzi, L, Aversa, A, Zitzmann, M, Saad, F, Mannucci, E, Maggi, M
European journal of endocrinology. 2016;(3):R99-116
Abstract
OBJECTIVE The role of testosterone (T) in regulating body composition is conflicting. Thus, our goal is to meta-analyse the effects of T supplementation (TS) on body composition and metabolic outcomes. METHODS All randomized controlled trials (RCTs) comparing the effect of TS on different endpoints were considered. RESULTS Overall, 59 trials were included in the study enrolling 3029 and 2049 patients in TS and control groups respectively. TS was associated with any significant modification in body weight, waist circumference and BMI. Conversely, TS was associated with a significant reduction in fat and with an increase in lean mass as well as with a reduction of fasting glycaemia and insulin resistance. The effect on fasting glycaemia was even higher in younger individuals and in those with metabolic diseases. When only RCTs enrolling hypogonadal (total T <12 mol/l) subjects were considered, a reduction of total cholesterol as well as triglyceride (TGs) levels were also detected. Conversely, an improvement in HDL cholesterol levels as well as in both systolic and diastolic blood pressure was not observed. CONCLUSION Our data suggest that TS is able to improve body composition and glycometabolic profile particularly in younger subjects and in those with metabolic disturbances. Specifically designed studies are urgently needed to confirm this point.
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Effects of low dose versus high dose human growth hormone on body composition and lipids in adults with GH deficiency: a meta-analysis of placebo-controlled randomized trials.
Newman, CB, Carmichael, JD, Kleinberg, DL
Pituitary. 2015;(3):297-305
Abstract
PURPOSE Doses of growth hormone in adults with growth hormone deficiency are now lower than previously. However, it is not clear they are as effective as higher doses. The objective of this meta-analysis was to assess efficacy of low to moderate dose (LD) GH replacement on standard endpoints of GH compared to higher doses. METHODS A meta-analysis was carried out using PubMed, Cochrane and Embase databases from 1960 to 9/23/12. Three reviewers identified randomized double-blind, placebo-controlled trials of 6 months duration. Of 173 publications, 28 representing 22 trials (591 GH-treated patients and 562 placebo) were included. Data were independently extracted by three reviewers. Endpoints were analyzed if ≥4 studies per dose group reported baseline and 6 month data. RESULTS Mean lean body mass (LBM) increased by 2.61 kg in GH-treated subjects versus 0.04 in the placebo group (P < 0.0001). Fat mass (FM) was reduced by -2.19 kg versus 0.31 (GH vs. placebo) (P = 0.0002). Changes in LBM and FM were dose-related (P = 0.02 and 0.007, respectively), high dose (HD) being more effective than low dose (LBM P = 0.03 and FM P = 0.04). In contrast, treatment with GH reduced total cholesterol -0.38 mmol/L versus. 0.01 (placebo) (P < 0.0001), and low density lipoprotein cholesterol (LDL-C) -0.42 mmol/L versus -0.1 (P = 0.0009), but there were no differences between LD and HD GH. CONCLUSIONS LDs of hGH improve total- and LDL-C, and body composition. Higher doses are more effective on body composition, but not lipids.
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Coffee consumption and risk of endometrial cancer: a dose-response meta-analysis of prospective cohort studies.
Zhou, Q, Luo, ML, Li, H, Li, M, Zhou, JG
Scientific reports. 2015;:13410
Abstract
This is a dose-response (DR) meta-analysis to evaluate the association of coffee consumption on endometrial cancer (EC) risk. A total 1,534,039 participants from 13 published articles were added in this meta-analysis. The RR of total coffee consumption and EC were 0.80 (95% CI: 0.74-0.86). A stronger association between coffee intake and EC incidence was found in patients who were never treated with hormones, 0.60 (95% CI: 0.50-0.72), and subjects with a BMI ≥25 kg/m(2), 0.57 (95% CI: 0.46-0.71). The overall RRs for caffeinated and decaffeinated coffee were 0.66 (95% CI: 0.52-0.84) and 0.77 (95% CI: 0.63-0.94), respectively. A linear DR relationship was seen in coffee, caffeinated coffee, decaffeinated coffee and caffeine intake. The EC risk decreased by 5% for every 1 cup per day of coffee intake, 7% for every 1 cup per day of caffeinated coffee intake, 4% for every 1 cup per day of decaffeinated intake of coffee, and 4% for every 100 mg of caffeine intake per day. In conclusion, coffee and intake of caffeine might significantly reduce the incidence of EC, and these effects may be modified by BMI and history of hormone therapy.
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Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials.
Haddad, RM, Kennedy, CC, Caples, SM, Tracz, MJ, Boloña, ER, Sideras, K, Uraga, MV, Erwin, PJ, Montori, VM
Mayo Clinic proceedings. 2007;(1):29-39
Abstract
OBJECTIVE To conduct a systematic review and meta-analysis of randomized trials that assessed the effect of testosterone use on cardiovascular events and risk factors in men with different degrees of androgen deficiency. METHODS Librarian-designed search strategies were used to search the MEDLINE (1966 to October 2004), EMBASE (1988 to October 2004), and Cochrane CENTRAL (inception to October 2004) databases. The database search was performed again in March 2005. We also reviewed reference lists from included studies and content expert files. Eligible studies were randomized trials that compared any formulation of commercially available testosterone with placebo and that assessed cardiovascular risk factors (lipid fractions, blood pressure, blood glucose), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, angina or claudication, revascularization, stroke), and cardiovascular surrogate end points (ie, laboratory tests indicative of cardiac or vascular disease). Using a standardized data extraction form, we collected data on participants, testosterone administration, and outcome measures. We assessed study quality with attention to allocation concealment, blinding, and loss to follow-up. RESULTS The 30 trials included 1642 men, 808 of whom were treated with testosterone. Overall, the trials had limited reporting of methodological features that prevent biased results (only 6 trials reported allocation concealment), enrolled few patients, and were of brief duration (only 4 trials followed up patients for > 1 year). The median loss to follow-up across all 30 trials was 9%. Testosterone use in men with low testosterone levels led to inconsequential changes in blood pressure and glycemia and in all lipid fractions (total cholesterol: odds ratio [OR], -0.22; 95% confidence interval [CI], -0.71 to 0.27; high-density lipoprotein cholesterol: OR, -0.04; 95% CI, -0.39 to 0.30; low-density lipoprotein cholesterol: OR, 0.06; 95% CI, -0.30 to 0.42; and triglycerides: OR, -0.27; 95% CI, -0.61 to 0.08); results were similar in patients with low-normal to normal testosterone levels. The OR between testosterone use and any cardiovascular event pooled across trials that reported these events (n = 6) was 1.82 (95% CI, 0.78 to 4.23). Several trials failed to report data on measured outcomes. For reasons we could not explain statistically, the results were inconsistent across trials. CONCLUSION Currently available evidence weakly supports the inference that testosterone use in men is not associated with important cardiovascular effects. Patients and clinicians need large randomized trials of men at risk for cardiovascular disease to better inform the safety of long-term testosterone use.