Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials

Background Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. Methods A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. Results Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). Conclusions The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy

Trends in Mortality from Septicaemia and Pneumonia with Economic Development: An Age-Period-Cohort Analysis

BackgroundHong Kong population has experienced drastic changes in its economic development in the 1940s. Taking advantage of Hong Kong’s unique demographic and socioeconomic history, characterized by massive, punctuated migration waves from Southern China, and recent, rapid transition from a pre-industrialized society to the first ethnic Chinese community reaching ‘‘first world’’ status over the last 60 years (i.e., in two or three generations), we examined the longitudinal trends in infection related mortality including septicemia compared to trends in non-bacterial pneumonia to generate hypotheses for further testing in other recently transitioned economies and to provide generalized aetiological insights on how economic transition affects infection-related mortality. Methods We used deaths from septicemia and pneumonia not specified as bacterial, and population figures in Hong Kong from 1976–2005. We fitted age-period-cohort models to decompose septicemia and non-bacterial pneumonia mortality rates into age, period and cohort effects. Results Septicaemia-related deaths increased exponentially with age, with a downturn by period. The birth cohort curves had downward inflections in both sexes in the 1940s, with a steeper deceleration for women. Non-bacterial pneumoniarelated deaths also increased exponentially with age, but the birth cohort patterns showed no downturns for those born in the 1940s. Conclusion The observed changes appeared to suggest that better early life conditions may enable better development of adaptive immunity, thus enhancing immunity against bacterial infections, with greater benefits for women than men. Given the interaction between the immune system and the gonadotropic axis, these observations are compatible with the hypothesis that upregulation of the gonadotropic axis underlies some of the changes in disease patterns with economic development

Breast cancer incidence and mortality in a transitioning Chinese population: current and future trends

Background Projections of future trends in cancer incidence and mortality are important for public health planning. Methods By using 1976–2010 data in Hong Kong, we fitted Poisson age-period-cohort models and made projections for future breast cancer incidence and mortality to 2025. Results Age-standardised breast cancer incidence (/mortality) is projected to increase (/decline) from 56.7 (/9.3) in 2011–2015 to 62.5 (/8.6) per 100 000 women in 2021–2025. Conclusions The incidence pattern may relate to Hong Kong’s socio-economic developmental history, while falling mortality trends are, most likely, due to improvements in survival from treatment advancement and improved health service delivery

2006-2007 Drake Memorial Library Annual Report

2006-2007 annual report of Drake Memorial Library of The College at Brockport

testosterone, cardiovascular, men, trial

Background Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. MethodsA systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. Results Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). ConclusionsThe effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy

Age-Period-Cohort Projections of Ischaemic Heart Disease Mortality by Socio-Economic Position in a Rapidly Transitioning Chinese Population

BackgroundWith economic development and population aging, ischaemic heart disease (IHD) is becoming a leading cause of mortality with widening inequalities in China. To forewarn the trends in China we projected IHD trends in the most economically developed part of China, i.e., Hong Kong. MethodsBased on sex-specific IHD mortality rates from 1976 to 2005, we projected mortality rates by neighborhood-level socio-economic position (i.e., low- or high-income groups) to 2020 in Hong Kong using Poisson age-period-cohort models with autoregressive priors. ResultsIn the low-income group, age-standardized IHD mortality rates among women declined from 33.3 deaths in 1976–1980 to 19.7 per 100,000 in 2016–2020 (from 55.5 deaths to 34.2 per 100,000 among men). The rates in the high-income group were initially higher in both sexes, particularly among men, but this had reversed by the end of the study periods. The rates declined faster for the high-income group than for the low-income group in both sexes. The rates were projected to decline faster in the high-income group, such that by the end of the projection period the high-income group would have lower IHD mortality rates, particularly for women. Birth cohort effects varied with sex, with a marked upturn in IHD mortality around 1945, i.e., for the first generation of men to grow up in a more economically developed environment. There was no such upturn in women. Birth cohort effects were the main drivers of change in IHD mortality rates. ConclusionIHD mortality rates are declining in Hong Kong and are projected to continue to do so, even taking into account greater vulnerability for the first generation of men born into a more developed environment. At the same time social disparities in IHD have reversed and are widening, partly as a result of a cohort effect, with corresponding implications for prevention

Growth Environment and Sex Differences in Lipids, BodyShape and Diabetes Risk

BackgroundSex differences in lipids and body shape, but not diabetes, increase at puberty. Hong Kong Chinese are mainly first or second generation migrants from China, who have shared an economically developed environment for years, but grew up in very different environments in Hong Kong or contemporaneously undeveloped Guangdong, China. We assessed if environment during growth had sex-specific associations with lipids and body shape, but not diabetes. Methodology and Principal FindingsWe used multivariable regression in a population-based cross-sectional study, undertaken from 1994 to 1996, of 2537 Hong Kong Chinese residents aged 25 to 74 years with clinical measurements of ischaemic heart disease (IHD) risk, including HDL-cholesterol, ApoB, diabetes and obesity. Waist-hip ratio was higher (mean difference 0.01, 95% CI 0.001 to 0.02) in men, who had grown up in an economically developed rather than undeveloped environment, as was apolipoprotein B (0.05 g/L, 95% CI 0.001 to 0.10), adjusted for age, socio-economic status and lifestyle. In contrast, the same comparison was associated in women with lower waist-hip ratio (20.01, 95% CI 20.001 to 20.02) and higher HDL-cholesterol (0.05 mmol/L, 95% CI 0.0004 to 0.10). The associations in men and women were significantly different (p-values,0.001). There were no such differences for diabetes. ConclusionsGrowth in a developed environment with improved nutrition may promote higher sexsteroids at puberty producing an atherogenic lipid profile and male fat pattern in men but the opposite in women, with tracking of increased male IHD risk into adult life

Moderate Alcohol Use and Cardiovascular Disease from Mendelian Randomization

Background Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD) and cardiovascular disease (CVD). However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use. Methods We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day) with CVD risk factors (blood pressure, lipids and glucose) and morbidity (self-reported IHD and CVD) among men in the Guangzhou Biobank Cohort Study. Results ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6). Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI) 0.02 to 0.08) and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07) but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74), LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08), log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08) or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03), self-reported CVD (odds ratio (OR) 0.98, 95% CI 0.76 to 1.27) or selfreported IHD (OR 1.10, 95% CI 0.83 to 1.45). Conclusion Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose