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Jean-Eric Tarride1,2, Mahbubul Haq1, Valerie H Taylor3, Arya M Sharma4, Hamid Reza Nakhai-Pour1, Daria O’Reilly1,2, Feng Xie1,2, Lisa Dolovich2,5,6, Ron Goeree1,21Programs for Assessment of Technology in Health (PATH) Research Institute, St Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada; 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; 3Department of Psychiatry, University of Toronto, Ontario, Canada; 4Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; 5Centre for Evaluation of Medicines, St Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada; 6Department of Family Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaBackground: Obesity is today’s principal neglected public health problem, as a rising proportion of adults will succumb to the medical complications of obesity. However, little is known about the burden of obesity in adults living in Ontario.Objectives: To present an overview of the human and economic burden associated with BMI categories in Ontario, Canada, in terms of socio-demographics, comorbidities, health-related quality of life (HRQoL) and costs associated with hospitalization, same day procedures and physician visits.Methods: The records of all Ontarians who participated in the Canadian Community Health Survey (CCHS), cycle 1.1 and provided consent to data linkage were linked to three administrative databases. Socio-demographic variables, medical characteristics, HRQoL, one year hospitalization, day procedure and physician costs were described per BMI category. Regression analyses were conducted to identify predictors of medical characteristics, HRQoL and costs.Results: More than 50% of adult participants were either overweight or obese in 2000/2001. Obese adults, and to a lesser extent overweight adults, were more likely to report physician-diagnosed comorbid conditions, to use medications, and to have a lower HRQoL. After covariate adjustment, the hospitalization and physician costs were respectively 40% and 22% higher among obese and overweight adults than among normal-weight adults. No statistical cost differences were observed between normal and underweight individuals or between normal and overweight individuals. HRQoL was significantly lower in underweight and obese adults when compared to normal-weight individuals.Conclusions: Due to the large human and economic burden associated with under- or excess-weight, policies promoting healthy weight should remain a priority for governments and employers.Keywords: health-related quality of life, costs, body mass index categories, Ontario

Background: The association between the use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy and the risk of spontaneous abortion remains unclear because of inconsistent research results and the lack of evidence for an effect due to specific types or dosages of nonaspirin NSAIDs. We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women.Methods: Using a nested case-control design, we obtained data from the Quebec Pregnancy Registry for 4705 women who had a spontaneous abortion. For each instance, we randomly selected 10 controls from the remaining women in the registry who were matched by index date (date of the spontaneous abortion) and gestational age. Use of nonaspirin NSAIDs (identified by filled prescriptions) and nonuse were compared. We also looked for associations between different types and dosages of nonaspirin NSAIDs and having a spontaneous abortion. Analyses of associations and adjustment for confounding were done using conditional logistic regression.Results: We identified 4705 cases of spontaneous abortion (352 exposed [7.5%]); 47 050 controls (1213 exposed [2.6%]). Adjusting for potential confounders, the use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk of spontaneous abortion (odds ratio [OR] 2.43, 95% confidence interval [CI] 2.12-2.79). Specifically, use of diclofenac (OR 3.09, 95% CI 1.96-4.87), naproxen (OR 2.64, 95% CI 2.13-3.28), celecoxib (OR 2.21, 95% CI 1.42-3.45), ibuprofen (OR 2.19, 95% CI 1.61-2.96) and rofecoxib (OR 1.83, 95% CI 1.24-2.70) alone, and combinations thereof (OR 2.64, 95% CI 1.59-4.39), were all associated with increased risk of spontaneous abortion. No dose-response effect was seen.Interpretation: Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion. These drugs should be used with caution during pregnancy. [ABSTRACT FROM AUTHOR]

Context: Serum testosterone levels decline significantly with aging. Testosterone supplementation to older men might beneficially affect the aging processes.Objective: To investigate the effect of testosterone supplementation on functional mobility, cognitive function, bone mineral density, body composition, plasma lipids, quality of life, and safety parameters in older men with low normal testosterone levels.Design, Setting, and Participants: Double-blind, randomized, placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherlands.Intervention: Participants were randomly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months.Main Outcome Measures: Functional mobility (Stanford Health Assessment Questionnaire, timed get up and go test, isometric handgrip strength, isometric leg extensor strength), cognitive function (8 different cognitive instruments), bone mineral density of the hip and lumbar spine (dual-energy x-ray absorptiometry scanning), body composition (total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass), metabolic risk factors (fasting plasma lipids, glucose, and insulin), quality of life (Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules), and safety parameters (serum prostate-specific antigen level, ultrasonographic prostate volume, International Prostate Symptom score, serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, hemoglobin, and hematocrit).Results: A total of 207 men completed the study. During the study, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength. Cognitive function and bone mineral density did not change. Insulin sensitivity improved but high-density lipoprotein cholesterol decreased; by the end of the study, 47.8% in the testosterone group vs 35.5% in the placebo group had the metabolic syndrome (P = .07). Quality-of-life measures were no different except for one hormone-related quality-of-life measure that improved. No negative effects on prostate safety were detected.Conclusion: Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects.Trial Registration: isrctn.org Identifier: ISRCTN23688581. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to estimate the excess burden of RA in Ontario, the largest province in Canada., Methods: The records of all adult Ontarians who participated in the Canadian Community Health Survey (CCHS) cycle 1.1 (2000/2001) and provided consent to data linkage were linked to the Ontario Health Insurance Program (OHIP) physician claims database and the Discharge Abstract Database (DAD) In-Patient (i.e. hospitalisation) and Day-Procedure databases. RA individuals (n=233) were identified using CCHS 1.1 and the physician claims database. A control group matched by age, gender and rural/urban status was created with three controls for one case (n=699). Socio-demographic variables, medical characteristics, health-related quality of life (HRQoL) and one-year physician services, hospitalizations and day procedures costs were determined for the RA and non-RA groups. Regression techniques were used to identify predictors of medical characteristics, utility and cost data., Results: The mean age of the population was 59 years and 76% were female. Compared to the matched control group, individuals with RA were statistically more likely to be obese, less educated, physically inactive and have a lower income. RA individuals also reported a statistically higher number of comorbidities and a lower HRQoL. Although no statistical differences were observed between the RA and non-RA groups for the costs associated with hospitalisations, the physician ($1,015 vs. $624, respectively) and day procedure ($102 vs. $51, respectively) costs were statistically higher among RA individuals., Conclusions: These results indicate that the human and economic burden of RA in Ontario is considerable.

Objective: First, to assess the association between the concentration of serum testosterone and the symptoms of testosterone deficiency according to two screening questionnaires. Second, to investigate the effects in elderly men with a low-normal testosterone concentration of testosterone supplementation over a period of 6 months on symptoms of testosterone deficiency according to the screening questionnaires., Design, Setting and Participants: A total of 587 men between 60 and 80 years of age with an eligible serum testosterone measurement and completion of the screening questionnaires were included in the study. Of these 587 men, 237 men with testosterone levels <13·7 nmol/l were included in a double-blind, randomized, placebo-controlled trial of testosterone supplementation., Intervention: One hundred and sixty milligrams per day of oral testosterone undecanoate or a matching placebo for 6 months., Measurements: The Androgen Deficiency in Ageing Males (ADAM) and the Ageing Males' Symptoms rating scale (AMS) questionnaires., Results: There was no significant association between the total testosterone concentration and the scores on the two questionnaires. However, age was significantly associated with the scores on the ADAM (OR 1·14, 95% CI 1·05-1·23) and the AMS (OR 1·03, 95% CI 1·01-1·08) questionnaire. After supplementation with testosterone, there were no effects on the scores on the two questionnaires in the testosterone group compared with the placebo group., Conclusion: The findings do not support the use of the ADAM or AMS questionnaire in the evaluation of late-onset hypogonadism in ageing men. Moreover, 6 months of oral testosterone supplementation had no significant effect on scores of the ADAM and AMS questionnaire in this group of elderly men with low-normal testosterone levels., (© 2011 Blackwell Publishing Ltd.)

Background: Case reports suggest that isotretinoin use is associated with an increased risk of cardiovascular disorders; however, the clinical significance has not been determined., Objective: To determine whether isotretinoin increases the risk of cardiovascular outcomes., Methods: A case crossover study was performed among subjects who filled ≥1 isotretinoin prescription during 1984-2003. Cases were defined as those with a first-ever diagnosis or hospitalization for acute myocardial infarction (MI), stroke, phlebitis/thrombophlebitis, pulmonary embolism (PE) or thrombosis. Exposure to isotretinoin in a 5-month hazard period immediately prior to the index date (calendar date of the diagnosis or hospitalization for the study outcomes) was compared to a 5-month control period. Odds ratios (ORs) along with 95% confidence intervals (CIs) were estimated using conditional logistic regression., Results: Of 30,496 isotretinoin users identified, 872 (3%) cases met the inclusion criteria; 381 (43.7%) had a stroke, 268 (30.7%) phlebitis/thrombophlebitis, 133 (15.3%) MI, 61 (7.0%) PE and 29 (3.3%) thrombosis. When stratified according to type of outcome, ORs were 0.75 (95% CI: 0.38-1.47), 1.31 (95% CI: 0.64-2.69) and 2.00 (95% CI: 0.50-8.00) for stroke, phlebitis/thrombophlebitis and MI, respectively., Conclusion: No statistically significant association was found between isotretinoin and cardiovascular, cerebrovascular and thromboembolic outcomes., (Copyright © 2011 S. Karger AG, Basel.)

Background. This paper presents unpublished clinical and economic data associated with open surgical repair (OSR) in low risk (LR) patients and how it compares with EVAR and OSR in high risk (HR) patients with an AAA > 5.5 cm. Design. Data from a 1-year prospective observational study was used to compare EVAR in HR patients versus OSR in HR and LR patients. Results. Between 2003 and 2005, 140 patients were treated with EVAR and 195 with OSR (HR: 52; LR: 143). The 1-year mortality rate with EVAR was statistically lower than HR OSR patients and comparable to LR OSR patients. One-year health-related quality of life was lower in the EVAR patients compared to OSR patients. EVAR was cost-effective compared to OSR HR but not when compared to OSR LR patients. Conclusions. Despite a similar clinical effectiveness, these results suggest that, at the current price, EVAR is more expensive than open repair for low risk patients.

Background: The risk of relapse of depression or the diagnosis of some other psychiatric disorders during pregnancy necessitates the use of antidepressants despite possible adverse effects. Whether such use increases the risk of spontaneous abortion is still being debated. We evaluated the risk of spontaneous abortion in relation to the use of antidepressants during pregnancy., Methods: Using a nested case-control study design, we obtained data from the Quebec Pregnancy Registry for 5124 women who had a clinically detected spontaneous abortion. For each case, we randomly selected 10 controls from the remaining women in the registry who were matched by the case's index date (date of spontaneous abortion) and gestational age at the time of spontaneous abortion. Use of antidepressants was defined by filled prescriptions and was compared with nonuse. We also studied the classes, types and doses of antidepressants., Results: A total of 284 (5.5%) of the women who had a spontaneous abortion had at least one prescription for an antidepressant filled during the pregnancy, as compared with 1401 (2.7%) of the matched controls (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.83-2.38). After adjustment for potential confounders, we found that the use of antidepressants during pregnancy was associated with an increased risk of spontaneous abortion (OR 1.68, 95%CI 1.38-2.06). Stratified analyses showed that use of selective serotonin reuptake inhibitors alone (OR 1.61, 95% CI 1.28-2.04), serotonin-norepinephrine reuptake inhibitors alone (OR 2.11, 95% CI 1.34-3.30) and combined use of antidepressants from different classes (OR 3.51, 95% CI 2.20-5.61) were associated with an increased risk of spontaneous abortion. When we looked at antidepressant use by type versus no use, paroxetine use alone (OR 1.75, 95% CI 1.31-2.34) and venlafaxine use alone (OR 2.11, 95% CI 1.34-3.30) were associated with an increased risk of spontaneous abortion., Interpretation: The use of antidepressants, especially paroxetine, venlafaxine or the combined use of different classes of antidepressants, during pregnancy was associated with an increased risk of spontaneous abortion.

Background: In spite of the widespread use of antihypertensives during pregnancy, data on their risks and benefits for the newborn are limited. We investigated the risk of major congenital malformations or small-for-gestational-age newborns (SGA) in relation to gestational use of antihypertensives., Methods: Within the Quebec Pregnancy Registry, we conducted two case-control studies. First, cases were defined as major congenital malformations diagnosed during the first year of life and controls were selected from the same cohort; index date was date of delivery. Gestational exposure was defined as filling a prescription for an antihypertensive during the 1st trimester of pregnancy. Next, cases (SGA) were defined as newborns with a birth weight <10th percentile for that gestational age and gender; controls were the newborns with a birth weight > or =10 percentile. Gestational exposure was defined as filling a prescription for an antihypertensive during the 2nd or 3rd trimester. Multivariate logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI)., Results: We found that overall antihypertensives use during the 2nd or 3rd trimesters of pregnancy was associated with a higher risk of SGA (OR 1.53, 95% CI 1.17-1.99). Moreover, selective beta-blocker (OR 6.00, 95% CI 1.06-33.87), alpha beta blocker (OR 2.26, 95% CI 1.04-4.88), or centrally-acting adrenergic agents use (OR 1.70, 95% CI 1.00-2.89) was associated with a higher risk of SGA compared to non-use., Conclusion: Gestational use of antihypertensives, especially beta-blocker, alpha beta blocker, or centrally-acting adrenergic agents, may increase the risk of SGA., (2010 Wiley-Liss, Inc.)

Objective: The goal of this study was to investigate the association between the discontinuation of antihypertensive medication use during the first trimester of pregnancy and the risk of preeclampsia and eclampsia., Study Design: We conducted a nested case-control approach within a cohort that was reconstructed from the linkage of 3 databases. To be included in the study, women had to match the following criteria: (1) between 15-45 years old on the first day of gestation, (2) covered by Québec's Drug Insurance Plan for at least 12 months before and during pregnancy, (3) exposed to an antihypertensive drug on the first day of gestation, and (4) have had a delivery. Multivariate conditional logistic regression models were used to estimate the risk., Results: Adjusting for confounders, the odds ratio was 0.66; 95% confidence interval, 0.27-1.56., Conclusion: Our finding does not support the presence of a statistically significant association between antihypertensive discontinuation during the first trimester of pregnancy and the risk of preeclampsia and eclampsia.

Serum testosterone levels decline significantly with aging and this has been associated with reduced sexual function. We have conducted a double-blind, randomized, placebo-controlled trial to investigate the effect of testosterone supplementation on sexual function in 237 elderly men with a testosterone level <13.7 nmol l(-1). Participants were randomly assigned to receive oral testosterone undecanoate or a placebo for 6 months. A total of 207 men completed the study. After treatment, there were no differences in scores on sexual function between the groups. Subanalysis showed that although a baseline testosterone level in the lowest tertile was associated with significantly lower scores for sexual fantasies, desire of sexual contact and frequency of sexual contact, supplementation of testosterone did not result in improvement on any of these items in this group. In conclusion, the findings do not support the view that testosterone undecanoate supplementation for 6 months to elderly men with low-normal testosterone concentrations favorably affects sexual function.

The use of aspirin and other NSAIDs during the first trimester of pregnancy is widespread, despite inconclusive evidence regarding the possible risks for the baby. We present an overview of the current evidence relating to the associations between aspirin or NSAID use during the first trimester of pregnancy and the risk of congenital malformations. We systematically searched Medline, Embase, the Cochrane Library and the reference lists of all relevant articles from 1966 to March 2008 that examined the association between aspirin and NSAID use during the first trimester of pregnancy and the risk of congenital malformations in humans. We analyzed 30 studies that met the predefined inclusion criteria: 22 case-control studies, seven cohort studies and one randomized, controlled trial. There are not enough human data available to assess the effect of high-dose aspirin and NSAIDs in pregnant women, such as those used in the treatment of rheumatoid arthritis, osteoarthritis and pain relief. This review suggests that the exposure to aspirin or NSAIDs during the first trimester of pregnancy is associated with an increased risk of gastroschisis (aspirin), cardiac malformations (NSAIDs) and orofacial malformations (naproxen).

Elevated plasma homocysteine (tHcy) is considered as a risk factor for cardiovascular events, and has been associated with arterial stiffness and subclinical atherosclerosis in subjects with classical cardiovascular risk factors. The aim of this study is to investigate the association of plasma tHcy with functional and structural changes in the large arteries by measuring aortic pulse-wave velocity (PWV) and carotid artery intima-media thickness (CIMT). In a population-based sample of 376 middle-aged and elderly men, tHcy levels were measured by using fluorescence polarization immunoassay. Aortic stiffness was assessed non-invasively by measuring carotid-femoral PWV with the use of applanation tonometry. CIMT was measured by ultrasonography. We used multivariate linear regression analysis with the log-transformed value of tHcy as the determinant, and aortic PWV and CIMT as outcomes. In the univariate model, PWV increased with increasing tHcy concentration; PWV increased by 2.64 m/s (95% confidence interval (CI) 1.74; 3.54) per unit change in log tHcy. After adjustment for confounders, no statistically significant association remained; PWV increased by 0.42 m/s (95% CI -0.27; 1.11) per unit change in log tHcy. Furthermore, in the univariate model, CIMT increased significantly with increasing tHcy concentration; CIMT increased by 0.19 mm (95% CI 0.11; 0.26) per unit increase log tHcy. This association was attenuated and did not remain significant after additional adjustment for age and cardiovascular confounders (beta=0.06 (95% CI -0.01; 0.13)). The results of this study do not support the presence of an independent relationship between circulating tHcy levels and large artery stiffness and thickness.

High plasma C-reactive protein (hs-CRP) levels and arterial stiffness are risk factors for cardiovascular diseases. Pulse wave velocity (PWV) and augmentation index (AIx) have been found to be elevated in patients with vascular inflammation, diabetes mellitus, hypertension, hypercholesterolemia and in smokers. We investigated the relation of high-sensitivity CRP (hs-CRP) with aortic stiffness in 362 men. The levels of hs-CRP were measured using a nephelometric method. Aortic PWV and AIx were assessed from carotid-femoral segment and radial artery waveforms with the use of the SphygmoCor device. In the crude model, aortic PWV increased significantly with increasing serum hs-CRP levels; PWV increased by 2.48 m/s (95% CI 1.58; 3.38) in the fifth compared to the first quintile of hs-CRP. In the adjusted model, the PWV increased by 0.84 m/s (95% CI 0.13; 1.55) in the fifth quintile compared to the first quintile (P-value was 0.02). In the crude model, AIx increased significantly with increasing serum hs-CRP levels; AIx increased by 7.17% (95% CI 3.72; 10.62) in the fifth versus the first quintile. Adjusted for confounders, AIx remained 4.57% (95% CI 1.32; 7.82) higher in the fifth compared to the first quintile (P-value for trend was <0.01). More adjustment for subclinical atherosclerosis attenuated the beta-coefficient for PWV (difference 0.71 m/s (95% CI 0.01; 1.41), but not for AIx (4.60% (95% CI 1.34; 7.85)). In summary, low-grade inflammation seems to be independently related to increase of aortic artery stiffness over and above traditional risk factors and atherosclerosis.

Background: To determine the effect of oral testosterone supplementation on systemic low-grade inflammation measured by high-sensitive C-reactive protein (hs-CRP) in aging men with low testosterone levels., Methods: Two hundred thirty-seven men aged 60 to 80 years with a testosterone level of <13.7 nmol/L (below the 50th percentile of the population distribution) were recruited into a double-blind randomized placebo-controlled trial. Participants were randomized to either 4 capsules of 40 mg testosterone undecanoate (Andriol Testocaps, NV Organon, Oss, The Netherlands) or placebo daily for 26 weeks. Serum levels of hs-CRP were measured at baseline and at 26 weeks using a near-infrared particle immunoassay of the Synchron LX System (Beckman Coulter, Fullteron, CA)., Results: The median baseline hs-CRP level was 1.95 mg/L (0.30-6.43) in the testosterone group compared with 1.90 mg/L (0.40-5.91) in the placebo group. After 26 weeks of testosterone supplementation therapy, the 2 intervention groups were not statistically significantly different (median hs-CRP 2.20 vs 2.00 mg/L, interquartile range 0.40-6.54 vs 0.50-5.70, P = .36). In subgroup analysis, neither baseline testosterone level, nor age, nor baseline CRP-level modified the effect of testosterone supplementation on CRP levels., Conclusion: Oral testosterone undecanoate supplementation, in dosage of 160 mg daily for 26 weeks, does not increase hs-CRP levels in elderly men.

Background: In women, postmenopausal oestrogen supplementation increases levels of systemic markers of inflammation, which are important predictors of coronary heart disease (CHD) risk. Whether endogenous sex hormone levels in men are also related to systemic subclinical inflammation is still unknown., Objective: We tested the hypothesis that higher endogenous sex hormones levels within the physiological range may be associated with systemic subclinical inflammation., Methods: Circulating sex hormone and high-sensitivity C-reactive protein (hs-CRP) levels were determined in 400 apparently healthy men aged between 40 and 80 years. We used multivariate linear regression analysis with the various sex hormones as determinant, and natural log hs-CRP as outcome., Results: Higher levels of total as well as bioavailable oestradiol (E2) were associated with increased natural log hs-CRP levels, which remained statistically significant after adjustment for age and cardiovascular risk factors. Natural log hs-CRP was 0.26 mg/l higher [95% confidence interval (CI) -0.02 to 0.54] in the fourth than in the first quartile of total E2; the P-value for linear trend was 0.05. For bioavailable E2, the difference in natural log hs-CRP between the fourth and the first quartile was 0.30 mg/l (95% CI 0.03-0.56; P-value for linear trend 0.04). After adjustment for age and cardiovascular risk factors, physiological levels of total (TT) or bioavailable testosterone or dehydroepiandrosterone sulfate (DHEAS) were not associated with hs-CRP., Conclusion: Endogenous total and bioavailable E2 levels are significantly associated with CRP among middle-aged and elder men.

Objective: To investigate whether circulating levels of testosterone (total, bioavailable), estradiol (total, bioavailable), and DHEA sulfate (DHEAS) are associated with fasting plasma homocysteine (tHcy) levels in middle-aged and elderly men., Design: A population-based sample of 400 independently living men between 40 and 80 years of age in a cross-sectional study., Methods: Total testosterone, sex hormone binding globulin (SHBG), and total estradiol were measured by RIA methods and bioavailable testosterone and estradiol were calculated. DHEAS was measured using an immunometric technique. Fasting homocysteine was measured by fluorescence polarization immunoassay. Anthropometric characteristics were also measured and two standardized questionnaires completed, including life-style factors and diet. Linear regression analysis adjusted for age, body mass index (BMI), creatinine clearance, and mean visceral fat was used to assess the association of endogenous sex hormones and fasting plasma homocysteine levels., Results: After adjustment for age, BMI, creatinine clearance, and mean visceral fat no statistically significant association was observed between testosterone (total, bioavailable), DHEAS, and estradiol (total, bioavailable)levels with natural log tHcy (beta = -2 x 10(-3); 95% confidence intervals (CI) -9 x 10(-3); 5 x 10(-3)), (beta = -4 x 10(-3); 95% CI -18 x 10(-3); 9 x 10(-3)), (beta = 3 x 10(-3); 95% CI -6 x 10(-3); 12 x 10(-3)), (beta = -9.3 x 10(-5); 95% CI -1 x 10(-3); 1 x 10(-3)), and (beta = 0.00; 95% CI -3 x 10(-3); 2 x 10(-3)) respectively. Additional adjustment for smoking, alcohol intake, daily physical activity, diabetes mellitus, and hypertension did not change these findings., Conclusion: The results of our study do not support a direct role for circulating sex hormone levels in the regulation of fasting plasma tHcy concentrations in middle-aged and elderly men.

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60-80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety. Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. > or = 100 cm; testosterone level (< 12 versus > or = 12 nmol/L), age (< median versus > or = median), and level of outcome under study (< median versus > or = median). At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m2 and 10.72 nmol/L, respectively.