Androgens and Coronary Artery Disease

126

Background: The combination of male gender, obstructive sleep apnoea (OSA) and obesity magnifies cardiometabolic risk. There has been no systematic study evaluating whether testosterone therapy can improve cardiometabolic health in obese men with OSA by improving body composition, visceral abdominal fat and insulin sensitivity. Objective: To assess body compositional and cardiometabolic effects of testosterone treatment in obese men with severe OSA. Design: An 18-week randomised, double-blind, placebo-controlled and parallel group trial in 67 men. Methods: Participants (ageZ49G12 years, apnoea hypopnoea indexZ39.9G17.7 events/h, BMIZ31.3G5.2 kg/m

Section: Discussionmentioning

confidence: 58%

Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea: a randomised placebo-controlled trial

Hoyos

Yee

Phillips

et al. 2012

126

“…Our finding of a strong inverse association of total and free testosterone concentrations with non-esterified free fatty acids is consistent with this hypothesis. Exogenous testosterone may also have a favourable effect on the lipid profile, although HDL levels have sometimes decreased (34). Whether testosterone mediates its effect on blood pressure indirectly through the association of testosterone with the metabolic syndrome or directly through effects on the vascular endothelium is not known (34).…”

Section: Discussionmentioning

confidence: 99%

Sex hormones, inflammation and the metabolic syndrome: a population-based study

Laaksonen

Niskanen²,

Punnonen³

et al. 2003

390

290

Objective: Mild hypoandrogenism in men is associated with features of the metabolic syndrome, but the association with the metabolic syndrome itself using an accepted definition has not been described. Design: Men with the metabolic syndrome were identified and testosterone and sex hormone-binding globulin (SHBG) levels were determined in a population-based cohort of 1896 non-diabetic middleaged Finnish men. Results: Calculated free testosterone and SHBG were 11% and 18% lower (P , 0.001) in men with the metabolic syndrome (n ¼ 345, World Health Organisation definition). After categorisation by tertiles and adjusting for age and body mass index, total and free testosterone and SHBG were inversely associated with concentrations of insulin, glucose, triglycerides, C-reactive protein (CRP) and CRP-adjusted ferritin and positively associated with high-density lipoprotein cholesterol. Men with free testosterone levels in the lowest third were 2.7 (95% confidence interval (CI) 2.0-3.7) times more likely to have the metabolic syndrome in age-adjusted analyses, and 1.7 (95% CI 1.2 -2.4) times more likely even after further adjusting for body mass index. Exclusion of men with cardiovascular disease did not alter the association. The inverse association of SHBG with the metabolic syndrome was somewhat stronger. Conclusions: Low testosterone and SHBG levels were strongly associated not only with components of the metabolic syndrome, but also with the metabolic syndrome itself, independently of body mass index. Furthermore, sex hormones were associated with inflammation and body iron stores. Even in the absence of late-stage consequences such as diabetes and cardiovascular disease, subtle derangements in sex hormones are present in the metabolic syndrome, and may contribute to its pathogenesis.

“…Studies on SHBG gene polymorphisms have shown an association of the SHBG gene promoter polymorphism with the severity of CAD, as well as early markers of atherosclerosis in postmenopausal women (34,35). However, discussing studies on the clinical relevance of SHBG in cardio-and cerebro-vascular disease is not part of this review and the reader is referred to recent reviews (36,37).…”

Section: Severity and Mortality Of Cardio-and Cerebro-vascular Diseasementioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period

Παππά

Alevizaki

2012

Objective: Cardio-and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio-and cerebro-vascular disease in the postmenopausal period. Design and methods: We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. Results: The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Conclusions: Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio-and cerebro-vascular disease remains an interesting field of future research.