Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of transdermal dihydrotestosterone on left ventricle mass and its systolic and diastolic function as well as on the results of treadmill stress test was assessed in eleven males with coronary artery disease. DHT treatment for 3 months resulted in significant decrease in isovolumetric relaxation time (0.150+/-0.37 s vs. 0.135+/-0.03 s; p < 0.05) indicating the improvement of left ventricle diastolic function. Left ventricle mass and systolic function indices remained unchanged. There was improvement in myocardial ischemia, time to 1 mm ST segment depression increased (p < 0.05) and ST/HR slope decreased (p < 0.01). Correlation coefficients between testosterone concentration at the beginning of the study and differences in selected parameters of ECG stress test were as follows: for T and increased total exercise time (r= -0.83, p=0.002), for T and increased maximum workload (r= -0.84, p=0.001), for T and increased time to 1 mm ST segment depression (r= -0.75, p=0.009) and for T and decreased ST/HR slope (r=0.68, p=0.02).
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PMID:Dihydrotestosterone treatment in men with coronary artery disease. II. Influence on myocardial ischemia and left ventricle. 1532

Despite being generally perceived as detrimental to the cardiovascular system, testosterone has marked beneficial vascular effects; most notably it acutely and directly causes vasodilatation. Indeed, men with hypotestosteronaemia can present with myocardial ischemia and angina which can be rapidly alleviated by infusion of testosterone. To date, however, in vitro studies have failed to provide a convincing mechanism to account for this clinically important effect. Here, using whole-cell patch-clamp recordings to measure current flow through recombinant human L-type Ca2+ channel alpha(1C) subunits (Ca(v)1.2), we demonstrate that testosterone inhibits such currents in a concentration-dependent manner. Importantly, this occurs over the physiological range of testosterone concentrations (IC50 34 nM), and is not mimicked by the metabolite 5alpha-androstan-17beta-ol-3-one (DHT), nor by progesterone or estradiol, even at high (10 microM) concentration. L-type Ca2+ channels in the vasculature are also important clinical targets for vasodilatory dihydropyridines. A single point mutation (T1007Y) almost completely abolishes nifedipine sensitivity in our recombinant expression system. Crucially, the same mutation renders the channels insensitive to testosterone. Our data strongly suggest, for the first time, the molecular requirements for testosterone binding to L-type Ca2+ channels, thereby supporting its beneficial role as an endogenous Ca2+ channel antagonist in the treatment of cardiovascular disease.
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PMID:Molecular requirements for L-type Ca2+ channel blockade by testosterone. 1717 68

This narrative review presents an overview of current knowledge on fertility and reproductive hormone changes in aging men, the factors driving and modulating these changes, their clinical consequences, and the benefits and risks of testosterone (T) therapy. Aging is accompanied by moderate decline of gamete quality and fertility. Population mean levels show a mild total T decline, an SHBG increase, a steeper free T decline, and a moderate LH increase with important contribution of comorbidities (e.g., obesity) to these changes. Sexual symptoms and lower hematocrit are associated with low T and are partly responsive to T therapy. The relationship of serum T with body composition and metabolic health is bidirectional; limited beneficial effects of T therapy on body composition have only marginal effects on metabolic health and physical function. Skeletal changes are associated primarily with estradiol and SHBG. Cognitive decline is not consistently linked to low T and is not improved by T therapy. Although limited evidence links moderate androgen decline with depressive symptoms, T therapy has small beneficial effects on mood, depressive symptoms, and vitality in elderly patients with low T. Suboptimal T (and/or DHT) has been associated with increased risk of stroke, but not of ischemic heart disease, whereas an association with mortality probably reflects that low T is a marker of poor health. Globally, neither severity of clinical consequences attributable to low T nor the nature and magnitude of beneficial treatment effects justify the concept of some broadly applied "T replacement therapy" in older men with low T. Moreover, long-term safety of T therapy is not established.
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PMID:Aging and the Male Reproductive System. 3088 1