Endocrinology of the Aging Male - 0 views
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All steps beyond the formation of pregnenolone take place in the smooth endoplasmic reticulum
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Cytochrome P450 enzyme, CYP11A is located on the inner mitochondrial membrane and catalyses the rate limiting step of pregnenolone synthesis
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SHBG decreases in response to androgens, and in the presence of hypothyroidism, and insulin resistance.
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The apparent metabolic clearance rate of testosterone is decreased in elderly as compared to younger men
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Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively
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In adult men, there is a well-documented diurnal variation (particularly in younger subjects) in testosterone levels, which are highest in the early morning and progressively decline throughout the day to a nadir in the evening
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Longitudinal studies show an average annual decline of 1–2% total testosterone levels, with decline in free testosterone more rapid because of increases in SHBG with aging
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Androstanediol glucuronide (AAG) declined cross-sectionally with age in the MMAS sample, at 0.6% per year
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The EMAS data show that, consistent with the longitudinal findings of MMAS (Figure 1), the core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total testosterone and progressively blunted free testosterone associated with higher LH
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Androgen deprivation in men with prostate cancer has been associated with increased insulin resistance, worse glycemic control, and a significant increase in risk of incident diabetes
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Low serum testosterone is associated with the development of metabolic syndrome 116, 117 and type 2 diabetes. 118 SHBG has been inversely correlated with type 2 diabetes
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Improvement in insulin sensitivity with testosterone treatment has been reported in healthy 121 and diabetic 122 adult men
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In studies conducted in men with central adiposity, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue leading to decreased triglyceride uptake in central fat depots. 123