Lowered testosterone in male obesity: Mechanisms, morbidity and management Tang Fui MN, Dupuis P, Grossmann M - Asian J Androl - 0 views
www.ajandrology.com/article.asp
Testosterone male obesity overweight men hormone hormones low T Low T
shared by Nathan Goodyear on 15 Jan 14
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The number of overweight people is expected to increase from 937 million in 2005 to 1.35 billion in 2030
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Similarly the number of obese people is projected to increase from 396 million in 2005 to 573 million in 2030
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By 2030, China alone is predicted to have more overweight men and women than the traditional market economies combined
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diacylglycerol O-acyltransferase 2 (DGAT2), mechanistically implicated in this differential storage, [10] is regulated by dihydrotestosterone, [11] suggesting a potential role for androgens to influence the genetic predisposition to either the MHO or MONW phenotype.
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bariatric surgery achieves 10%-30% long-term weight loss in controlled studies
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The fact that obese men have lower testosterone compared to lean men has been recognized for more than 30 years
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Reductions in testosterone levels correlate with the severity of obesity and men
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epidemiological data suggest that the single most powerful predictor of low testosterone is obesity, and that obesity is a major contributor of the age-associated decline in testosterone levels.
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healthy ageing by itself is uncommonly associated with marked reductions in testosterone levels
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obesity blunts this LH rise, obesity leads to hypothalamic-pituitary suppression irrespective of age which cannot be compensated for by physiological mechanisms
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Reductions in total testosterone levels are largely a consequence of reductions in sex hormone binding globulin (SHBG) due to obesity-associated hyperinsulinemia
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although controversial, measurement of free testosterone levels may provide a more accurate assessment of androgen status than the (usually preferred) measurement of total testosterone in situations where SHBG levels are outside the reference range
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SHBG increases with age
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marked obesity however is associated with an unequivocal reduction of free testosterone levels, where LH and follicle stimulating hormone (FSH) levels are usually low or inappropriately normal, suggesting that the dominant suppression occurs at the hypothalamic-pituitary level
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adipose tissue, especially when in the inflamed, insulin-resistant state, expresses aromatase which converts testosterone to estradiol (E 2 ). Adipose E 2 in turn may feedback negatively to decrease pituitary gonadotropin secretion
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diabetic obesity is associated with decreases in circulatory E 2
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In addition to E 2 , increased visceral fat also releases increased amounts of pro-inflammatory cytokines, insulin and leptin; all of which may inhibit the activity of the HPT axis at multiple levels
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In the prospective Massachusetts Male Aging Study (MMAS), moving from a non-obese to an obese state resulted in a decline of testosterone levels
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weight loss, whether by diet or surgery, increases testosterone levels proportional to the amount of weight lost
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fat is androgen-responsive
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low testosterone may augment the effects of a hypercaloric diet
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In human male ex vivo adipose tissue, testosterone decreased adipocyte differentiation by 50%.
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Testosterone enhances catecholamine-induced lipolysis in vitro and reduces lipoprotein lipase activity and triglyceride uptake in human abdominal adipose tissue in vivo
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in men with prostate cancer receiving 12 months of androgen deprivation therapy, fat mass increased by 3.4 kg and abdominal VAT by 22%, with the majority of these changes established within 6 months
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severe sex steroid deficiency can increase fat mass rapidly
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bidirectional relationship between testosterone and obesity
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increasing body fat suppresses the HPT axis by multiple mechanisms [30] via increased secretion of pro-inflammatory cytokines, insulin resistance and diabetes; [19],[44] while on the other hand low testosterone promotes further accumulation of total and visceral fat mass, thereby exacerbating the gonadotropin inhibition
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androgens may play a more significant role in VAT than SAT
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men undergoing androgen depletion for prostate cancer show more marked increases in visceral compared to subcutaneous fat following treatment
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Interesting: low T increases VAT, yet T therapy does not reduce VAT, yet T therapy reduces SAT.
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irisin, derived from muscle, induces brown fat-like properties in rodent white fat
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androgens can act via the PPARg-pathway [37] which is implicated in the differentiation of precursor fat cells to the energy-consuming phenotype
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low testosterone may compound the effect of increasing fat mass by making it more difficult for obese men to lose weight via exercise
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pro-inflammatory cytokines released by adipose tissue may contribute to loss of muscle mass and function, leading to inactivity and further weight gain in a vicious cycle
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Sarcopenic obesity, a phenotype recapitulated in men receiving ADT for prostate cancer, [55] may not only be associated with functional limitations, but also aggravate the metabolic risks of obesity;
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observational evidence associating higher endogenous testosterone with reduced loss of muscle mass and crude measures of muscle function in men losing weight
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genuine reactivation of the HPT axis in obese men requires more substantial weight-loss
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A number of intervention studies have confirmed that both diet- and surgically-induced weight losses are associated with increased testosterone, with the rise in testosterone generally proportional to the amount of weight lost
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men, regardless of obesity level, can benefit from the effect of weight loss.
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inconsistent effect of testosterone on VAT