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On average there is a small
Aging is associated with degenerative changes in multiple organ systems. The rate and extent to which these occur depend on genetics, the presence of other disease processes, and the accumulated effects of socioeconomic, lifestyle, and environmental factors. Although there is no equivalence in men of the abrupt cessation of cyclical ovarian activity that occurs in women, a variable and inconsistent decrease in testosterone with increasing age is observed, albeit that even at very advanced age, sexual and reproductive function may be within normal limits. The age-related decrease in testosterone is primarily due to testicular dysfunction, at least in the absence of disorders that affect the hypothalamic-pituitary-testicular (HPT) axis, for example obesity, although some reduction in central responsiveness of the HPT axis may also occur. The extent to which an age-related decrease in testosterone has direct consequences for physical or cognitive function as well as mood and overall quality of life, and the level of testosterone at which these occur remains incompletely resolved, as does the role of the testosterone supplementation.
This chapter discusses the endocrinology of the aging male, with particular focus on the biology and central regulation of the HPT axis, and the epidemiology of sex hormone changes, with implications for diagnosis and management of hypogonadism in aging men. Since testosterone is the most important androgen from a biological perspective and assays are widely available, this chapter focuses on testosterone, with attention paid to other androgens and other sex hormones as appropriate.
In a normal adult male, neurons in the preoptic area and the medial basal region of the hypothalamus secrete gonadotrophin-releasing hormone [GnRH] in a pulsatile manner. The periodicity and amplitude of GnRH secretion determine the pattern of secretion of the gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), from the gonadotroph cells of the anterior pituitary.
It has been suggested, but not proven, that neuronal GnRH outflow in healthy men is reduced by 33–50%
Proper assessment of HPT axis functioning relies critically on accurate assessment of analytes in human serum, and to a lesser extent and for specific syndromes (e.g., hypogonadism), on medical history or patient self-report.
Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively. A small and variable fraction is said to circulate as free testosterone. One or another of these circulating fractions of testosterone have been
Because of the complex interrelations of the sex hormones with other hormone systems, common chronic diseases of aging (cancer, CVD, diabetes, depression, hyperlipidemia, arthritis), and associated risk factors for chronic disease (obesity, sedentariness, nutritional deficiency, smoking), there is still little consensus to what constitutes a normal sex hormone profile for an aging male. There is no male equivalent of the menopause, and even in very old men with healthy active lifestyles plasma
In men with classical hypogonadism, treatment is clearly indicated and men should be monitored appropriately. See Chapter X (Bhasin). There is considerable debate about the appropriateness of testosterone in aging men. The long-term safety or efficacy of testosterone replacement in aging men with late-onset hypogonadism has not been established, but as noted above, small-scale clinical studies suggest that testosterone may have beneficial effects. On average there is a smallPractice points
ABA is a consultant to Lilly USA, LLC (Indianapolis, IN). GAW is a consultant to Lawley Pharmaceuticals (Perth WA, Australia) and received speaking fees and research support from Bayer Schering Pharma AG and Organon.
Supported by Award Number R01AG020727 from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health. GAW is in receipt of project grant support from the National Health and Medical Research Council of Australia and the Australian Research Council.
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