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© Johann Ambrosius Barth
31 December 2001 (online)
Endocrinologists consider the aging process to be a programmed dynamic change of hormone secretion and action predominantly characterized by the reduction (male) or cessation (female) of the reproductive function. As the consequences of less effective hormone secretion in the elderly, such as diabetes, osteoporosis, loss of muscularity and reduced mental and emotional capabilities can drastically impair the quality of life, the debate surrounding the appropriate replacement therapy with hormones or hormone-like drugs is currently very intense and controversial.
Whereas diabetes type 2, osteoporosis and conditions related to menopause are of clinical importance and recognized and treated as diseases, the lifelong hormonal replacement therapy (HRT) in postmenopausal women and elderly males is not currently generally accepted. Numerous large prospective clinical studies, particularly those of the American Women's Health Initiative (WHI), will hopefully improve our knowledge. In recent years, premature supplementary medication with GH, dehydroepiandrosterone (DHEA) and melatonin in aging people has been used - in spite of the limited knowledge of the physiology and pathophysiology of adrenopause (reduction of DHEA secretion) and somatopause (reduction of GH and IGF-1).
This issue of ECED contains articles which consider aspects of the important field of endocrinological research: aging and hormones. The contribution by Rolf and Nieschlag reviews the knowledge about the endocrine and reproductive changes in aging men and the possible age-related paternal genetic risks; topics which are rarely investigated compared to the situation in aging women. The authors conclude that there is no evidence for a paternal effect on chromosomal anomalies; however, there is evidence that birth defects, especially those arising from new autosomal mutations, increase with paternal age.
Alesci and Bornstein introduce a new adrenopause hypothesis. They argue that intraadrenal rather than extraadrenal mechanisms are responsible for the dramatic reduction of DHEA production in aging. The increase of the cortisol/DHEA ratio and the decrease in the epinephrine/norepinephrine ratio may in turn affect the local immune cells, e.g., the Th 1/Th 2 ratio. This scenario includes the apoptoses of androgen-producing cells and an increase of free radicals, which further impair the androgen-producing zone and reduce the DHEA production. Alesci and Bornstein's theory, together with the known extraadrenal factors (see Zietz, Hrach, Schölmerich, Straub) is an important part of the complex regulation of DHEA during the human life span.
Zietz, Watzlawek, Palitzsch, Schölmerich and Schäffler examined the possible association of UCP-1 polymorphism and DHEAS concentration. A point mutation within the uncoupling protein-1 (UCP) promotor is possibly involved in the development of diabetes and obesity, and DHEAS stimulated the expression of UCP-1-m-RNA. The authors evaluated the prevalence of the UCP-1 genotypes in 549 type 2 diabetes patients. Their results showed characteristic correlations of DHEAS concentrations and an array of parameters of lipid metabolism in the three UCP-1 genotypes, suggesting a role of the UCP-1 polymorphism in the pathogenesis of obesity and arteriosclerosis.
The role of the age-related increase of interleukin-6 (IL-6) in the secretion of ACTH and adrenal steroids in 48 healthy women and 60 healthy men between the ages of 18 and 75 has been examined by Zietz, Hrach, Schölmerich and Straub. While some steroid production parameters are influenced differently by IL-6 in men compared to women, other parameters are influenced similarly.
Pfeifer, Begerow, Minne, Schlotthauer, Pospeschill, Scholz, Lazarescu and Pollähne examined 237 postmenopausal women with osteoporosis for vitamin D status, trunk muscle strength, body sway and falls and fractures. Steroid hormones were not considered. They found strong evidence for the importance of musculoskeletal rehabilitation, specifically for the trunk muscles, and a training of neuromuscular coordination and balance. These, in addition to the substitution of an hypovitaminosis D seems to be an alternative or a supplementary approach to the treatment of postmenopausal osteoporosis.
The contributions in this ECED issue help illustrate that it will take enormous endocrinological research efforts to understand the aging process and improve the evidence-based hormone replacement therapy - in addition to prescribing a healthy lifestyle including adequate physical and mental exercise.