TROPHIC FACTORS IN AGING - SHOULD OLDER-PEOPLE RECEIVE HORMONAL REPLACEMENT THERAPY

The aging process is associated with significant declines in die level s of many hormones and trophic factors including estrogen, testosteron e, growth hormone (somatropin, somatotropin) and insulin-like growth f actor-I (IGF-1, somatomedin-1, somatomedin-C). Since the classic age-r elated changes resemble the signs and symptoms of endocrine deficiency , it has been hypothesised that some of the negative effects of aging are due to these hormonal deficits. Consequently, the potential role o f hormonal replacement in reversing the deleterious effects of aging d eserves investigation. In old hypogonadal men, preliminary studies hav e shown that testosterone replacement not only improves libido but als o significantly increases musculoskeletal mass and strength. However, adverse effects have included increases in haematocrit and prostate sp ecific antigen. Similarly, short term studies with growth hormone repl acement have shown substantial bodyweight gain, particularly in severe ly malnourished older adults, but longer studies have been limited by adverse effects such as gynaecomastia and carpal tunnel syndrome in a few people. Thus, though both testosterone and growth hormone may have potential roles for frailty syndromes in the elderly, long term clini cal trials are needed to confirm these positive effects and assess the ir safety. On the other hand, the multiple beneficial effects of estro gen replacement in older women such as relieving acute menopausal symp toms and preventing postmenopausal osteoporosis are well recognised. O bservational studies also suggest that estrogen may decrease cardiovas cular disease. However, the optimum duration of treatment and the best way to administer this hormone are still unknown. Also, estrogen may be less effective in senile osteoporosis which primarily results from age-related bone loss. Traditionally, age-related bone loss has been a ttributed to impaired vitamin D activation and decreased calcium absor ption. Thus, it was thought that such bone losses may be ameliorated b y calcium supplementation. However, recent studies suggest that altera tions in local factors affecting bone cell function may also be import ant in the pathogenesis of osteoporosis. An increase in potent bone re sorbing factors, such as the cytokines interleukin-1 and interleukin-6 , has been recently demonstrated in elderly patients with osteoporosis . In these patients, it has been suggested that there may also be a de crease in bone growth factors such as IGF-1 and transforming growth fa ctor-beta. Accordingly, studies are underway to determine whether thes e factors may be useful in the prevention of osteoporosis. Other growt h factors recently identified which may be important in aging include epidermal growth factor, nerve growth factor and fibroblast growth fac tor. Preliminary studies suggest that they may have a role in local wo und healing such as in the treatment of decubitus ulcers. However, sys temic administration may be limited by adverse effects. Finally, despi te the universal decline in the levels of dehyroepiandrosterone (DHEA) with aging, the role of DHEA replacement remains to be defined. Previ ous studies that have suggested an association between low DHEA levels and such degenerative disorders as atherosclerosis, osteoporosis and Alzheimer's disease have yet to be confirmed.