Androgens and aging
Introduction
The majority of steroid hormones decline with aging [1]. Over the last decade, there has been increasing enthusiasm that replacement of one or more of these hormones might enhance function and quality of life. This review will concentrate on the role of testosterone replacement in aging men. More briefly, it will examine the effects of testosterone administration to postmenopausal women and the putative role of dehydroepiandrosterone in both sexes.
At the outset it is important to point out that while much of the recently acquired data is exciting, it is still very limited. Thus, like Daedulus cautioned Icarus that if he flew too close to the sun his wax wings might melt, I must caution the reader that while some of the findings are extraordinarily promising, we are still at the stage where we are attempting to determine how close we can come to the sun without melting our wings.
Section snippets
Testosterone decline with aging
It is now generally accepted that testosterone declines with aging, and sex hormone binding globulin (SHBG) increases [2]. This has been demonstrated both cross-sectionally [3] and longitudinally [4]. There is even a more dramatic decline in true free testosterone [5], [6] and bioavailable testosterone [1], [7], [8]. This is because of the increase in SHBG.
To determine testosterone deficiency in older males, one needs to measure either free testosterone (by dialysis or microcentrifuge
Testosterone in females
Testosterone levels decline in females with menopause. This decline is most dramatic following oophorectomy. Testosterone replacement (together with estrogen) improves libido at the menopause [92]. Androgens also decrease hot flushes, increase the general sense of well being and decrease estrogen side effects such as nostalgia and headaches [90]. Testosterone in combination with estrogen improves muscle mass [91] and also increases bone mineral density [92], [93] and bone markers of osteoblast
DHEA and DHEA-S
The most dramatic hormonal declines seen with aging are in the adrenal androgens, DHEA and DHEA-S [94]. These hormones which circulate in high concentrations are still in search of a function. Dehydroepiandrosterone (DHEA) and its sulfate both have potent effects on memory [95] and the immune system [96] in mice. In addition, cross-sectional studies have suggested a role for these hormones in body composition changes and the functional decline that occurs with aging [97].
Despite this, hormonal
Pregnenolone
Pregnenolone is the true mother hormone being derived from cholesterol and the precursor of all steroid hormones. It is a neurosteroid that has been demonstrated in mice to be the most potent memory enhancing agent yet to be identified [95], [98]. Early studies demonstrated that pregnenolone was a useful drug for the treatment of rheumatoid arthritis with minimal side effects [99]. These studies suggest it would be as efficacious and have less side effects than the cyclo-oxygenase-2 inhibitors.
The dawning of the age of the androgens
Clearly there is increasing evidence that androgens may play a role in the functional decline that occurs with aging. Our understanding of the role of testosterone replacement in men is approximately where we were with women 30 years ago. Our knowledge base for the use of testosterone in women and other androgens in either sex is even less well developed. Nevertheless, as long as we remember Daedulus’ warning to Icarus, it is perhaps reasonable on the eve of the Millennium to speculate that the
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