Effects of Testosterone (T) Replacement in Elderly Men: Many studies have shown that, as normal men age, there is a gradual decline in testicular function, including a moderate decrease in total serum T and a larger decline in """"""""bioavailable T"""""""" (T not bound to sex hormone binding globulin, SHBG). A relationship between this age-related decline in androgen levels and age-related changes in physiological parameters such as serum lipids and lipoproteins, muscle mass, and bone mineral density have been proposed, but few studies have directly addressed the impact of declining androgens on these parameters. In addition, the mechanisms responsible for the large decline in """"""""bioavailable T"""""""", despite only modest decline in total serum T, have not been investigated. In a double blind placebo controlled crossover trial, men with screening T less than or equal to 3.5ng/ml will be given additional T and the effects will be studied on (a) parameters indicative of bone turnover, (b) serum lipids, lipoproteins, and lean body mass, (c) prostate size and urinary flow parameters, and (d) sex hormone levels and SHBG structure, binding affinity for androgens, and serum half life. If, as expected, modest T replacement leads to changes indicative of decreased bone turnover or resorption and/or increase in lean body mass, without serious changes to prostate size and serum lipids, a longer trial of T replacement will be done to examine effects on bone density and muscle mass and strength. Studies of Androgen Action Using a 5-Alpha Reductase Inhibitor: Evidence suggests that the permissive androgen in development of benign prostatic hyperplasia (BPH) is dihydrotestosterone (DHT), not T. Recently, a compound that inhibits the conversion of T to DHT (a 5-alpha reductase inhibitor) has been developed. The effect of this compound in the CNS and the subsequent control of gonadotropin secretion are not known. This study will investigate in rats, the ability of the compound to decrease brain levels of DHT and its ultimate effect on gonadotropin levels. This research will give important information about the contribution of DHT to steroid negative feedback regulation of LHRH secretion that could be applicable to man.
| Tenover, J S (1992) Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 75:1092-8 |
| Tenover, J S; Bremner, W J (1991) Circadian rhythm of serum immunoreactive inhibin in young and elderly men. J Gerontol 46:M181-4 |
| Tenover, J S; Bremner, W J (1991) The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men. J Androl 12:258-63 |
| Tenover, J S; Dahl, K D; Vale, W W et al. (1990) Hormonal responses to a potent gonadotropin hormone-releasing hormone antagonist in normal elderly men. J Clin Endocrinol Metab 71:881-8 |
