Endocrine Abstracts

In men, aging is associated with a gradual and progressive decline in serum testosterone (T) levels, such that an increasing proportion of aging men have T levels below the normal range in young men, i.e. in the hypogonadal range. The age-related de-cline T levels is associated with alterations in body composition (decreasing lean and increasing fat mass), decreases in muscle mass and strength, bone mineral density (BMD), sexual function, and cognitive function, and depressed mood and well-being that mimic manifestations of androgen deficiency in younger hypogonadal men and that improve with T replacement. Thus, it is hypothesized that the decline in T levels with aging contributes to age-related alterations in body function. To test this hypothesis, we and others have per-formed short-term, randomized controlled trials of T treatment in small numbers of older men with low-normal to low T levels. These studies reported consistent improvements in body composition and some found improvements in muscle mass, strength, BMD and sexual function. We reported that T treatment improved spatial and verbal memory in healthy older men with low-normal to low serum T and in men with mild cognitive impairment or Alzheimer’s disease. Recently, we also found that T improved depression in older men with mild or subsyndromal depression. Following recommendations from the Institute of Medicine in the US, a large multi-center randomized controlled study is planned of short-term T treatment in older hypogonadal men with consistently low serum T levels and symptoms of androgen deficiency. The short-term outcomes will be physical, sexual and cognitive function, and quality of life. The major concern with T treatment in older men is the potential risk of stimulating prostate cancer growth. However, age-related decline in T levels is associated with a seemingly paradoxical increase in the prevalence of prostate cancer with age. Because metastatic prostate cancer is responsive initially to androgen deprivation, there is concern that T treatment in older men will stimulate the growth of sub-clini-cal localized prostate cancer. Given this concern, we and others have embarked on studies to more closely examine the intraprostatic androgen milieu and cellular dynamics in older hypogonadal men on androgen treatment. Finally, we recently found that low serum T is associated with an increased risk of mortality in male veterans, and are proceeding with further studies to confirm this in a general population and assess the risk of low T on cardiovascular mortality. However, large ran-domized, placebo-controlled studies are needed to assess the long-term clinical risks of T treatment in older hypgonadal men.