A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population.Fifteen hypogonadal men (mean age 68 Ϯ 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65 Ϯ 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone Ͻ60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months. The main outcomes measured included grip strength, hemoglobin, prostate-specific antigen, leptin, and memory.Testosterone improved bilateral grip strength (P Ͻ 0.05 by ANOVA) and increased hemoglobin (P Ͻ 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean Ϯ SEM: Ϫ2.0 Ϯ 0.9 ng/dL vs. 0.8 Ϯ 0.7 ng/dL; P Ͻ 0.02). There were no significant changes in prostatespecific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit.Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks. (J Clin Endocrinol 82: [1661][1662][1663][1664][1665][1666][1667] 1997) A DECLINE in testicular function with a consequent decline in testosterone and bioavailable testosterone is recognized as a common occurrence in older men (1-5). Although there is great interindividual variability in testosterone and bioavailable testosterone (BT) levels with advancing age, half of healthy men between the ages of 50 -70 yr will have a BT level below the lowest level seen in healthy men who are 20 -40 yr of age (6).Studies have suggested that androgens have many important physiological actions including effects on sexual function, muscle, body composition, bone, bone marrow, prostate, and the central nervous system (7-11). However, data are sparse regarding the effects of the age-associated decline in testosterone secretion on these target systems.Few studies have assessed the role of testosterone replacement in older hypogonadal men and whether putative improvements in strength, body composition, and bone will occur without significant risks in this patient population. In a 6-month cross-over trial of testosterone, Tenover (12) found no change in muscle strength, an increase in hematocrit and prostate-specific antigen (PSA), a decrease in total cholesterol, and an increase in weight and lean body mass without changes in percent body fat. Morley et al. (13) found an increase in right-hand grip strength, an increase in hematocrit, and a d...

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In men with erectile dysfunction, transurethral alprostadil therapy resulted in erections in the clinic and in intercourse at home.

These preliminary findings support the need for long term studies of testosterone therapy in older hypogonadal males.

The relation of the reproductive endocrine system to impotence in older men was examined by measuring the concentrations of testosterone (T), bioavailable testosterone (BT), LH, and PRL and body mass index (BMI) in 57 young controls (YC), 50 healthy potent older controls attending a health fair (HF), and 267 impotent patients (SD). The SD and HF had markedly reduced mean T and BT values compared to YC. When adjusted for age and BMI there was no difference in BT between potent and impotent older men. The percent BT was much higher in YC than in the older groups. While the percent BT rose significantly with increased T in YC, it was inversely related to T in the older subjects, suggesting that increased sex hormone-binding globulin binding was a primary event leading to a low BT. Forty-eight percent of HF and 39% of SD were hypogonadal, as defined by a mean BT of 2.5 SD or more below the mean of YC (less than or equal to 2.3 nmol/L). Ninety percent of these had LH values in the normal range, suggesting hypothalamic-pituitary dysfunction. Thirty-four SD and six each of YC and older control volunteers (OC) underwent GnRH testing. Older subjects showed impaired responsiveness to GnRH compared to YC. A low basal LH level correlated very highly with hyporesponsiveness to GnRH. Thus, secondary hypogonadism and impotence are two common, independently distributed conditions of older men.

To determine the complications, toxicities, and compliance of long term testosterone replacement in hypogonadal males, we retrospectively assessed 45 elderly hypogonadal men receiving testosterone replacement therapy and 27 hypogonadal men taking testosterone. Hypogonadism was defined as a bioavailable testosterone serum concentration of 72 ng/dL or less. Both groups received baseline physical examinations and blood tests. The testosterone-treated group received 200 mg testosterone enanthate or cypionate im every 2 weeks, and follow-up examinations and blood samplings were performed every 3 months. The control group had a single follow-up blood test and physical examination. There was no significant difference in the initial blood tests in the two groups. At 2 yr follow-up, only the hematocrit showed a statistically significant increase in the testosterone-treated group compared to the control group (P < 0.001). A decrease in the urea nitrogen to creatinine ratio and an increase in the prostate-specific antigen concentration was not statistically significant. Eleven (24%) of the testosterone-treated subjects developed polycythemia sufficient to require phlebotomy or the temporary withholding of testosterone, one third of which occurred less than 1 yr after starting testosterone treatment. There was no significant difference in the incidence of new illness in the two groups during the 2-yr follow-up. Although self-assessment of libido was dramatically improved in the testosterone-treated group (P < 0.0001), approximately one third of the subjects discontinued therapy. In conclusion, testosterone replacement therapy appears to be well tolerated by over 84% of the subjects. Long term testosterone replacement to date appears to be a safe and effective means of treating hypogonadal elderly males, provided that frequent follow-up blood tests and examinations are performed.

A cross-sectional study of 216 impotent men aged 40 to 79 years (mean age 60.9 years) was conducted to determine if there are age-related changes in clinical and hormonal parameters in an impotent population. There was a slight increase in the degree of sexual dysfunction with age, with complete erectile failure occurring in a larger percent of the 60- and 70-year-olds than in the younger patients (41% vs 27% for the 40 year olds, P less than .05). No patient above the age of 70 years reported any full erections, even of short duration. In contrast, reported levels of libido did not vary significantly with age. Abnormal penile Doppler studies diagnostic of vasculogenic impotence were found in 17.8% of the patients tested, and an additional 17.8% were found to have evidence suggestive of a vascular etiology. These abnormal vascular findings were associated with an extremely high prevalence of clinically apparent atherosclerosis in this population. In 22.9% of the subjects, an abnormal vascular response was found only on exercise, ie, a "pelvic steal", which only occurred above the age of 50 years. There was a marked age-related alteration in the concentration of testosterone (T) and bioavailable testosterone (BT), but no statistically significant change in the levels of gonadotropins with age. An increase in the prevalence of eugonadotropic hypogonadism with age was found, which suggested an increasing prevalence of hypothalamic pituitary dysfunction in this patient group. For both vascular and hormonal changes (such as low T and BT), the greatest changes appear to occur after the age of 50.(ABSTRACT TRUNCATED AT 250 WORDS)