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...

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

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