Background Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. Methods Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. Results A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. Conclusions In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy.

From measurements of the autocorrelation function and time-averaged intensity of light scattered from aqueous bile salt-lecithin solutions, we deduced the mean hydrodynamic radius (Rh), shape, and polydispersity of bile salt-lecithin mixed micelles as functions of bile salt species, lecithin to bile salt (L/BS) molar ratio, total lipid concentration (0.625-10 g/dL), temperature (20-60 degrees C), and NaCl concentration (0.15-0.6 M). Our data suggest that at low L/BS ratios (0 to approximately 0.6) simple bile salt micelles coexist in varying proportions with minimum-sized mixed micelles (Rh, 18-35 A). These solutions are highly polydisperse and display features dependent upon the particular bile salt species. At high L/BS ratios (greater than 0.6), only mixed micelles are present, and their sizes increase markedly (Rh, 20 leads to 300 A) with increases in L/BS ratio and appear to diverge as the lecithin-bile salt phase limit is approached. The shape of the mixed micelles as deduced from light-scattering measurements and confirmed by transmission electron microscopy is disklike. The radii of the disks, however, are not compatible with Small's model of mixed micellar structure [Small, D.M. (1967a) Gastroenterology 52, 607-a1 but are consistent with a new model proposed here in which bile salts and lecithin interact to form a mixed bilayer disk which is surrounded on its perimeter by bile salts. The inclusion of bile salts in a fixed stoichiometry within the interior of the bilayers is shown to provide a quantitative explanation for the divergence of the mixed micellar sizes, their temperature dependence, and the origin of the lecithin-bile salt phase limit. The influence of total lipid concentration on both mixed micellar size and the lecithin-bile salt phase limit is explained by the "mixed disk" model by taking account of the equilibrium between mixed micelles and bile salt monomers in the intermicellar solution. By use of this concept, deductions of the intermicellar bile salt concentration in taurocholate-lecithin solutions are made and are shown to vary as a function of mixed micellar size and temperature. The range of values obtained, 3-6 mM, is comparable in magnitude to the critical micellar concentration of the pure bile salt.

In women who have undergone oophorectomy and hysterectomy, transdermal testosterone improves sexual function and psychological well-being.

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