Although alterations of circulating sex steroids have been reported in aging men, it is not known to what extent reported changes may represent effects of variables other than aging. We have measured sex hormone levels, serum binding, the testosterone (T) response to hCG, and basal LH levels in 69 male volunteers, aged 25-89 yr, without alcoholism, obesity, chronic illness, or severe prostatic disease, and not using potentially interfering medications. In our study there was no effect of age on serum T, 5 alpha-dihydrotestosterone, estrone, or estradiol. Binding of T to T-binding globulin increased slightly with age, but not enough to decrease the free T index (fraction free X T concentration). Basal serum LH rose significantly. The T response to hCG suggested a somewhat diminished Leydig cell reserve with age, a conclusion consistent with the LH elevation. Our failure to detect the decreased T and free T index or increased estrogens reported by others could reflect afternoon rather than morning sampling, but is more likely to be due to our use of exceptionally healthy volunteers. We suggest that factors other than aging might have influenceed the data previously reported, and that aging per se need not be associated with altered sex steroid levels in the human male.

IMPORTANCE Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown.OBJECTIVE To determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS Testosterone's Effects on Atherosclerosis Progression inAging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012.INTERVENTIONS One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL. MAIN OUTCOMES AND MEASURESCoprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health-related quality of life.RESULTS Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% CI, −0.003 to 0.003, P = .89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, −10.8 Agatston units/year; 95% CI, −45.7 to 24.2; P = .54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in testosterone group.CONCLUSIONS AND RELEVANCE Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men.

Aging diminishes hormone secretion and target cell responsiveness, possibly due to loss of cell membrane fluidity or alteration of membrane phospholipids affecting signal transduction. We investigated whether a high omega-3 polyunsaturated fatty acid diet would improve endocrine function in 6 men and 6 women aged over 60 years. Subjects first ate an isocaloric control diet for 6 weeks, followed by an 8-week experimental diet, which included 720 g of fatty fish weekly plus 15 ml of sardine oil daily. In the last week, we measured RBC membrane fatty acids on each diet, performed pituitary, adrenal, hepatic, and Leydig cell endocrine provocative testing, and assayed selected cytokines. We also assessed insulin sensitivity utilizing octreotide insulin suppression testing and assessed free fatty acid (FFA) responses to isoproteronol. Insulin sensitivity increased significantly after 8 weeks on the omega-3 diet and FFA responses trended lower. Serum C-reactive protein was significantly reduced and a trend towards lower IL-6 was noted. No differences were found in other metabolic parameters, adiponectin levels, or hormone responses. We conclude that, in older people, high omega-3 consumption increases insulin sensitivity, may reduce FFA mobilization by catecholamines, and reduces inflammatory markers, but did not alter endocrine responsiveness after 8 weeks.