As persons age, androgen levels decline. Increasingly, exogenous androgens, notably dehydroepiandrosterone (DHEA), are prescribed and sold over the counter to men and women. Endogenous testosterone levels, as well as endogenous DHEA and dehydroepiandrosterone sulfate (DHEAS) levels, have not been linked to cardiovascular events in men or women. Hak and associates studied the relationship between endogenous androgens and aortic atherosclerosis in men and women 55 years and older who were enrolled in the Rotterdam Study to assess the occurrence and determinants of chronic diseases in older adults.

The population-based prospective cohort study enrolled almost 8,000 older adults between 1990 and 1993. Follow-up data collection was performed from 1997 to 1999 for almost 5,000 of the 5,901 invited participants. At baseline, blood sampling for steroid hormones, including DHEAS, testosterone, and sex hormone–binding globulin, was performed on a random sample of 1,432 subjects. Baseline atherosclerosis was measured in 1,252 participants by the extent of calcification noted in the aorta on lateral radiographs of the lumbosacral spine. Smokers were removed from the study, leaving 1,032 persons for analysis. Progression of atherosclerosis was defined as the occurrence of new calcification or enlargement of the length of the calcified area. This type of atherosclerosis assessment has been found on previous studies to be highly specific.

Levels of DHEAS were not associated with severe atherosclerosis in men or women, but severe aortic atherosclerosis risk was lower in men who had higher levels of testosterone. These men also showed a trend toward a lower risk for progression of aortic atherosclerosis. Women with higher levels of testosterone tended to have a greater risk for severe aortic atherosclerosis.

The authors conclude that although there is no clear association between DHEAS and atherosclerosis in men or women, there is a positive association of testosterone levels with severe aortic atherosclerosis in women and an inverse relationship between endogenous testosterone levels and severe aortic atherosclerosis in men. Because aortic atherosclerosis is directly associated with stroke incidence, further studies are needed to determine if men treated with testosterone have fewer harmful atherogenic events.

editor's note: The use of androgen replacement therapy in men remains a controversial topic. Some studies show improvement in bone mass, lipid profile, cognitive process, grip strength, sexual function, and general well-being in older men who are androgen deficient, but these studies had small numbers and were mostly short-term. The overall effect of replacement therapy on cardiovascular disease remains uncertain. A report of the National Institute on Aging Advisory Panel on testosterone replacement in men expresses concern regarding accurate measurement of testosterone levels and the level that actually identifies androgen deficiency. There is also concern about potentially adverse effects, including an increased risk of (1) prostate cancer, (2) significant benign prostatic hypertrophy, (3) erythropoiesis stimulation with resultant hyperviscosity, (4) sleep apnea, (5) cardiovascular disease, and (6) aggressive behavior or inappropriate sexual behavior (Report of National Institute on Aging Advisory Panel on testosterone replacement in men. J Clin Endocrinol Metab October 2001;86:4611–4). Further elaboration is needed on the potentially different effects of androgen supplementation on varying populations, including the very old and the chronically ill. Additional long-term, placebo-controlled trials may help to answer some of these questions.—r.s.