Study finds protective effect for testosterone against heart attack among those at high risk

Tuesday, July 15, 2014. Contrary to recent headlines warning of the potential adverse cardiovascular effects of testosterone replacement, a study reported on July 9, 2014 in the Annals of Pharmacotherapy not only failed to find an increased risk of heart attack in association with testosterone therapy, but even uncovered a protective benefit associated with its use among men at high risk.

A team from the University of Texas Medical Branch at Galveston evaluated data from Medicare beneficiaries aged 66 years or older who received at least one testosterone injection over an eight year period. Among 6,355 men treated with testosterone there was a statistically insignificant 16% lower risk of heart attack requiring hospitalization in comparison with 19,065 matched controls who were never given the hormone. However, among men whose risk of a heart attack was among the top 25% of subjects, treatment with testosterone was associated with a 31% lower risk of the event in comparison with untreated subjects.

"Some investigators have suggested that testosterone therapy may improve cardiovascular health by way of decreasing fat mass, insulin sensitivity, and lipid profile," authors Jacques Baillargeon, PhD, and colleagues write. "Moreover, testosterone may possess anti-inflammatory and anticoagulant properties that may reduce carotid intima media thickness. It is possible that our findings of a protective effect among men in the highest myocardial infarction prognostic group reflect a process whereby testosterone reduces peripheral vascular resistance, thereby reducing stress on the heart among those who have some degree of coronary artery disease."

The findings are important in light of recent expanded labeling of testosterone by the U.S. Food and Drug Administration which included a warning concerning the risk of blood clots. "Our investigation was motivated by a growing concern, in the U.S. and internationally, that testosterone therapy increases men's risk for cardiovascular disease, specifically heart attack and stroke," stated Dr Baillargeon, who is an associate professor of epidemiology in the Department of Preventive Medicine and Community Health at the University of Texas Medical Branch. "This concern has increased in the last few years based on the results of a clinical trial and two observational studies. It is important to note, however, that there is a large body of evidence that is consistent with our finding of no increased risk of heart attack associated with testosterone use."

"This is a rigorous analysis of a large number of patients," he noted. "Our findings did not show an increased risk of heart attack associated with testosterone use in older men. However, large–scale, randomized clinical trials will provide more definitive evidence regarding these risks in the coming years."

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Decreased DHEA sulfate levels linked to greater stroke risk in women

In the American Heart Association journal Stroke, researchers from Brigham and Women's Hospital and Harvard School of Public Health report an association between lower levels of the hormone dehydroepiandrosterone sulfate (DHEAS) and a greater risk of stroke in older women. Their findings appeared online in the journal on May 23, 2013.

The study included women who had no history of stroke upon enrollment in the Nurses' Health Study in 1976. Stored blood samples obtained between 1989 and 1990 were analyzed for DHEA sulfate levels. Four hundred sixty-one participants in whom stroke had occurred over follow-up were matched for age, race, menopausal status and other factors with an equal number of control subjects.

Women who experienced a stroke were likelier to be diabetic and have a history of high blood pressure in comparison with the control group. Among women whose DHEAS levels were among the lowest 25% of participants in the current study, the adjusted risk of experiencing an ischemic stroke was 33% higher than that of women whose levels were among the top 25%. Further adjustment of the analysis increased the percentage to 41%.

Authors Kathryn M. Rexrode MD, MPH and colleagues note that DHEA could influence the development of cardiovascular disease and stroke through mechanisms that include inhibition of the migration and proliferation of vascular wall cells, and stimulation of vascular smooth muscle cell apoptosis, which reduces vascular remodeling subsequent to injury.

"To our knowledge, this is the first report to evaluate DHEAS levels and risk of ischemic stroke," the authors announce. "In this cohort of older women, these results suggest evidence for an inverse association between DHEAS and risk of ischemic stroke, where lower levels of DHEAS were associated with an increased risk of ischemic stroke."

"Additional research is warranted to confirm these associations in other populations," they conclude.

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