Statins May Have No Effect on Prostate Cancer Risk

Roxanne Nelson

August 16, 2007

August 16, 2007 — Statins do not appear to have a clinically significant effect on levels of circulating androgen and therefore are unlikely to affect circulating androgens and prostate cancer risk through a hormonal mechanism, according to data published in the August issue of Cancer Epidemiology, Biomarkers & Prevention.

Recent epidemiologic analyses have suggested that in addition to lowering cholesterol, statin use might also prevent cancer, but results are inconclusive. Some studies have shown no protective effect at all, while a recent large cohort study found that men who used statins had a substantially reduced risk for metastatic or aggressive prostate cancer. The reduction in risk was strongly associated with duration of statin use.

"The research our team did may inform the debate over statins and prostate cancer but does not resolve it," explained lead author Susan Hall, PhD, a research scientist from the New England Research Institutes, in Watertown, Massachusetts. "We did not study prostate cancer as an outcome directly — we studied a hypothesized biologic pathway between statins and prostate cancer."

"The study results may help inform theories on how statins may protect against prostate cancer by suggesting that any protective pathway, if it exists, is not through androgen suppression, although further studies should be done," Dr. Hall told Medscape.

To date, there have been no epidemiologic studies that examined the effect of statin drugs on circulating androgen levels. Dr. Hall and colleagues investigated the hypothesis that statin use might reduce serum androgen levels and their carrier protein, sex hormone–binding globulin (SHBG). The researchers evaluated data from the Boston Area Community Health (BACH) Survey, a population-based, cross-sectional epidemiologic study funded by the National Institutes of Health that contained data collected between 2002 and 2005.

There were 1812 men who met the inclusion criteria for the study, and of this cohort, 237 (12.4%) used statins. The most commonly used statin was atorvastatin (73.4%), followed by simvastatin (16.4%), pravastatin (5.1%), lovastatin (2.7%), fluvastatin (1.9%), and rosuvastatin (1.3%).

As compared with the rest of the cohort, the average statin user was older, had higher body-mass index, and had more comorbidities such as diabetes, hypertension, and cardiovascular disease. They also tended to be using more prescription medications.

The researchers were unable to find a relationship between statin use and serum total testosterone, free testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, and SHBG, which was measured in all study participants. Even though they did initially observe a significant association between statin use and total testosterone, it was not sufficiently robust after they controlled for covariates such as age, body-mass index, time since awakening, and a history of cardiovascular disease and diabetes.

"We found that the effect of statins on total testosterone in our study was small and not significant and could be explained mainly by the presence of other risk factors for low testosterone," said Dr. Hall. "The most important risk factors in our study were larger body size, diabetes, and heart disease. In other words, being on statins was a marker for having other risk factors for low testosterone. People with diabetes are more aggressively treated with statins, for example."

An association between SHBG and statin use was noted, even after covariates were controlled for. SHBG levels in men using statins were 11% lower than those in nonusers. To rule out possible confounding by central adiposity, the researchers examined the effect of waist circumference, but that did not alter the results. While a direct effect of statins on SHBG metabolism in this study cannot be entirely ruled out, they point out that statin intervention trials have not demonstrated any effect on SHBG levels in men with dyslipidemia.

"The public health significance of the study is that it provides some reassurance that statins may not have a large significant impact on serum androgens in community-dwelling men, although further studies should be done," said Dr. Hall. "Statins are the most commonly used prescription drug in the world, and the use is long-term; the evidence for or against an impact on prostate cancer is still accumulating, and further work needs to be done."

The BACH Survey was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

Cancer Epidemiol Biomarkers Prev. 2007;16:1587–1594. Abstract



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