Low Cholesterol May Lower the Risk of Aggressive Prostate Cancer

Men who have low cholesterol levels have a decreased risk of aggressive prostate cancer, a recently published study suggests.

The study, which included 5,586 men aged 55 years and older who participated in the Prostate Cancer Prevention Trial (PCPT), showed that men whose cholesterol levels were below 200 mg/dL had a 59% decreased risk of aggressive prostate cancer compared with men who had higher cholesterol levels, researchers reported in the journal Cancer Epidemiology, Biomarkers & Prevention. Cholesterol levels did not affect the risk of non-aggressive cancers.

The researchers, led by Elizabeth A. Platz, ScD, MPH, of Johns Hopkins Bloomberg School of Public Health in Baltimore, concluded that their findings add to the literature supporting a role for cholesterol in the development of prostate cancer that has a worse prognosis.

The PCPT, which started in 1993, investigated whether finasteride, a medication used to treat enlarged prostates, could prevent prostate cancer. Investigators randomly allocated subjects to receive either finasteride or placebo (dummy pills) for seven years. The study showed that finasteride decreased the incidence of prostate cancer by 25%.

The analysis by Dr. Platz’s team focused on men in the placebo arm, but they also examined the relationship between cholesterol and high-grade cancer in the finasteride-treated group and found no link between the two.

A prostate cancer researcher not involved with the new study, Stephen J. Freedland, MD, of the Duke Prostate Center at Duke University Medical Center in Durham, N.C., said the study by Dr. Platz and her colleagues is consistent with previous research and “provides some of the strongest data to date” linking high cholesterol with an increased risk of high-grade prostate cancer.

Dr. Freedland said he has started to mention this association to men with high cholesterol when counseling them about whether to get screened for prostate cancer. “I say to patients, ‘There are increasing data to suggest that high cholesterol may increase your risk of aggressive prostate cancer.’”

As for whether a man should be placed on a cholesterol-lowering drug called a statin to lower his risk of aggressive prostate cancer, Dr. Freedland observed, “If he has high cholesterol, he should probably be on a statin anyway.” It is unknown whether statin treatment would further reduce the risk in men with low cholesterol, he said.

Previous studies suggest that statin use may protect against advanced prostate cancer. For example, one study showed that statin use was associated with a 43% decreased risk of advanced prostate cancer and a 65% decreased risk of fatal or metastatic prostate cancer.

Dr. Freedland—whose research has focused on risk factors for prostate cancer and its recurrence following treatment, as well as on possible ways to prevent prostate cancer with medications—said it is biologically plausible for cholesterol to be involved in the pathogenesis of high-grade prostate cancer. Cholesterol is the precursor for testosterone, which promotes prostate tumor growth, Dr. Freedland said. Hypothetically, high cholesterol concentrations could mean greater testosterone production, he said. Evidence is mounting that high-grade, castration-resistant tumors can make their own testosterone from cholesterol, he noted.

Cholesterol also may directly stimulate tumor growth, he explained. In addition, all new cells need cholesterol as part of their membranes. “Thus, lower cholesterol means it is harder for the cells to replicate,” he said. “Given that high-grade tumors grow faster, this could explain why low cholesterol only reduced the risk of high-grade disease. All of these mechanisms suggest that it is indeed plausible that high cholesterol could promote more aggressive cancers.”