The medications could protect against prostate cancer but also interfere with PSA test results.
ANAHEIM, Calif.—Statins can significantly reduce PSA levels in healthy men, and the magnitude of this decline is proportional to the extent to which the drugs reduce cholesterol levels, according to researchers.
The PSA-lowering effect of statins could mask the presence of prostate cancer and possibly explain epidemiologic observations of an association between statins and reduced prostate cancer risk, the investigators noted.
A team at Duke University in Durham, N.C., studied 1,214 men (mean age 60 years) prescribed a statin between 1990 and 2006 at the Durham VA Medical Center in Durham, N.C. The study population had a median pre-statin PSA level of 0.9 ng/mL. The mean pre-statin LDL cholesterol level was 144 mg/dL.
All subjects were free of prostate cancer, had not undergone prostate surgery, or had taken medications known to alter hormone levels. Men with pre-statin PSA levels of 10 ng/mL or greater were excluded from the study. The average time between the pre- and post-statin PSA measurement was one year. The average time between starting statins and the post-statin PSA measurement was 214 days.
After starting a statin—usually simvastatin (Zocor)—the median decline in LDL cholesterol was 27.5%, whereas the median decline in PSA levels was 4.1%. For every 10% decline in LDL levels after starting a statin, PSA levels declined 1.6% when adjusted for age. When stratified by quartiles, men with the highest pre-statin PSA levels and the largest drop in LDL experienced a 15.2% average decline in PSA levels.
“This statin-induced decline in PSA may translate into an impaired ability to detect cancer in statin users and certainly this needs to be studied further,” said investigator Robert Hamilton, MD, an associate in clinical research. He cautioned that the new findings are preliminary, but support continued research into stat-tins as a potential prostate cancer preventive agent.
Several mechanisms of action could explain the PSA-lowering effect of statins. One is the link between cholesterol and levels of androgens such as testosterone. Cholesterol is a vital component of androgen synthesis.
“Whether altering the intraprostatic levels of cholesterol may translate into different androgen levels in the prostate is one potential mechanism that has to be studied,” Dr. Hamilton said. “Also, statins can interfere directly with some cellular signaling pathways and so there may be several potential mechanisms that are non-cholesterol mediated.”
In a separate study presented at the meeting, a dose-dependent reduction in prostate cancer risk was found among users of statins, but not among users of other cholesterol-lowering medications. The study—which is the first study to evaluate prostate cancer incidence and PSA levels among statin users in a completely screened population—found a decreased prostate cancer incidence across all categories of prostate tumor grade.
As part of the Finnish Prostate Cancer Screening Trial, the investigators, led by Teemu J. Murtola, MD, of the University of Tampere, identified 78,484 men aged 55-67 years using the Finnish Population Registry in 1996. Of these men, 30,196 were randomly assigned to the screening arm. By the end of 2004, 23,320 men had participated in the screening. Each man was screened with a PSA test at least once. A total of 6,755 men had used statins and 934 used other types of cholesterol-lowering medications (fibrates or resins).
Researchers observed the greatest decrease in the risk for stage T3 malignancy and Gleason sum 5/6 tumors. Serum PSA was lower among users of all groups of cholesterol drugs compared with medication non-users. Statin users experienced a median decline in PSA values of 1.9%-3.0%. The incidence of prostate cancer was 2.8% among statin users compared with 4.7% among subjects who did not use statins.