Statins Fail to Cut the Androgens that Fuel Prostate Cancer

WATERTOWN, Mass. Aug. 10 -- Statins do not seem to reduce production of circulating testosterone and related androgens, researchers here reported.

Although the men using statins in a large population-based study had lower androgen levels, the associations vanished in a covariate analysis and were probably due to other health problems, Susan A. Hall, Ph.D., of the New England Research Institutes here, and colleagues, reported in the August issue of Cancer Epidemiology, Biomarkers & Prevention.

It is possible the statins may lower prostate cancer risk through one or more alternative pathways, but reduction in male hormones does not seem to be one of them, Dr. Hall said.

Although some studies have shown no effect of statins on prostate cancer, a recent large cohort study showed a substantially reduced risk of metastatic disease among statin users.

Reduction of cholesterol, a testosterone precursor, might influence the biology and progression of prostate cancer, the researchers wrote. However, they said, the effect of statins on circulating androgen levels in men has not been considered in an epidemiologic study.

In a narrow study focused solely on hormone levels, the researchers determined whether statin use affected levels of circulating androgens and their carrier protein, sex hormone-binding globulin (SHBG).

The study included 1,812 men derived from the population-based Boston Area Community Health (BACH) survey. From 2002 through 2005, the BACH survey collected data on 5,500 men and women with equal representation of African Americans, Caucasians, and Hispanics.

Statin exposure was collected through self-reports or interviewer-recorded information, or both. Multivariate linear models were then constructed to account for potential confounding.

Only 237 men (12.4%) used statins (95% confidence interval 10.3-14.9). On average, statin users were older, had a larger body mass index (BMI), more chronic illnesses, and used more medications.

The researchers measured serum levels of total testosterone, free testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, and SHBG. They found no relationship between statin use and free testosterone, dehydroepiandrosterone sulfate, or LH.

A significant association between statin use and total testosterone was seen at first but was did not hold after covariate control in a multivariate model that included age, body mass index, time since awakening, and history of cardiovascular disease, and diabetes (-5.5%; CI, -13.2% to 2.9%).

Men with a higher BMI, diabetes, and cardiovascular disease tend to have lower testosterone levels, and this largely accounted for the drop in testosterone in statin users," Dr. Hall said.

However, after a similar adjustment, SHBG levels among statin users were 11% lower than among nonusers (-10.6%; CI, -18.8 to -1.6%). The findings remained robust even after controlling for BMI and other covariates, the researchers said.

Although it was not possible to rule out a direct effect of statins on the protein carrier, intervention trials have not shown such an effect on men with dyslipidemia.

A more likely explanation, the researchers said, is the effect of circulating insulin on SHBG production. Statin users tend to have higher levels of circulating insulin than non users, and higher levels would drive down SHBG levels in these individuals.

The statins used in this study included mainly atorvastatin (Lipitor) for 73.4%, followed by simvastatin (Zocor) for 16.4%, as well as pravastatin (Pravachol), lovastatin (Mevacor), fluvastatin (Lescol) and rosuvastatin (Crestor).

Statin users were different from nonusers on most covariates, the researchers said. They were likely to be older, have a higher BMI, and were more likely to have clinically low total testosterone and comorbid diseases, such as diabetes, hypertension, and cardiovascular ills. Consequently they were more likely to be taking other medications than non-statin users.

Study limitations included the lack of information about dose and duration of use. The relatively small sample of 237 statin users limited examination of subgroups, and the preponderance of atorvastatin limited the ability to consider other types of statins.

In assessing the results, the researchers said that despite the lack of effects of statins on serum androgen levels in this study, "we cannot rule out the possibility that statins may modulate steroid synthesis in prostate tissues."

The mechanisms by which prostatic tissue maintains tissue androgens may include metabolism of adrenal androgens or fresh synthesis from cholesterol.

Statins could influence disease progression by several different effects including increasing prostate epithelial cell sensitivity to apoptosis.

This study suggests that a protective pathway offered by statins, if it exists, is not through androgen suppression. Thus further studies of statin use in prostate cancer are warranted, Dr. Hall said.