Lowering Cholesterol Levels May Improve Prostate Cancer Survival

Men who have developed castration-resistant prostate cancer (CRPC) may be able to slow the growth of prostate tumours by reducing their cholesterol levels according to the results of a recent article published in the open access journal PLoS ONE last month.

While the research was conducted in mice, if the results are replicated in human studies, it could open new treatments for castration-resistant prostate cancer, which is notoriously difficult to treat. Castration-resistant prostate cancer (CRPC) arises when hormone therapy is used to treat prostate cancer. The goal of hormone treatment is to deprive the cancerous prostate cells of androgens, a technique known as androgen deprivaton therapy (ADT). Androgens, which are primarily produced in the testicles, fuel the growth of most prostate cancers. While the treatment is initially effective, the cancer eventually becomes resistant and begins to grow again, even when circulating androgen levels are low. Median survival for metastatic CRPC is just 12-18 months.

A team of American researchers speculated that prostate cancer cells may develop the ability to produce androgens themselves from cholesterol. The researchers tested their theory using prostate cancer xenografts in mice. The mice were fed one of four diets for a 12 week period. The diets consisted of a high cholesterol high fat diet with or without ezetimibe (a cholesterol lowering drug) or a low fat no cholesterol diet with or without ezetimibe. Two weeks into the study, the researchers injected human prostate cancer cells into the dorsal flank of the mice.

At the conclusion of the study, the researchers measured the cholesterol levels of the mice, as well as the weight and volume of the implanted tumours. The resulting mice had cholesterol levels varying from around 140 mg/dL in the low fat no cholesterol + ezetimibe group to 200 mg/dL in the high cholesterol high fat group.

The researchers found that cholesterol levels correlated strongly with tumour size. Mice in the lowest quartile for cholesterol levels had tumours averaging 0.79 grams in size compared to 1.32 grams for mice in the highest quartile.

The researchers also measured levels of the androgens testosterone and dihydrotestosterone (DHT) within the tumours. Interestingly testosterone levels within the tumours were found to be significantly higher in mice with cholesterol levels above the median compared to below the median (3.4 pg/mg vs. 2.1 pg/mg). Testosterone levels were also higher in larger tumours compared to smaller tumours.

Tumour DHT levels were also positively correlated with cholesterol levels although the results did not reach statistical significance.

The authors concluded that: “Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the growth of prostate tumors, and suggest that treatment of CRPC may be optimized by inclusion of cholesterol reduction therapies in conjunction with therapies targeting androgen synthesis and the AR.”

Human studies on the impact of cholesterol lowering therapies on prostate cancer survival have not been conducted to date, however several studies have found a link between cholesterol lowering drugs such as statins and a reduced risk of advanced prostate cancer, suggesting that by keeping cholesterol levels in check, the progression of prostate cancer may be slowed. One such study, published in the journal Cancer Epidemiology, Biomarkers & Prevention in 2007, found no link between overall prostate cancer rates and statin use, but that for advanced prostate cancer, statin users were 40% less likely to be diagnosed with the disease than non-users.

Individuals who have recently been diagnosed with prostate cancer should consider embarking on a cholesterol lowering regime, particularly if they have high cholesterol levels. Cholesterol reduction strategies include weight-loss if you are overweight, increasing exercise levels, quitting smoking, substituting red meat for turkey, chicken or fish, limiting intake of fats, particularly saturated and trans fats, increase fiber intake, and consuming products high in plant sterols.