Men Have Hormonal Blues Too

Androgen deprivation therapy may be harmful to men with intraepithelial neoplasia

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Most prostate cancers are fed by male hormones called androgens. So treating the disease often involves blocking these hormones. It’s called androgen deprivation therapy (ADT), and it’s been used for decades – but not without controversy.

An animal study – which is very preliminary – suggests that using ADT to prevent prostate cancer may be harmful for men with certain genetic mutations. Furthermore, losing testosterone as a man ages may increase the risk for dangerous pre-cancers.

"Develop a prostate screening plan that makes sense."

The study involving mice was led by Thomas R. Roberts, PhD, co-chair of the Department of Cancer Biology at the Dana-Farber Cancer Institute and professor of biological chemistry and molecular pharmacology at Harvard Medical School in Boston.

Two previous trials have shown that ADT used to ward off prostate cancer does decrease the risk of low-grade prostate cancers, but increases the risks for high-grade tumors. An abnormality called “high-grade prostatic intraepithelial neoplasia” is a major precursor for prostate cancer. The condition may mean that a genetic fault in a gene that’s designed to suppress tumors isn’t working.

Prostate cancer specialist, E. David Crawford, MD, told dailyRx News, “The two trials mentioned were the Prostate Cancer Prevention Trial (PCPT) and Reduction of Prostate Cancer (REDUCE).”

Dr. Crawford says he doesn’t use the drugs tested in these studies for ADT – finasteride (sold under the brand names Proscar and Propecia) and dutasteride (Avodart), both of which are approved to treat enlarged prostate, a condition known as benign prostatic hyperplasia (BPH) . “I really don't consider these agents to be legitimate sources of ADT,” said Dr. Crawford, who is professor of surgery, urology, and radiation oncology, and head of the Section of Urologic Oncology at the University of Colorado Health Sciences Center in Denver.

“As mentioned in both trials, there was a slight increase in high grade cancers. Why? The most plausible reason is that the volume of the prostate was reduced with both drugs in the studies, and so when biopsies were done, it was an overdetection bias,” Dr. Crawford said.

He uses the analogy of it being easier to find a marble in a golf ball-sized gland than it would be to find a marble in an orange.

For this study, Dr. Roberts and his team worked with a mouse model of high-grade prostatic intraepithelial neoplasia and used various types of ADT to treat it. The goal was to shrink the tumors, which occurred, but they returned in a more invasive form.

"Stretching our data even further, these findings suggest that as men age and their testosterone levels decrease, loss of testosterone might actually encourage indolent prostate tumors to become more aggressive," Roberts said. "This suggests that testosterone supplements might be a good thing for the prostate, even though current wisdom suggests the opposite."

Dr. Crawford said in an email, “Both finsteride and dutasteride RAISE the serum testosterone, not lower it, so their last sentence is not true.”

The authors and Dr. Crawford note that this is a preliminary study and that the prostates of mice are very different from those of men.

This preclinical study was published December 19 in Cancer Discovery, a journal of the American Association for Cancer Research.

This study was supported by grants from the Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence award and National Institutes of Health grants.

Dr. Roberts has a commercial research grant and is a consultant/advisory board member of Novartis. Another author also has a commercial research grant from Novartis, receives honoraria for serving on the speakers’ bureau for Sanofi and is a consultant/advisory board member of the National Brain Tumor Society.

Reviewed by: 
Review Date: 
December 20, 2012
Last Updated:
December 20, 2012