Tag Archive | "androgen"

No Relationship Between Small Prostate Size and High Grade Cancer

Previously, radical prostatectomy series have shown an inverse relationship between prostate size and high grade cancer.  It was suggested that smaller sized prostates arise in a low androgen environment, which enables development of more aggressive cancer.  A recent study by a team of authors from Stanford University School of Medicine in the Journal of Urology, however, shows that small prostate size is not associated with high grade cancer.  The authors argue that previous observations are the result of ascertainment bias driven by prostate specific antigen performance.

The study’s authors analyzed 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (723) and T2 (681) disease who had surgery between 1988 and 2002 and underwent detailed morphommetric mapping by a single pathologist.  They used multivariate linear regression to analyze the effects of age, prostate weight and prostate specific antigen on total and high grade cancer volume and percentage of high grade disease.

Patients who underwent biopsy due to abnormal prostate specific antigen (stage T1c had a prostate weight that was negatively associated with total cancer volume, which is the volume of high grade disease and percentage of high grade disease.  For patients who underwent biopsy based on abnormal rectal examination (stage T2), these relationships were not present.

The authors conclude that improved prostate specific antigen performance for high grade disease results in ascertainment bias in patients with T1c disease.  For this reason, the relationship between prostate size and high grade disease may be a result of grade dependent performance of prostate specific antigen rather than true tumor biology.

Posted in Prostate HealthComments (1)

New Findings Show that Prostate Cancer Can Adapt to Survive Hormone Therapy

A recent study at UCLA’s Jonsson Comprehensive Cancer Center, researchers found that when a common type of prostate cancer was treated with conventional hormone ablation therapy that blocks androgen production or androgen receptor (AR) function, which increases the growth of the tumor, the cancer was able to adapt to this treatment by activating a survival cell pathway.  This particular type of prostate cancer, in which the PTEN tumor suppressor gene is inactivated, accounts for about 40 to 50 percent of primary prostate cancers and 70 to 90 percent of cancers that become resistant to hormone therapy, also known as castration-resistant prostate cancers.  According to Hong Wu, M.D., Ph.D., the study’s senior author, these prostate cancers could be more effectively treated using a combination of drugs that target the AR cell signaling pathway and the adapted survival pathway.

According to Wu, the discovery goes against conventional wisdom about the way PTEN negative or PTEN null prostate cancer operates.  Previously, most hypotheses suggested that PTEN regulates the function of the androgen receptor pathway, which turns out to be the opposite of the study’s findings.  The findings of this study were thus surprising in showing that PTEN loss represses AR signaling and causes cancer cells to become less dependent on the AR for survival.  According to David J. Mulholland, a postdoctoral fellow in Wu’s lab and first author of the study, it has important implications for prostate patients with late stage disease, who often become resistant to hormone ablation therapy.  The men who die of prostate cancer are the ones who become resistant to therapy and, as a result, the cancer spreads or metastasizes to other places, usually to the bones.

The five-year study was first modeled in a mouse model created at Wu’s laboratory in which PTEN and AR are absent in the epithelium.  The team then replicated the findings using samples from cancerous prostates removed from patients, which was done in coloration with researchers at UCLA and the Specialized Program of Research Excellence (SPORE) in prostate cancer.  They found similar results in both bases.  The study was funded by the National Institutes of Health, the Department of Defense, the Prostate Cancer Foundation, the California Institute for Regenerative Medicine and Jean Perkins Foundation.

Over 217,000 American men will be diagnosed with prostate cancer this year, out of which 32,000 will die.

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Dutasteride and Finasteride May Contribute to Irreversible Sexual Dysfunction in Men

Dutasteride (Avodart), a drug frequently prescribed to treat enlarged prostate and Finasteride (Proscar and Propecia); a drug frequently prescribed to treat hair loss may contribute to erectile dysfunction, depression and loss of libido. Symptoms may even persist after the medication stopped.

This is according to a study led by Abdulmaged M. Traish, a professor of biochemistry and urology at Boston University School of Medicine. The team searched for available medical literature for reports of sexual side effects associated with Finasteride and Dutasteride. Of the men taking the drugs, 8% reported erectile dysfunction and 4.2% reported reduced libido while those taking the placebo only 4% of men reported erectile dysfunction and 1.8% of men reported reduced libido. The researchers also noted that reduced ejaculation, reduced semen volume and depression were also reported by some men.

The drugs (Dutasteride and Finasteride) work by blocking androgen but androgen is needed for erectile function, libido and ejaculation, and for just feeling good.

Traish said “as a physician you have a responsibility to take the time and explain to your patient that maybe not everyone will have these side effects, but you may, and in some cases they are irreversible””.

Dr. Bruce R. Kava, an associate professor of urology at the University Of Miami Miller School Of Medicine agreed that “these drugs do cause some of these problems but they haven’t convinced me yet, based on the data, because they don’t have any long term data”. He added that most urologists discuss potential side effects with their patients but usually “don’t discuss long term consequences that are irreversible, because most of us have not been aware of any long term problems from these drugs”.

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