Archive | November, 2012

Prostate Cancer and Genetics

Although prostate cancer is the most common cancer found in men, the pathophysiology of this disease remains poorly understood. No definite behavioral or environmental risk factors have been identified, but genetics are an important and likely the strongest contributing factor to the development and progression of the disease. Indeed it has been shown that first degree relatives of affected men are at over two-fold higher risk of developing prostate cancer.

In contrast to other types of cancer, it’s still unclear which individual genes dictate prostate cancer. There are only a few genes with known mutations that cause prostate cancer, and furthermore these mutations explain less than 10% of the risk. Given this, it’s likely that variations in the lower penetrance loci may contribute to disease susceptibility. Multiple case-control genome wide association studies have identified numerous single nucleotide polymorphisms associated with prostate cancer risk. Nevertheless, the problem still lies in how to interpret their combined and individual contributions to disease risk.

Recent studies have examined these potential indicators and have discovered more than 30 loci that may contribute to prostate cancer. However, due to the large number of possible loci, it’s necessary to perform more analyses in a large population of cases and controls testing all of the genetic variants. Hopefully these future studies will reveal a more complete understanding of the individual and cumulative risks associated with these loci.

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Testosterone Replacement Therapy—In Deodorant Form?

Recently, the US Food and Drug Administration (FDA) approved the first underarm testosterone replacement therapy. The treatment is a testosterone 2% topical solution and can be applied to the underarm, much like deodorant.

Results of the study showed that 84.1% of men with hypogonadism increased their testosterone blood levels to within the normal range of men, often after just two weeks of treatment. The treatment also significantly improved mood, sexual desire, sexual activity, and sexual performance.

“The post-treatment changes demonstrated positive responses in sexual desire, sexual activity, mood, and general well-being, underpinning the patient-reported benefits of this treatment. Patient compliance and acceptance of the unique no-touch axilla application technique was very good,” said lead investigator Christina Wang, MD, from the Los Angeles Biomedical Research Institute and professor of medicine at UCLA David Geffen School of Medicine, California.

Testosterone topical solution is found in a metered-dose pump with a no-touch applicator. The recommended initial dose is one pump of the applicator (30 mg) applied to each armpit once daily at the same time every morning. The efficacy of the solution is not affected by application of underarm deodorants or antiperspirants, and grooming such as shaving is not required. But to avoid contamination, deodorant or antiperspirant should be applied before the testosterone solution.

The dosage is determined by serum testosterone concentrations obtained from a blood draw two to eight hours after application after two weeks of the start of therapy.

Virilization in children with secondary exposure to the treated skin is a potential side-effect. Women who are pregnant or might become pregnant should avoid contact with the application site, due to the risk for fetal harm.

In order to avoid contamination, patients should wash their hands with soap and water immediately after applying the testosterone solution. Further, the application site should be covered with clothing after the solution has dried and remain covered until washed. Patients should not swim or wash the underarm area for two hours after application.

Side-effects include hematocrit, headache, diarrhea, vomiting, and serum prostate-specific antigen. Several patients have reported some form of transient application-site reaction during the initial four-month treatment phase, but all cases were mild and resolved quickly on their own.

Patients with benign prostatic hyperplasia should be monitored for worsening of associated signs and symptoms. All patients should be evaluated for prostate cancer at baseline and in accordance with screening practices.

Further, testosterone therapy can decrease blood glucose levels, which may alter insulin requirements in diabetic patients. For those on anticoagulant therapy, testosterone can cause changes in activity, so frequent monitoring is advised. Simultaneous use of corticosteroids can increase fluid retention and should also be monitored cautiously, especially in patients with cardiac, renal, or hepatic disease.

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November 2012
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