Low testosterone linked to long-term risk of death in over-50s

Low testosterone linked to long-term risk of death in over-50s

The results of a study presented on June 5, 2007 at The Endocrine Society for publication in their ENDO 07 Research Summaries Book determined that men over 50 whose levels of the hormone testosterone are low had a greater risk of dying within an eighteen year period than men with higher levels.

University of California, San Diego School of Medicine chief of the Division of Epidemiology Elizabeth Barrett-Connor, MD and colleagues evaluated data from nearly 800 men aged 50 to 91 who enrolled in the Rancho Bernardo Heart and Chronic Disease Study in the 1970s. Twenty-nine percent of the participants had testosterone levels at the lower limit of the normal range for their age at the beginning of the 1980s. These men experienced a 33 percent greater risk of dying from any cause over the ensuing 18 years than men with higher levels. Participants with decreased testosterone had a greater incidence of elevated inflammatory cytokines, as well as greater waist girth and other metabolic syndrome risk factors.

"Conventional wisdom is that women live longer because estrogen is good and testosterone is bad," Dr Barrett-Connor stated. "We don’t know. Maybe the decline in testosterone is healthy and comes with older age. Maybe the decline is bad and is associated with chronic diseases of aging."

"The new study is only the second report linking deficiency of this sex hormone with increased death from all causes, over time, and the first to do so in relatively healthy men who are living in the community," announced coauthor Gail Laughlin, PhD, who presented the findings. "We have followed these men for an average of 18 years and our study strongly suggests that the association between testosterone levels and death is not simply due to some acute illness."

New EPCA-2 blood test for PCa 94% Accurate

New, EPCA-2, blood test for Prostate Cancer 94% Accurate

A new prostate test that relies on measuring levels of a blood protein called EPCA-2 accurately found cancer 94% of the time, according to a study released Wednesday.

By Susan Brink
Times Staff Writer

April 26, 2007

A new prostate test that relies on measuring levels of a blood protein called EPCA-2 accurately found cancer 94% of the time, a significant improvement over the current PSA test, according to a study released Wednesday.

Each year, about 1.6 million men undergo biopsies because they test positive on a PSA test — but only about 230,000 of them actually have cancer.

The new test for EPCA-2 — or early prostate cancer antigen — not only detected prostate cancer but also determined whether it had spread to other parts of the body, according to the study published in the journal Urology.

"It could allow us to help patients decide if they need a biopsy or if it's tame or has the ability to invade outside the prostate," said Robert H. Getzenberg, director of research at the James Buchanan Brady Urological Institute at Johns Hopkins University in Baltimore and a coauthor of the study.

The test still faces large-scale clinical trials and review by the Food and Drug Administration, but it could be available in early 2008, said Getzenberg, who is a consultant to Seattle-based Onconome Inc., which is developing the test technology.

Prostate cancer is the second leading cause of cancer death in men after lung cancer, according to the American Cancer Society. About 27,000 die from prostate cancer a year, the society said.

Rectal examination and the PSA — or prostate specific antigen — test, which was approved in 1994, have been the primary methods of detecting the cancer.

But questions about the accuracy of the PSA test have been building. It has a high level of false positives and misses about 15% of prostate cancers.

Many false positive results require patients to undergo a biopsy, an unpleasant surgical procedure where prostate samples are taken for analysis.

Another problem is that the PSA test does not distinguish between the cancer's aggressive form, which is frequently fatal, and a slow-growing form that patients can safely live with.

"The PSA is a flawed marker. Everybody agrees with that," said Dr. Laurence Klotz, chief of urology at Sunnybrook Health Sciences Center in Toronto. "The search for a better marker is intense."

In hunting down a new marker, Getzenberg said his team found that the EPCA-2 protein was structurally different in cancerous and normal prostate cells.

The researchers measured the EPCA-2 levels in the blood of 385 men who were known have cancer or were free of it.

Men who had an elevated EPCA-2 test indeed had cancer 94% of the time, compared with only about 19% of men with an elevated PSA result, reported in previous studies. The test falsely sounded an alarm 3% of the time, according to the report.

The EPCA-2 test missed about 6% of existing cancers. The PSA test misses about 15% of existing cancers, according to previous studies.

"It's pretty exciting," said Dr. Mark Scholz, a Marina del Rey oncologist specializing in prostate cancer. "PSA testing has led to over-treatment. With a more accurate test like this, one of the big pluses right away would be fewer biopsies."

But Scholz said the PSA still has value. "If you do two tests, you have a greater likelihood of finding the truth," he said.

Other prostate tests are in the pipeline, including a urine-based genetic test and another blood test.


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susan.brink@latimes.com

Prostate Biopsies may cause Metastases

Inflammation caused by Biopsy may be involved in prostate cancer metastasis

A report published online on March 19, 2007 in the journal Nature described the findings of University of California San Diego researchers that the inflammation associated with the immune system's attack on prostate tumors could be involved in their metastasis. It has been hypothesized that genetic changes within the cancer cell result in metastasis, but this does not explain metastases that occur years after the primary tumor.

Working with a mouse model of prostate cancer, professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, Michael Karin, PhD, and his colleagues discovered a signaling pathway that increased prostate tumor metastases. They found that a cytokine called RANK ligand, produced by inflammatory cells, initiates a chain reaction in which a protein kinase known as IKKa is activated to enter the cancer cell nucleus and reduce the expression of the antimetastatic gene Maspin.

"An excellent inverse correlation between IKKa activation and Maspin production was detected, such that advanced prostate cancer cells contain high amounts of activated IKKa in their nuclei and express little or no Maspin," Dr Karin stated. "Maspin is a very potent inhibitor of metastasis; in a patient with metastasis, cells have found a way to turn off Maspin, which may depend on invasion of the tumor with RANK ligand-producing cells that activate IKKa."

"Our findings suggest that promoting inflammation of the cancerous tissue, for instance, by performing prostate biopsies, may, ironically, hasten progression of metastasis," Dr Karin observed. "We have shown that proteins produced by inflammatory cells are the 'smoking gun' behind prostate cancer metastasis. The next step is to completely indict one of them."

Research team member Steven L. Gonias, MD, PhD, added, "This study helps explain the paradox that, in certain types of malignancy, inflammation within a cancer may be counterproductive."

A major cause of Prostate Cancer-Bisphenol-A, in everything

MCCLATCHY TRIBUNE
WHAT IT'S IN
Products that might contain bisphenol-A:
• Hard, clear plastic baby bottles
• Hard, clear, sometimes tinted plastic water bottles
• Hard, clear plastic bowls, tableware and storage containers
• Liners inside food and drink cans
• Dental sealant to prevent cavities
• Electronic equipment
• Sports-safety equipment
• Medical devices
• Pet carriers
• Spray-on flame retardants
Source: American Plastics Council
SAFETY TIPS
Polycarbonates can be identified by the recycling No. 7, which often appears with arrows in the shape of a triangle on the bottom of containers. Bottles that show wear, are cracked, or are cloudy should be discarded. Exposing these products to high temperatures should be avoided.
Although its name may not be familiar, bisphenol-A is everywhere. It's in the lining of your soup can, the clear plastic of your baby's bottle and the sealants covering your teeth.
But it might be harmful to your health.
An expert panel of endocrinologists, statisticians and biologists was called together last week by a federal agency to review a report on this ubiquitous chemical. The final review, which was supposed to be announced earlier this month, was postponed.
For several years, scientists have been concerned about bisphenol-A. Hundreds of papers have shown that it can be toxic in extremely low doses.
Traces of bisphenol-A have been found in nearly every American tested for it.
The chemical mimics estrogen and binds to estrogen receptors on cells. In more than 100 experiments conducted on lab animals, it has been shown to cause genetic changes leading to prostate cancer, as well as decreased testosterone, low sperm counts and signs of early female puberty.
Work also has been done on human tissue, with results showing that exposure can cause changes in prostate and breast tissue.
The National Institutes of Health's Center for the Evaluation of Risks to Human Reproduction, which was charged with drafting the report, may be compromised, critics say. The environmental organization Environmental Working Group has evidence showing that a private consulting firm with close ties to the chemical industry did much of the work on this report, as well as for the center itself.
The firm, Sciences International, has had clients including BASF and Dow Chemical — companies that manufacture bisphenol-A — as well as DuPont, Chevron, Exxon Mobil, 3M, Union Carbide, the American Petroleum Institute and the American Chemistry Council.
Since allegations were made public earlier this month, Sciences International has been removed from the review. But questions remain about its role within the federal center and in the report it compiled for the expert panel's review.
However, the reason for the delay in the expert panel's conclusions was not any association with Sciences International, said Allen Dearry, the interim associate director of the NIH's National Toxicology Program, which is also associated with the reproductive-health center.
The delay, he said, is the result of the enormous volume of material required for the panel to review.
"They are reviewing 600 studies," said Christine Bruske-Flowers, spokeswoman for the federal National Institutes of Environmental Health Science, which is also involved with the center. "They haven't been able to get through them all."
The panel will reconvene in two or three months, officials said.
Sciences International referred all questions to the center.
Bisphenol-A is the raw material of polycarbonate plastic and epoxy resins. Plastic manufacturers value this polymer for its ability to withstand high temperatures, its durability and its transparency. It is because of these characteristics that manufacturers use it for making drinking vessels such as water and baby bottles.
Epoxy resins are used on the inside of tin and aluminum cans to prevent corrosion.
According to Rudolph Deanin, a professor of plastics engineering at the University of Massachusetts-Lowell, bisphenol-A will leach from polycarbonate if exposed to hot liquids or alkaline material.
Other studies have suggested it can leach into water at lower temperatures.
The chemical has been highly controversial. Industry groups have claimed that human exposure levels are too low to cause harm. Indeed, they have provided about a dozen of their own studies to support this contention.
But researchers, including Patricia Hunt, a reproductive biologist at Washington State University, beg to differ.
Hunt became interested in bisphenol-A research after all of her laboratory mice started showing high levels of genetic abnormalities in 2003. She discovered the animals had been exposed to bisphenol-A that was leaching from their polycarbonate cages — and it was this chemical that had caused the abnormalities.
Since then, she has conducted experiments showing that at low doses, the chemical can cause problems. In a recent study, she demonstrated that bisphenol-A, when exposed to pregnant female mice, affected not only the pregnant mice, but the egg production of the female pups.
That's an effect that spans three generations — the pregnant mouse, the fetal mouse and the eggs of the fetal mouse.
"I fell into this by accident," she said. "But I'm pretty committed because I'm horrified by what I see."
Hunt said the chemical is more likely to leach as the product ages. Bottles that show wear or are cracked or cloudy should be discarded. And exposing these products to high temperatures should be avoided.
Polycarbonates can be identified by the recycling No. 7, which often appears with arrows in the shape of a triangle at the bottom of a bottle or container. Baby-bottle manufacturers are not required to label their bottles.
"I'm trying to walk a fine line," Hunt said, "between making consumers aware and freaking parents out and making them unable to sleep at night."
But she's concerned enough that she now stores her food in glass containers and never microwaves plastic.
WHAT IT'S IN
Products that might contain bisphenol-A:
• Hard, clear plastic baby bottles
• Hard, clear, sometimes tinted plastic water bottles
• Hard, clear plastic bowls, tableware and storage containers
• Liners inside food and drink cans
• Dental sealant to prevent cavities
• Electronic equipment
• Sports-safety equipment
• Medical devices
• Pet carriers
• Spray-on flame retardants
Source: American Plastics Council
SAFETY TIPS
Polycarbonates can be identified by the recycling No. 7, which often appears with arrows in the shape of a triangle on the bottom of containers. Bottles that show wear, are cracked, or are cloudy should be discarded. Exposing these products to high temperatures should be avoided.