A man's height is a modest marker for risk of prostate cancer development, but is more strongly linked to progression of the cancer, say Bristol researchers who conducted their own study on the connection and also reviewed 58 published studies.
In the September issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, 12 researchers at four universities in England studied more than 9,000 men with and without prostate cancer and estimated that the risk of developing the disease rises by about six per cent for every 10 centimeters (3.9 inches) in height a man is over the shortest group of men in the study. That means a man who is one foot taller than the shortest person in the study would have a 19 per cent increased risk of developing the disease.
Still, these increases in risk are a lot less than those linked with other established risk factors, such as age, family history of the disease, and race. Because of that, the researchers do not suggest that taller men be screened more often than is typical, or that their cancer treatment be altered.
"Compared to other risk factors, the magnitude of the additional risk of being taller is small, and we do not believe that it should interfere with preventive or clinical decisions in managing prostate cancer," said the study's lead author, Luisa Zuccolo of the Department of Social Medicine at the University of Bristol. "But the insight arising from this research is of great scientific interest. Little is known on the causes of prostate cancer and this association with height has opened up a new line of scientific inquiry."
For example, Zuccolo says that factors associated with height - not height itself - could be risk factors for progression to fatal prostate cancer, and a plausible mechanism behind this association could be the insulin-like growth factor-1(IGF-1) system, which stimulates cell growth and has been shown to be involved in prostate cancer incidence and progression.
Because some studies have shown a much greater association between height and prostate cancer risk - some between 20 to 40 per cent - the researchers then placed their results in the context of available evidence. They conducted a meta-analysis of 58 studies, and found evidence that greater stature is associated with increased prostate cancer risk. But as in their study, the overall effect varied with study design and was modest - a three to nine per cent increase risk of development per 10 centimeters, and five to 19 per cent increase in risk for more advanced cancer.
"We do not believe that height itself matters in determining risk of prostate cancer or prostate cancer progression, but we speculate that factors that influence height may also influence cancer and height is therefore acting as a marker for the causal factors," Zuccolo said.
Paper:
'Height and Prostate Cancer Risk: A Large Nested Case-Control Study (ProtecT) and Meta-analysis' by Luisa Zuccolo, Ross Harris, David Gunnell, Steven Oliver, Jane Athene Lane, Michael Davis, Jenny Donovan, David Neal, Freddie Hamdy, Rebecca Beynon, Jelena Savovic, and Richard Michael Martin. Cancer Epidemiol Biomarkers Prev 2008;17(9). September 2008
We do not believe that height itself matters in determining risk of prostate cancer or prostate cancer progression, but we speculate that factors that influence height may also influence cancer and height is therefore acting as a marker for the causal factors.
http://www.epi.bris.ac.uk/
Cialis may help men with benign prostatic hyperplasia symptoms
Posted by Hamberu Labels: Men's Health NewsBenign prostatic hyperplasia (BPH) can be helped with a daily dose of erectile dysfunction drug tadalafil (Cialis) to relieve associated lower urinary tract symptoms (LUTS), according to a new study published in the October 2008 issue of The Journal of Urology.
Researchers from the University of Texas Southwestern Medical Center at Dallas, Northwestern University and Lilly Research Laboratories report on a randomized, double-blind, placebo-controlled study of over 1000 men in ten countries.
Claus G. Roehrborn, MD, Professor of Urology, University of Texas Southwestern Medical Center, states, "Since reports of erectile dysfunction (ED) incidence, pathophysiology and treatment have shown a possible link between BPH LUTS and ED. PDE5 inhibitors like tadalafil (Cialis) have received increased attention for treating BPH LUTS, although they are currently only approved for ED. The half-life of tadalafil is 17.5 hours, making it suitable as once daily therapy. Although the precise mechanism of action by which PDE5 inhibitors may alleviate LUTS is not completely understood, several putative mechanisms are currently under investigation."
Men with signs of BPH may experience LUTS, such as urinary frequency, urgency, intermittence, nocturia, straining, incomplete emptying or a weak urinary stream. LUTS increase with age with an overall prevalence of greater than 50% in men 50 years or older. Drugs currently used to treat these symptoms can produce unwanted side effects, including dizziness, low blood pressure and sexual dysfunction.
Participants in the tadalafil study were required to have at least a 6-month history of LUTS secondary to BPH. Subjects with a high PSA (more than 10 ng/ml) were excluded, as were subjects with other complicating conditions or conflicting drug treatments. Anyone who had undergone treatment for erectile dysfunction or other BPH treatments underwent a 4-week treatment-free screening period. All participants then received placebo for 4 weeks prior to randomization. The 1056 subjects were then divided randomly into 5 groups that received a placebo, or doses of 2.5, 5.0, 10.0 or 20.0 mg/day of tadalafil.
Using the International Prostate Symptom Score (I-PSS), a validated seven-item questionnaire about LUTS occurring within the last month, the researchers found that all doses of tadalafil were superior to placebo for relieving LUTS, with statistically significant effects at 4, 8 and 12 weeks. The treatments decreased I-PSS scores from 3.9 to 5.2 points in the different dosage groups, a clinically meaningful improvement according to the guidelines of the American Urological Association. Of the doses studied, 5 mg per day improved the I-PSS by 4.9 points and provided the best risk-benefit profile.
http://www.jurology.com/
Brachytherapy may benefit obese prostate cancer patients
Posted by Hamberu Labels: Men's Health NewsBrachytherapy, also called seed implants, may be a more beneficial treatment than surgery or external beam radiation therapy for overweight or obese prostate cancer patients, according to a study published in the August issue of the International Journal of Radiation Oncology-Biology-Physics, the official journal of the American Society for Therapeutic Radiology and Oncology.
"Brachytherapy may be the preferable treatment for obese men with early-stage prostate cancer," Anthony Zietman, M.D., one of the authors of the study and a radiation oncologist at Massachusetts General Hospital in Boston, said. "Being overweight does not present any unique technical challenges for brachytherapy as it does for surgery and external beam."
There has been some evidence published suggesting that men with a high body mass index have a greater likelihood of PSA failure after some prostate cancer treatments than normal-weight men. This has been specifically shown for overweight or obese men who undergo surgery (radical prostatectomy) or external beam radiation therapy. The exact cause for this is unknown but it is suspected that higher BMI can been associated with more aggressive cancers and also with more technical difficulties during treatments.
Researchers at the Massachusetts General Hospital departments of radiation oncology and urology and the Boston Medical Center Department of Radiation Oncology, both in Boston, sought to determine if the same problems were seen in overweight and obese men treated with brachytherapy.
The study analyzed 374 prostate cancer patients who were treated with brachytherapy from 1996 to 2001, and researchers found that the six-year PSA failure rate for men who were overweight or obese was no higher than for those of normal weight.
http://www.astro.org/
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Health risk behaviors such as smoking and obesity associated with lower prostate specific antigen awareness
Posted by Hamberu Labels: Men's Health NewsAccording to a study conducted at Columbia University Mailman School of Public Health, health risk behaviors such as smoking and obesity are associated with lower awareness of the Prostate Specific Antigen (PSA), which could lead to a lower likelihood of undergoing actual prostate cancer screening.
Although previous studies have explored predictors of PSA test awareness, this is the first research to focus on health risk behaviors, such as smoking, physical inactivity, obesity, and excessive alcohol consumption. The study findings were reported in the August issue of The Journal of Urology.
Awareness of PSA testing is considered an important cognitive precursor of prostate cancer screening and it was found to contribute to differences in prostate cancer screening rates. Earlier studies have suggested that persons who seek out cancer information are more likely to acquire knowledge, demonstrate healthy behaviors, and undergo cancer screening. According to the Mailman School study, a quarter of the men older than 50 years without a history of prostate cancer who were among the population of 7,000 men studied, remain unaware of the PSA test.
"Our primary findings suggested that smoking, physical inactivity and obesity are inversely associated with awareness of the PSA test. These risk behaviors are linked with higher prostate cancer morbidity and mortality," said Firas S. Ahmed, MD, MPH, Mailman School of Public Health, and first author. This finding may be due to a general lack of concern about health maintenance or less interactions with health care providers by smokers, according to Dr. Ahmed.
The earlier research also indicated that patients with prostate cancer who smoke present a worse prognosis than patients who do not smoke, and that obesity is associated with more advanced stages and higher grades of prostate cancer.
"The results concur with our initial hypothesis that men who adopt unhealthy lifestyles may be less concerned with health and less aware of preventive measures like the PSA test," says Luisa N. Borrell, DDS, PhD, adjunct assistant professor in the Mailman School of Public Health's Department of Epidemiology, and senior author. Given the associations between smoking, physical inactivity, and obesity with prostate cancer and cardiovascular disease, men with multiple risk behaviors would seem to be ideal targets for interventions to improve their awareness of the PSA test, the authors note.
http://www.mailman.hs.columbia.edu/
Read More......Young type-2 diabetic men suffer low testosterone levels
Posted by Hamberu Labels: Men's Health NewsYoung men with type 2 diabetes have significantly low levels of testosterone, endocrinologists at the University at Buffalo have found -- a condition that could have a critical effect on their quality of life and on their ability to father children.
This study follows research published earlier by these scientists reporting that one-third of middle-aged men with type 2 diabetes have low testosterone levels, requiring treatment for erectile dysfunction.
"These new findings have several clinical implications besides the impairment of sexual function in these young men," said Paresh Dandona, Ph.D., UB Distinguished Professor in the Department of Medicine and senior author on both studies.
"The lack of testosterone during these critical years may lead to diminished bone mass and the lack of development or lose of skeletal muscle. In addition, these patients may gain more weight (with an average body mass index of 38 they already were obese) and become more insulin resistant.
"Also, patients with low testosterone and type 2 diabetes have been shown to have very high concentrations of C reactive protein," he added, "which increases their risk of developing atherosclerosis and heart disease above and beyond the risk associated with diabetes."
Results of the new study appear in the online edition of Diabetes Care and will be published in an upcoming edition of the journal.
Anil Chandel, M.D., UB clinical assistant instructor and medical resident working with Dandona, is first author.
The current study was conducted in 38 men with type 1 diabetes and 24 men with type 2 diabetes who were referred to the Diabetes-Endocrinology Clinic of Western New York at Millard Fillmore Hospital of Kaleida Health, where Dandona is chief of the Division of Endocrinology.
The average age of men in the type 1 and type 2 groups was 26 and 27, respectively, with a range of 18-35 years.
Results showed that type 2 diabetics had half the amount of total and free testosterone in their blood as their type 1 counterparts. Free testosterone is the amount of the hormone not bound by protein molecules that can affect bodily functions.
Using the amount of free testosterone considered normal in men in general, eight out of the 24 type 2 diabetics had below-normal concentrations. However, using the normal range for men of their age, 14 out of the 24, or 58 percent of the young type 2 diabetics had lower than normal testosterone levels. Type 1 diabetics, meanwhile, had normal levels of total and free testosterone for their age group.
Patients with below-normal testosterone also had low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are released by the pituitary gland and are essential for testosterone secretion and normal fertility. Low levels of all three hormones results in a syndrome known as hypogonadotropic hypogonadism.
"While obesity contributes to the association of type 2 diabetes and hypogonadotropic hypogonadism (HH), the association is not dependent entirely on obesity," said Dandona. "In our first study of diabetic men, we found that 31 percent of lean type 2 diabetics also had HH, so it is likely that factors other than obesity contribute to HH, possibly insulin resistance. Type 2 diabetic patients generally have higher insulin resistance, while all obese men are not insulin resistant.
"Whether obesity or insulin resistance is the major determinant of HH has to be addressed in future studies, and the pathogenesis of HH needs to be defined," he said. Dandona's group currently is investigating these questions.
Researchers involved in the study in addition to Dandona and Chandel were Sandeep Dhindsa, M.D.; Shehzad Topiwala, M.D.; and Ajay Chaudhuri, M.D., all members of Dandona's research group.
The study was supported by a grant to Dandona from the National Institutes of health. The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. The School of Medicine and Biomedical Sciences is one of the five schools comprising UB's Academic Health Center. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.
Read More......Some of the drugs given to many men during their fight against prostate cancer can actually spur some cancer cells to grow, researchers have found. The findings were published online this week in a pair of papers in the Proceedings of the National Academy of Sciences.
The results may help explain a phenomenon that has bedeviled patients for decades. Hormone therapy, a common treatment for men with advanced prostate cancer, generally keeps the cancer at bay for a year or two. But then, for reasons scientists have never understood, the treatment fails in patients whose disease has spread - the cancer begins to grow again, at a time when patients have few treatment options left.
The new findings by a team led by Chawnshang Chang, Ph.D., director of the George Whipple Laboratory for Cancer Research at the University of Rochester Medical Center, help explain the process by showing that the androgen receptor, through which male hormones like testosterone work, is much more versatile than previously thought. Under certain conditions the molecule spurs growth, and at other times the molecule squelches growth - just like the same molecule does to hair in different locations on a man's head.
The new findings raise the possibility that under some conditions, some treatments designed to treat prostate cancer could instead remove one of the body's natural brakes on the spread of the disease in the body. The researchers stress that the results are based on laboratory studies and on findings in mice, and it's too soon to know yet whether the findings apply directly to prostate cancer in men.
Understanding the effects of the androgen receptor gives physicians a toehold in efforts to develop more effective treatments for men with prostate cancer. That would be welcome news for the one of every six men who will get the disease during his lifetime. More than 28,000 men die from the disease in the United States each year, according to the American Cancer Society. Men's risk from prostate cancer is about equal to women's risk from breast cancer: Each year, about the same number of men get prostate cancer as women get breast cancer, and their risk of dying from the diseases is about equal, according to ACS.
Chang's findings are most relevant for patients with advanced prostate cancer, who typically receive hormone therapy after other treatments such as surgery or radiation. With hormone therapy, physicians blunt the effects of male hormones like testosterone to bring the disease in the prostate to a halt. One form of hormone therapy works by blocking the androgen receptor. Androgen deprivation therapy is generally very effective for a year or two, but for reasons that no one has understood, the cancer ultimately returns.
"When a man receives hormone therapy, initially the treatment works well, and his PSA (prostate specific antigen) level goes down," said Edward Messing, M.D., a urologist and an author of the paper. "But inevitably, the PSA will start climbing again, and that is usually the first sign that the treatment is beginning to fail. It's a sign that the cancer in the prostate is making a comeback."
In work funded by the National Cancer Institute, Chang's team found that blocking the receptor indeed prevents some cells in the prostate from growing, just as scientists expected. But Chang's team unexpectedly found that blocking the receptor actually spurs other prostate cells to grow.
"The androgen receptor acts differently in different cells in prostate tissue," said Chang. "It's always been assumed that blocking the androgen receptor will stop all prostate cells from growing, but we have found that that's not the case. Since current treatment acts non-specifically on all the cells having androgen receptors in the prostate, blocking the androgen receptor will give mixed results."
The team found that, as expected, the androgen receptor in prostate support cells known as stromal cells stimulates growth of cells, including cancer cells, in the prostate. He also found, surprisingly, that the receptor actually acts as a tumor suppressor in epithelial cells known as basal cells in the prostate.
Then Chang's team knocked out the androgen receptor in specific sets of prostate cells and studied the results. As expected, when the molecule is turned off in stromal cells, growth of cancer cells in the prostate slows. But when the molecule is turned off in the epithelial cells, it removes one of the body's natural inhibitors that prevents prostate cancer cells from spreading, making cells more likely to invade other tissues.
"While the androgen receptor is really driving prostate cancer, in another sense it appears that the receptor also normally inhibits the spread of cancer cells. It seems to have a dual role. Manipulating the androgen receptor can increase or decrease either of these actions depending on precisely how it's done," said Messing.
Chang says the molecule's versatility in the prostate should not come as a surprise, since the molecule's function elsewhere depends on its location.
"The effects of the androgen receptor on hair growth in men vary dramatically depending on where in the body the receptor is working," said Chang. "When the receptor is very active in the mustache area, more hair grows. When it's very active on the top of the skull, toward the front, hair falls out and men become bald. And the hair on the back of the head is insensitive to the receptor. The effects of hormones depend on the location.
"We found that the same is true within the cells of the prostate itself," said Chang, who is a faculty member in the departments of Urology and Pathology and the James P. Wilmot Cancer Center.
Chang says it's likely that the androgen receptor works differently in different cells partly because the assortment of molecular colleagues it works with within the body changes from situation to situation. Like a foreman turning to a pool of employees to get certain jobs done, the androgen receptor taps different molecules in different situations, forming intricate complexes or groupings that then accomplish various tasks. The receptor works very quickly, assembling a team within seconds, accomplishing a task, then disbanding and making its helpers available to form a brand new team for another task.
Chang's team is working on ways to focus on these molecular "co-factors" as a way to target the androgen receptor differently in different cells, for instance, turning off the receptor in some cells while keeping it on in others, to fight prostate cancer. That type of cell-specific targeting is currently not possible.
The research in the laboratory involved tracking the disease in mice and also analyzing human prostate cancer cells in culture. Nevertheless, the work might include some hints for improving patient care. Possibilities include studying whether androgen suppression therapy might be used to target only specific cells within the prostate, as well as checking whether drugs designed to prevent cancer from spreading should be used in concert with hormone therapy.
http://www.urmc.rochester.edu/
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