Men’s Health

While the title of this section is Men’s Health, we’re focusing on prostate cancer since it is the third most common cause of cancer death in American men and the most common cause of death from cancer in men over 75 years old. It affects one in eight American men — one every three minutes — making it the most commonly detected malignancy in men today.
     One reason behind the deadly nature of prostate cancer is that there are usually no symptoms until the cancer is advanced, and it’s too late to treat. Another reason may have to do with the nature of one of the diagnostic tests for prostate problems — the digital rectal exam.
     Depending on a man’s risk factors, a yearly prostate exam should start at age 40 or 50. Age, race and ethnicity all play a role in prostate cancer risk. For example, at age 50, almost 33 percent of men have small prostate tumors. By age 80, about 75 percent are believed to have prostate cancer. African-American men are twice as likely to develop prostate cancer while Asians have the lowest incidence. White males fall in between. Also, high levels of testosterone are associated with an increased risk of prostate cancer.
     Lab tests such at the total PSA (prostate specific antigen) and free PSA can make a big difference in the number of men who are diagnosed early enough to receive treatment. Unfortunately, PSA screening is not yet a medically-accepted standard like mammography and Pap smears for women. In our conversation with Dr. William Catalona on page 29, he points out some of the controversies surrounding screeing and explains why he believes there should be more prostate cancer testing instead of less.
     On a more optimistic note, we found numerous studies indicating that men who eat a low-fat, high-fiber diet replete with cruciferous vegetables can decrease their risk of prostate cancer.
     With automated PSA testing just around the corner, it won’t be long before prostate screening becomes a medically accepted practice we can all agree on.

Vegetable intake lowers prostate cancer risk   
A team of Seattle researchers has found that vegetable intake, particularly that of cruciferous vegetables including broccoli, cauliflower and Brussels sprouts, can substantially lower the risk of prostate cancer.
     Alan R. Kristal, M.D., a member of the Fred Hutchinson Cancer Research Center, Seattle and professor of Epidemiology at the University of Washington, has been studying the effects of diet on prostate cancer for more than five years. Kristal and his colleagues studied 628 men, aged 40 to 64, newly diagnosed with prostate cancer, and 602 cancer-free men the same age. The men were asked about their consumption of 99 food items during a three to five year period.
     Kristal’s team found that men who ate 28 or more servings of vegetables per week had a 35 percent lower risk of prostate cancer compared to men who consumed fewer than 14 servings of vegetables per week. Additionally, men who ate three or more servings of cruciferous vegetables per week had a 42 percent decreased risk of prostate cancer over men who ate less than one serving per week.
     “Our study is the only large study to look at relatively young men and by that I mean under 65. Prostate cancer is rare in men under 65,” Kristal said.
     Kristal believes research is narrowing in on vegetables and supplements in protecting against cancer. He cited a trial investigating the use of selenium to prevent recurrence of skin cancer where researchers found protection against prostate cancer. Another trial where researchers were looking for protection against lung cancer with Vitamin E found protection against prostate cancer. “These were unexpected, chance findings,” Kristal said. “There is some corroborative evidence of protective effect for Vitamin E and for Zinc, and there are some people who are not finding that.”
     “The reason nutrition is kind of important, is there ain’t nothing else going on out there. It’s a disease where, frankly, the risk factors are being black, being old, being alive and being a man. It looks like diet makes a difference, and that is the one thing men can do to help lower the risk.” Kristal’s study included men who were diagnosed with prostate cancer in King County, Wash., during a three-year period. However, the Seattle area population is less than 10 percent African American, a high-risk group.
     However, the vegetable findings are controversial for a garden variety of reasons. Some early studies asked only 10 questions about diet. But a mix of studies has found that tomatoes, green leafy vegetables, other greens, cruciferous vegetables and lots of vegetables can lower the risk of prostate cancer. “It’s beginning to look like more than 50 percent of people are finding something for vegetables,” Kristal said.
     Cruciferous vegetables, in particular, are high in substances called isothiocyanates, which activate enzymes that detoxify carcinogens. Vegetables evolved mechanisms such as cytochemicals to avoid being eaten while humans evolved the ability to detoxify these cytochemicals.
     “The human enzyme system that we use to detoxify cytochemicals are the same enzymes that detoxify naturally occurring carcinogens. Upregulating these enzyme systems gives a protective effect,” Kristal said.
     Kristal, a culinary school graduate and former chef, studied nutrition before he went into epidemiology and research. “I don’t think men listen to health messages until it has to do with their prostate,” Kristal said.
     A few years ago, Kristal took part in diet change intervention trials with women on very low fat diets for a number of years. The investigators also studied the women’s husbands to learn if they adopted any of the dietary moderations. “We found they did eat lower fat diets, but it was because of the foods they were served,” Kristal said. “There is some message here about men not taking responsibility for the food that’s on their plate.”
     Risking the ire of the nutrition community, Kristal recommends a little bit of fat to flavor vegetables. “If that’s the way you like to eat vegetables, great, do it,” Kristal said. “I’m not saying put gallons of Hollandaise on your broccoli, but eating vegetables doesn’t mean you have to eat steamed vegetables with no salt and no butter.”
– Melissa R. Mac

Natural substance found in wine, tea and onions relieves chronic prostatitis pain
According to a study published in a recent issue of Urology, more than 80 percent of chronic prostatitis patients who took a proprietary formulation of quercetin experienced significantly reduced pain and improved their quality of life. Quercetin is a natural dietary substance, known as a bioflavanoid, found in red wine, green tea and onions. According to the Institute for Male Urology, of Encino, Calif., it has been clinically shown to have antioxidant, anti-inflammatory and antimicrobial properties.
     The random, double-blind, placebo-controlled study was conducted by researchers at the institute, who found that 82 percent of patients who received Prosta-Q, a specially formulated blend of quercetin, recorded at least a 25 percent improvement on a national pain and quality of life symptom score. Lead researcher Daniel A. Shoskes, M.D., a renal transplant specialist and associate professor of urology at the UCLA School of Medicine, said the findings offer hope to millions of men who suffer from prostatitis. Shoskes said the study provides a new option for doctors who have been frustrated by limited treatment choices. Before this study, the men involved had failed multiple courses of antibiotics and other therapies.
     Nonbacterial chronic prostatitis is an inflammation of the prostate gland. Its primary symptom is chronic urogenital pain. It effects an estimated 30 million American men, and according to Shoskes, nonbacterial chronic prostatitis is one of the most common reasons men visit urologists. Shoskes said nonbacterial chronic prostatitis is one of the most discouraging conditions doctors face because often there is little that can be done to alleviate the pain.

Test measures the heart’s response to anger and stress and may identify heart attack risk
Researchers at the Henry Ford Hospital in Detroit report that a test measuring the heart’s response to anger and mental stress may help identify people who are at risk of having a heart attack.
     Investigators found that patients who reported higher levels of irritability or anger in response to a mental stress test were more likely to exhibit ischemia, a lack of blood flow to the heart, that can indicate an increased risk of heart attack.
The study’s lead author, Mark Ketterer, Ph.D., of the hospital’s department of Behavioral Health, said researchers have known that most episodes of ischemia do not occur when people are exercising. The likely suspect is mental stress since people spend more of their time stressed mentally rather than physically. The findings, published in the January issue of the Journal of Health Psychology, suggest that anger should be thought of as a risk factor for heart disease, Ketterer said.
     The study of 160 men and 24 women, who had heart disease or a heart attack, measured the heart’s physiological response to mental stress. Participants took treadmill stress tests to measure their baseline level of ischemia, and later, underwent two five-minute mental stress tests. In one test, subjects participated in a confrontational role-playing game. In the other, they played a computerized word game that challenged participants to select color words that appeared in the wrong color.
     At one-minute intervals during the test, heart rate and blood pressure were automatically recorded. Blood was drawn periodically to gauge hormonal levels. In addition, the heart was imaged to determine the amount of blood pumped and the motion of the heart wall.
     Those who reported high levels of anger or irritability during the role-playing were more likely to have ischemia during the test. This was seen primarily in the women in the study, according to the report. The results do not necessarily mean that men do not get as angry as women, but that men may be less likely to admit that they are angry. Researchers also found that anger provoked an ischemic response 58 percent of the time and that patients with ischemia displayed more anger and irritability than those who did not have ischemia. Consistent with previous observations that heart attacks are more likely to occur during a stressful interpersonal confrontation, patients elicited a more intense physiological response to the role-playing than to the color-word task. Participants who were reward-dependent, eager to please others or sensitive to social situations were more likely to display ischemia in stressful interpersonal situations than those who were detached and insensitive.
     Teaching people how to control their anger may help reduce the risk of heart attack. He noted that antidepressant and antianxiety medication could help individuals avoid losing their temper.

Docs differ on role of prostate screening
Prostate cancer screening is controversial. On one side are some general practitioners and internists who see the screening test as imperfect. On the other hand are radiation and medical oncologists and urologists like William Catalona, M.D., of the Washington University School of Medicine in St. Louis. Dr. Catalona is a passionate advocate of not only PSA (prostate specific antigen) testing, but testing with only FDA-approved assays. His opinions are based on more than 11 years of researching and treating prostate cancer patients.

Q. Why isn’t PSA screening more widespread?
A. The medical community has been divided on the value of prostate cancer screening. For screening to be a generally accepted practice, it really requires an act of Congress, literally. So the only cancers for which screening is approved are cervical, breast and colo-rectal cancer. For people to accept screening for a new disease, you have to prove that it reduces death rates and in general does more good than harm.
    With breast cancer and colo-rectal cancer, that has been done using prospective randomized clinical trials. With cervical cancers, it was hotly debated. What happened was women got Pap smears anyway, and after a few years the death rate from cervical cancer went down. So that kind of settled the issue. But with prostate cancer there is no proof yet that screening does more good than harm.

Q. Are you talking about just lab tests or also the digital rectal exam (DRE)?
A. Either or both. There is part of the medical community — internists, family practitioners and epidemiologists — who take a societal perspective. They say there are a lot of other things we need to spend healthcare dollars on. So before we jump into screening for prostate cancer, we need proof positive that it’s going to do more good than harm. They say we shouldn’t do it until we have real proof that it’s going to be beneficial. They are a very loud voice against screening for prostate cancer, and they basically say the evidence is insufficient.

Q. What’s the harm?
A. The No. 1 harm is the economics because it diverts resources away from other worthwhile things. Also, that the screening causes anxiety because men worry that they might have cancer. If they find out they have cancer, the treatment (surgery, radiation) can cause impotency or incontinence. So that’s the harm. So until we’re sure that this is going to be beneficial, we should not do it.
The people on the other side of the issue, people like myself — urologists, radiation oncologists and medical oncologists-take a different perspective. They would argue that prostate cancer is the most common cancer in men. There is no known way of preventing it. There is no known treatment available or on the horizon for advanced prostate cancer. For most cancers, if you catch them early, treatment is more effective. We have a very good new test for detecting it early, but the studies that they’re asking for to prove that it works will take 15 years. But by that time, half a million men will have died from prostate cancer. We believe we ought to use it now. That’s where the battle lines are drawn.

Q. Is the test you’re referring to the total PSA (prostate specific antigen)?
A. Yes, the total PSA either with or without the free PSA. There are some prospective randomized clinical studies underway, but they are flawed and probably won’t answer the question definitively. What we’re seeing with prostate cancer is the same thing we saw happen with cancer of the cervix in women. People fought about Pap smear screening, and the doctors and the patients did them anyway and the death rate fell. The same thing is happening with PSA testing. It’s very, very widespread despite the fact that people are recommending against it. For the first time in 30 years, prostate cancer deaths are beginning to fall. Last January, there was an article in the Journal of the National Cancer Institute that looked at trends in the National Cancer registry database. It concluded that at least part of the reason for it, no matter how much of a skeptic you are, must be PSA testing. So over the next three to four years, I think we’ll continue to see these trends where prostate cancer deaths are falling and people will agree by consensus that prostate cancer screening is worthwhile.

Q. When you combine the total PSA (tPSA) test with the free PSA (fPSA), isn’t it much more reliable?
A. People who hate PSA testing complain that it’s not 100 percent perfect. One of the things that really bothers them is unnecessary biopsies. But if you look at the same data in women who have a positive mammogram, only 9 to 17 percent of those biopsied have cancer. So most women who have a positive mammogram don’t have breast cancer, yet mammography saves lives. So just because a test isn’t perfect doesn’t mean it can’t save lives.
With PSA testing, using the traditional cut-off of 4, it turns out that only 25 to 35 percent of men have prostate cancer and 60 to 65 percent don’t. So what they say is, you are really frightening all of these men with these false-alarm PSA tests. You’re putting them through all this anxiety and biopsies when most of them don’t have cancer. So it’s not a very good test.

Q. What does free PSA do?
A. The main purpose of the free PSA test is to eliminate unnecessary biopsies. If a man has a total PSA higher than 10, there’s about a 60 percent chance he has prostate cancer. If a man has a tPSA lower than 2 or 2.5, there’s almost no chance he’ll have cancer if you biopsy him. The gray zone is a tPSA of between 2.5 and 10. Globally, if you took a group of men who had tPSAs between 2.5 and 10, about 25 percent would have cancer. Here’s where the fPSA test comes in. If you had two men who had a PSA of 4. They were the same age, race and everything. One of them has a percentage of fPSA greater than 25 percent so if his tPSA score of 4 nanograms, one nanogram is fPSA. Then his chance of having a positive biopsy is 8 percent or 1 out of 12. You can tell that man, you do have a tPSA of 4, but if we put you through a biopsy there’s only 1 chance in 12 that they will find cancer.
    Now if you take his counterpart, who’s alike in every other way, and his fPSA is less than 8 percent. If he has a biopsy, the chances of cancer are 60 percent. So it allows you to give a more accurate risk assessment of whether the biopsy is going to show cancer.

Q. So it helps rule out both false negatives and false positives?
A. If you use a cutoff of 25 percent fPSA, you can detect 95 percent of the detectable cancers and you can eliminate 20 percent of the unnecessary biopsies. We’ve also recently published in JAMA that the fPSA test also works in the 2.5 to 4 range of TPSA.
     If a man who had prostate cancer has a tPSA of 3, but his fPSA was low, it would be considered a false negative, because your 4 cutoff missed that. But if you use the fPSA in that range, you’ll pick up his low fPSA and eliminate a false negative. So it has the capability of eliminating both false positives and false negatives and making the tPSA test more accurate.
     It should be given in the 4 to 10 range, and I really think it should be given to anyone with a tPSA in the 2.5 to 10 range to make the best use of it. The study done for FDA was based on men with a Total PSA of 4 to 10. The study on the 2.5 was done at a later time, and the company hasn’t yet submitted it to the FDA, but it does work in that range. The use of fPSA in the 4 to 10 range reduces false positives and eliminates unnecessary biopsies.

Exercise may increase testicular cancer risk
Two Canadian researchers at the University of Toronto, Ontario, have reported that teenage boys who exercise regularly and men in their 20s with physically demanding jobs may be more likely to develop testicular cancer than less active men.
     Dr. Nancy Kreiger and Anil Srivastava, now an M.D. student at Queen’s University, Kingston, Ontario, compared data on 212 men with testicular cancer and 251 men without it. The 20- to 74-year old men filled out questionnaires on their frequency of moderate or strenuous exercise during different life periods. In the study, moderate exercise referred to brisk walking or gardening, and strenuous exercise was any exercise lasting at least 20 minutes.
     “We looked at both moderate and strenuous exercise, nothing explicitly defined,” Srivastava said. “What we found for both moderate and strenuous activity in the range of something between three to more than five times a week, was an adverse association with physical activity. It was particularly strong for more than five times a week.”
     Their findings, reported in the January issue of the American Journal of Epidemiology, found that the more frequently teenagers exercised, the greater their risk of testicular cancer. The researchers also reported that men who had moderate or strenuous job demands in their twenties had approximately a 70 percent to 85 percent increased risk of testicular cancer, compared to men who did not work at such jobs during their twenties. Srivastava said the study did not ask participants about specific types of occupational activity, but relied more on what the subject’s perception of their own occupational exertion. Kreiger and Srivastava originally speculated that physical activity would lower the risk of testicular cancer. Exactly how physical exercise may increase the risk of testicular cancer is not known, although the investigators suggested physical activity during the teenage years possibly delays puberty in boys, which may cause changes in male hormone levels, and somehow increase the risk of cancer.
     It is possible, according to Srivastava, that cumulative exposure to sex hormones may result in an increase in the risk of cancer, but if puberty is delayed, then there is simply less cumulative exposure. “With physical activity you generally see a reduction in the onset age of puberty,” Srivastava said. “With females it is more easy to define. With males it is not quite so easy.”
     What may be more relevant, Srivastava said, are the transient increases in sex hormone levels while exercising. Some people find that after extended exercise there is a large increase in testosterone levels. “Unfortunately the results are inconsistent. We are hesitant to expand on our findings because there is that inconsistency about sex hormones and physical activity,” Srivastava said. He would like to see their study replicated and more research done at the biological level.
     “Should we say that physical activity should be curtailed? I suppose we skirted somewhat in our article,” Srivastava said. “Obviously there are other risk factors to consider before assuming that physical activity is adversely associated with testicular cancer. One would have to consider those before making any sort of public health recommendations.”
– Melissa R. Mac