Category Archives: Prostate Cancer

Are Annual Prostate Cancer Screenings Necessary? Should Early Stage Prostate Cancer Be Treated?

By Krystle Seu, Dana Casciotti, PhD, Brandel France de Bravo, MPH, Mingxin Chen, MHS, and Nicholas Jury, PhD

Prostate cancer is the #1 cancer in men and the second leading cause of cancer deaths for men in the United States, after lung cancer.1 One in every six men will be diagnosed with prostate cancer in his lifetime,2 with about 90% of cases occurring in men 55 and older, and 71% of deaths occurring in men 75 and older.3 For these reasons, annual screenings would seem to be an important way to prevent prostate cancer.  But there is a hot debate within the medical community: do regular prostate cancer screenings do more harm than good?

Should I Get Screened?

Diagnostic tests for prostate cancer are recommended for any man who has symptoms of prostate cancer, such as pain or changes in urination.  Men over the age of 50 who have no symptoms sometimes undergo screening tests.  In May 2012, the U.S. Preventive Services Task Force recommended against prostate-specific antigen (PSA) screening tests for men of any age. However, in May 2018, the Task Force revised their recommendation, stating that men ages 55-69 years old should talk to their doctor about the potential benefits and harms of PSA screening. The USPSTF continues to recommend against PSA screening in men age 70 and older. (seehttps://screeningforprostatecancer.org)

What about other methods of screening, like digital rectal exams, which are usually done together with PSA testing? The Task Force continues to conclude that they tend to do more harm than good.

 

The U.S. Preventive Services Task Force is an independent group of medical professionals that reviews all evidence on preventive health care services.  It adopted its current position after expressing doubts about the value of prostate cancer screening for several years.  In 2009, the Task Force said screening was not recommended for men over 75, but wasn’t sure about its value for men younger than 75.” That same year, the American Urological Association issued new guidelines saying that annual screening was no longer recommended.4 5

The reason why these experts concluded that screening was rarely necessary is that prostate cancer grows very slowly.  Even without treatment, many men with prostate cancer will live with the disease until they eventually die of some other, unrelated cause.

Types of Prostate Cancer Screening: PSA Blood Tests and Digital Rectal Exams

Prostate cancer occurs when cells create small tumors in the prostate gland, which is an important part of the male reproductive system.  Screening can be performed quickly and easily in a physician’s office using two tests: the prostate-specific-antigen (PSA) blood test, and the digital rectal exam (DRE), a manual exam of the prostate area.

Most screening tests are not 100% accurate, but these prostate tests are especially inaccurate.  Most men with a high PSA level (>4ng/mL) do not have prostate cancer (this is known as a false positive), and some men with prostate cancer have a low PSA level (this is called a false negative).  The DRE also results in many false positives and false negatives. Using both screening methods together will miss fewer cancers but also increases the number of false positives, which can lead to more testing (usually biopsies of the prostate) and possibly result in medical complications. A biopsy to determine if there is a cancerous growth in the prostate involves inserting a needle, usually through the rectum, to remove a small sample of prostate tissue.

PSA Velocity

Researchers are also trying to determine if other types of PSA testing might be more accurate in detecting prostate cancer, such as changes in PSA levels when a man has multiple tests over time.  The rate of change of PSA level from one test to the next is known as “PSA velocity.”

One study examined if PSA velocity could improve cancer detection compared to standard PSA and DRE screening tests.6  Because men with high PSA levels and positive DRE results typically undergo prostate biopsies to determine the presence of cancer, this study evaluated if PSA velocity helped detect cancer in men with low PSA and negative DRE results.  Over 5,500 men were included in the study and men with high PSA velocity –almost 1 in 7 men– were biopsied.  However, it did not improve cancer detection.

What Recent Research Tells Us About Prostate Cancer Screening

Depending on how often screening is done, it may help reduce the chances of dying of prostate cancer, but the research indicates that the vast majority men with prostate cancer die of a different cause, even if they are not treated.

Two major research studies have tried to shed light on the value of regular screening:  the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Trial of Screening for Prostate Cancer. 7   The PLCO studied 76,000 men, aged 55-74, for 7-10 years and found that the death rate from prostate cancer was low, and that it did not differ between the men who were screened every year for the first six years of the study and those who received their usual care (which ranged from no screening to occasional screening).8 For most of the patients, “usual care” included at least one screening during the first seven years of the study.  There were also no significant differences in overall death rates between the groups.  Although the randomized portion of the study was completed in 2006, researchers are still studying the patients to see how long they live9.

The European study (ERSPC) included 182,000 men, ranging from 50 to 74 years old, from seven different European countries. 10  In these countries, “regular screening” is usually every 4 years, although it is every 2 years in Sweden.  Those men were compared to men of the same age who did not get any prostate cancer screening.  After the men were studied for an average of 13 years, the researchers found that the patients who had PSA screening were 27% less likely to die of prostate cancer. 11  However, they did not live longer than the other men, because they died of other causes.

Recent updates to a 2010 meta-analysis (which means researchers combined data from several different but comparable studies) of six randomized, controlled prostate cancer screening trials (including the PLCO and ERSPC studies) further support the U.S. Preventive Services Task Force recommendations. Analysis of data on almost 330,000 men showed that men who were screened did not live longer than men who were not screened.12

A United Kingdom study published in 2018 in the prestigious medical  journal JAMA involved over 160, 000 men between the ages of 50 to 59 years. The study found that a one-time PSA screen increased the chances of diagnosing prostate cancer, but did not change the chances of dying from prostate cancer. Over a 10-year period, about 4.3% of men who had a one-time PSA test were diagnosed with prostate cancer compared to about 3.6% of men who did not have a PSA screen. The one-time PSA screen was able to detect prostate cancers that were lower grade and less likely to be dangerous.

Importantly, there was no evidence that having a PSA screen test saved lives. In men who were diagnosed with prostate cancer, the chances of dying from the prostate cancer within 10-years of diagnosis were about 3 in 10,000 (less than half of a percent), and that was the case whether the men had a PSA screening or not. This means that a PSA may detect more prostate cancers, but these are likely cancers that would not have been harmful. The study does not show that one-time screening with PSA would be helpful, and it could be harmful. The researchers have planned to look at these issues more closely in a longer term study.13

Benefits and Harms of Screening

The benefit of screening is that the disease is often curable with early detection (90% or better).  Common treatments like surgery or radiation aim to remove or kill all cancerous cells in the prostate.  If the cancer spreads beyond the prostate before it is treated, it is often fatal.  However, the cancer usually grows so slowly that is often equally safe to wait until there are symptoms before attempting to diagnose prostate cancer.  Symptoms of prostate cancer might include urinary problems, difficulty having an erection, or blood in the urine or semen.

The harms of screening include 1) inaccurate results leading to unnecessary biopsies and complications, and 2) complications from unnecessary treatment. Even if a man has prostate cancer, if he does not have symptoms he may not need to be treated.  Experts estimate that between 18% and 85% of prostate cancers detected by these screening tests would never become advanced enough to harm the patient.  This wide range of uncertainty, however (is it less than 1 out of 5 or more than 4 out of 5?) just adds to the confusion.

Unnecessary treatment costs a lot of money, but the main concern is the lack of evidence that it saves lives, on average, and the high rate of complications, which include serious and long-lasting problems, such as urinary incontinence and impotence.14

Long before the Task Force made its recommendation, many doctors and patients questioned whether annual prostate cancer screenings were a good idea, since the disease is rarely fatal. Many also question whether treating early prostate cancer, the kind of prostate cancer screening tests mostly find, is a good idea. Treating early prostate cancer does not appear to help men live longer, and for many it drastically reduces their quality of life.

Doctors and scientists are searching for better tests for prostate cancer detection. Many experts believe that a family history of prostate cancer or other cancers should influence how often a man chooses to get PSA screening.  However, the studies described below, which led to the Task Force’s recommendation against PSA screening, suggest that annual screenings for all men are not a good idea.

Is Surgery Effective for Men with Early-Stage Prostate Cancer?

When they hear the word “cancer,” many men want it treated immediately no matter how slow it is growing or how unlikely it is to be fatal.  The question is: if found in its early stages, should prostate cancer be treated?

In July 2012, a study by researchers at the Department of Veterans Affairs was published in the New England Journal of Medicine, examining the effectiveness of surgery in men with early-stage prostate cancer.15 Known as the Prostate Cancer Intervention versus Observation Trial, or PIVOT, the study compared surgical removal of the prostate with no prostate cancer treatment. The 731 men who participated in the study, with an average age of 67, were randomly assigned to one of the two groups and followed for 8 to 15 years. All the men were enrolled between 1994 and 2002, with a final check-up taking place in 2010. Men in both groups went to the doctor every six months during the study, and men in the observation-only group were offered palliative therapy (which focuses on reducing suffering) or chemotherapy to relieve symptoms due to the cancer spreading to other parts of the body. Neither therapy can eliminate the cancer and, therefore, are not treatments.

The findings suggest that prostate cancer surgery does not save the lives of men with early-stage prostate cancer. Only 7% of the participants died of prostate cancer or from treatment during the study: 21 or 5.8% of those had their prostate removed and 31 (8.4%) who did not undergo surgery. The difference between the surgery and observation groups was not statistically significant, which means that the smaller number who died in the surgery group could have been due to chance. The prostate cancer spread to the bone in 4.7% of the surgery patients and to 10.6% of the observation or no-treatment group. Even when cause of death wasn’t limited to prostate cancer, the two groups died at about the same rate: 47% of the men who had surgery died during the study period as compared with 50% in the observation group.

The only men who benefited from the surgery were those with a PSA of 10 ng per milliliter or higher and men with riskier tumors: their overall risk of dying during the study period-not necessarily from prostate cancer-was lower than in the observation group.  Surgery reduced the risk of dying from any cause by 13.2% among men with a PSA of 10 ng per milliliter or higher. For men with intermediate risk tumors (determined by a PSA value of 10.1 to 20.0 ng per milliliter, a score of 7 on the Gleason scale, or a stage T2b tumor), surgery reduced their risk of dying by 12.6%, but for men with high risk tumors, the reduction in risk by 6.7% was not statistically significant. That means it could have happened by chance.

In September 2016, the prestigious New England Journal of Medicine published a 10-year study by researchers from University of Oxford, which provided solid evidence that neither surgery nor radiation treatments save lives.16 The study compared the death rates of three patient groups: surgery, radiation, and active monitoring. Between 1999 and 2009, the study randomly assigned 1643 men with diagnosed prostate cancer to the three groups to receive radical surgery (553 men), radical radiotherapy (545), or active monitoring (545). Unlike the PIVOT study, patients in the “active monitoring group” underwent tests to determine if their prostate cancer had progressed; these were conducted every 3 months for the first year, and every 6 to 12 months after that. The patients had an average (median) of 10 years of follow-up.

At the final check-up, 169 men had died, and there was no significant difference among the three groups of prostate cancer patients. Only 17 of these were deaths from prostate cancer: 5 in the surgery group, 4 in the radiotherapy group, and 8 in the active-monitoring group. However, prostate cancer was more likely to progress or spread in the group of men who were monitored rather than treated.

This study was the first to compare the effectiveness of surgery, radiotherapy and active monitoring. The findings suggest that treatment does not improve the chances of a man living longer, since most of the men will be dying of other causes rather than prostate cancer. Since prostate cancer treatment can cause serious side effects such as erectile dysfunction and incontinence, active monitoring seems to be a reasonable option.

Can Aspirin Prevent Cancer and Cancer Deaths?

Nyedra W. Booker, PharmD, Tracy Rupp, PharmD, MPH, RD, Laura Gottschalk, PhD, and Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Doctors have prescribed aspirin to prevent heart attacks and stroke for many years. There is now good evidence that regular aspirin use can also prevent cancer. Experts already recommend an aspirin a day to prevent colon cancer, but aspirin may also “play a strong role in reducing death from cancer.”[1]  

Recommending Aspirin for Cancer Prevention

The U.S. Preventative Service Task Force (USPSTF), an independent group of medical experts, recommend  that people between the ages of 50 and 59 should take 81 mg of aspirin daily (which is the typical dosage of “baby” or low-dose aspirin) to prevent colon cancer. Since colon cancer develops slowly overtime, aspirin should be taken for at least 10 years.[2]

Daily aspirin is not for everyone between 50 and 59, however. For example, if you have an increased risk of bleeding because of other medication you are taking or because of a history of stomach or intestinal ulcers, kidney disease, or severe liver disease, the risks of taking aspirin daily may outweigh the benefits. 

The benefits of aspirin in preventing death from cancer are based in part on a 2016 study published in the prestigious Journal of the American Medical Association (JAMA), which looked at the rate of cancer in two large long-term studies.  The Nurse’s Health Study and the Health Professionals Follow-up study included almost 48,000 men and more than 88,000 women.[3] The study found that people who took aspirin regularly had a slightly lower risk for overall cancer and a 19% lower risk for colon cancer. These benefits were seen after just five years of use and are statistically significant, which means they are almost definitely due to the aspirin and not to other factors.

The new study results were presented at a national cancer conference in April 2017 and go beyond the results published in 2016.[1] Women in the studies who took aspirin regularly had a 7% lower chance of dying of any cause than women who did not take regular aspirin. Men who took aspirin regularly had an 11% lower chance of dying of any cause than men who did not take regular aspirin. Dying from cancer was 7% lower in women and 15% lower in men who regularly took aspirin. Women who regularly took aspirin had an 11% lower risk of dying from breast cancer. Men who regularly took aspirin had a 23% lower risk of dying from prostate cancer.  

Aspirin can have many benefits, but since it also has risks more studies are needed to examine who is most likely to benefit and who is most likely to be harmed. The study was observational, which means that it evaluated the health of people in the “real world,” rather than a randomized clinical trial.  Since it is not possible to know as much about all the health habits and other possible influences of the thousands of people in these huge studies as is possible in a clinical trial, the conclusions are considered less certain.

What You Need to do Before Starting Aspirin Therapy

Remember that aspirin is a drug, and it has risks even at low doses. You should talk about whether taking a daily aspirin is a good idea with your doctor, so that you can discuss:

  • Your medical history and all the medicines you are currently using, whether they are prescription or over-the-counter
  • Any allergies or sensitivities you may have to aspirin
  • Any vitamins or dietary supplements you are currently taking

Aspirin should not be taken with certain other over-the-counter pain medications such as ibuprofen (Motrin and Advil) and naproxen (Aleve) because they can increase the risk of internal bleeding. These medications are called NSAIDS.  Aspiring should also not be taken daily by those who regularly use herbs and nutritional supplements.  Vitamin E, fish oil (omega-3 fatty acids) and what’s known as the “four Gs”– garlic, ginger, gingko, and ginseng– can all increase your risk for bleeding when taken with aspirin and other blood thinners.[4]

If taking aspirin is not a safe option for you, there are other ways to reduce your chance of developing heart disease and cancer, without any side effects!  They include quitting smoking, eating a diet rich in fruits and vegetables, and getting up from your chair or couch regularly rather than sitting for hours without moving around. Walking or other exercising for at least 20-30 minutes each day is also helpful. However, for people at highest risk of heart disease or cancer, aspirin could truly be a lifesaver.

The Bottom Line

Regular aspirin use may prevent deaths from many causes including cancer, heart attacks, and strokes.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

Footnotes:

  1. American Association for Cancer Research News Release. Regular Aspirin Use in Associated with Lower Cancer Mortality. April 3, 2017. Available online: http://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1036#.Wib80kqnGM9
  2. USPSTF. Final Update Summary: Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. April 2016. Available online: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer
  3. Cao Y, et al. Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer. JAMA Oncol. Published online March 03, 2016. DOI: 10.1001/jamaoncol.2015.6396
  4. U.S. National Library of Medicine. MedlinePlus: Drugs, Supplements, and Herbal Information. Accessed December 2017. https://medlineplus.gov/druginfo/herb_All.html

Prostate Cancer: Diet and Dietary Supplements

Stephanie Portes-Antoine, Brandel France de Bravo, MPH, Caitlin Kennedy, PhD, Anna E. Mazzucco, PhD, and Laura Gottschalk, PhD, Cancer Prevention & Treatment Fund

Prostate cancer is the most common cancer in men in North America. In 2008, approximately 186,000 men in the United States and 25,000 men in Canada were diagnosed with prostate cancer, which accounts for 25% of all cancers in men.[1][2]

Compared to most cancers, prostate cancer usually progresses very slowly, and many men live with it for years and even decades. Once diagnosed, some men decide to undergo treatment to halt the progression of the disease, and others refrain from treatment, preferring instead to closely monitor the cancer’s progression. Those who choose “watchful waiting” do this because the medical and surgical treatments for prostate cancer can cause debilitating side effects, and because most men with prostate cancer will die from something else. This strategy is especially likely for older men in the earliest stage of the disease.

At one time, it was unheard of to suggest that diet might have a role to play in battling prostate cancer. But there is now evidence that certain foods and dietary supplements have an impact on prostate health—both positive and negative. Some foods or supplements appear to promote prostate health and prevent cancer cells from developing, but others should not necessarily be taken by men who already have prostate cancer.

The role of diet drew researchers’ attention when they noticed that prostate cancer rates vary greatly from one country to another, with the highest rates appearing in countries where people tend to eat a lot of fat. Studies also show that men who are obese or have a high fat diet are more likely to have prostate cancer.[2] Diets high in saturated fats, such as the animal fats found in red meat, may pose the greatest risk. The lowest rates of prostate cancer are found in Asian countries where men eat a lot of soy foods, a rich source of naturally occurring phytoestrogens. It was hoped that by increasing men’s intake of phytoestrogens, they might reduce their risk of prostate cancer, slow its progression, or reduce the risk of prostate cancer recurring, but at least three studies have failed to find any protective benefit from phytoestrogens.[4][5][6]

As more and more people take dietary supplements containing antioxidants, studies have been conducted to determine their effect on reducing the risk and growth of cancers, including prostate cancer. Three antioxidants that have received attention with regard to prostate health are vitamin E, selenium, and vitamin D.

Studies comparing men who live in areas of the country with high levels of selenium to men in areas with low levels suggest that this mineral protects against prostate cancer. Selenium is believed to reduce the risk of developing prostate cancer because it keeps cells from proliferating or dying off in a rapid or unusual way. An analysis in 2002 of the Nutritional Prevention of Cancer Trial revealed that the men who took selenium supplements daily were half as likely to be diagnosed with prostate cancer.[7] However, in 2008, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicated that neither selenium nor vitamin E, alone or in combination, was effective for the primary prevention of prostate cancer.[8][9]  In fact, a 2014 report showed that after several more years of observing the men from the SELECT trial, taking vitamin E supplements actually increased the risk of prostate cancer by 17%.[10]  This result led the researchers to discourage men over 55 from taking amounts of vitamin E higher than the recommended dietary allowance (RDA), which is 15 mg of alpha-tocopherol, especially for supplements which contain only the alpha-tocopherol type of vitamin E.

So do antioxidants prevent prostate cancer or not? The case of selenium is an interesting one that helps shed light on this question. Based on the newest research by Philip Kantoff, June Chan, and their colleagues at the Dana-Farber Cancer Institute in Boston, it seems that higher selenium levels in the blood may worsen prostate cancer in many men who already have the disease.[11]

In his earlier research, Dr. Kantoff had found that the risk of developing prostate cancer was modified by a strong interaction between a mitochondrial enzyme (SOD2) and selenium.[12] In his most recent study published in 2009, Dr. Kantoff and his research team measured selenium in the blood of men with prostate cancer and determined which of the two forms of SOD2 the men had: AA or V.9 Among the men with the AA genotype, those with a higher level of selenium in their blood had a lower risk of aggressive prostate cancer. In contrast, the men with the much more common V genotype who had higher levels of selenium in their blood were at an increased risk for aggressive prostate cancer. Unless a man knows which of the two genotypes he has, he may want to avoid taking supplements with selenium, particularly if he has already been diagnosed with prostate cancer.

But what about men who don’t have prostate cancer—should they take selenium?  In 2014, the SELECT trial  found that for men who already had high levels of selenium, taking selenium supplements increased their risk of prostate cancer by 91%.10 Clearly, men should avoid having too much selenium.  As a result of this trial, the researchers have encouraged men over 55 to limit their intake of selenium to the recommended dietary allowance (RDA) of 55 mcgs.

The SELECT findings on selenium don’t mean that antioxidants have no role to play in preventing cancer or slowing its spread. Scientists still have much to learn about antioxidants. Some antioxidants may be helpful and yet some may actually encourage small cancers to grow larger.  A 2013 study by researchers at the Bedford and Addenbrooke’s Hospitals in the U.K. tested the effect of Pomi-T, a supplement that contains broccoli, pomegranate, green tea, and turmeric on the health of men with prostate cancer. After six months, they found that the men taking Pomi-T had a smaller increase or sometimes even a decrease in PSA, a protein that becomes elevated with prostate cancer, as compared to men with prostate cancer who didn’t take Pomi-T. Also, fewer supplement-taking men went on to receive treatment or surgery than non-supplement-taking men. The researchers suggest that the unique blend of polyphenols and antioxidants in the supplement had a beneficial effect on health of these prostate cancer patients.[13]

A study published in 2016 brought yet another antioxidant, vitamin D, into the prostate cancer discussion. Vitamin D is well known for its role in helping build strong bones and teeth, but it may also contribute to the fight against cancer. Higher levels of vitamin D have previously been linked to better breast cancer outcomes (read more here). The prostate cancer study looked at the levels of vitamin D in men who had their prostates removed due to cancer. They found that men who had the most aggressive forms of prostate cancer had lower levels of vitamin D in their blood compared to men with less aggressive forms of cancer.[14] It is not yet known whether higher levels of vitamin D prevent more aggressive forms of prostate cancer or if aggressive prostate cancer lowers levels of vitamin D. Since it is impossible to know if low levels of vitamin D is a cause or effect of aggressive prostate cancer, and since high levels of vitamin D can be dangerous, more research is needed before experts will know if men diagnosed with prostate cancer should try to take more vitamin D.

More studies are needed in order to determine exactly how diet and dietary supplements can be used to prevent prostate cancer and slow its spread. Meanwhile, men should reduce saturated fats as much as possible. While the jury is still out on phytoestrogens, men may benefit from eating more soy products—especially if they are eating them in place of red meat!

For more on cancer and antioxidants, read here.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References

  1. American Cancer Society: Statistics for 2008. Available at http://www.cancer.org. Accessed July 31, 2009.
  2. Canadian Cancer Society: Canadian Cancer Statistics 2008. Available at http://www.cancer.ca
  3. Ma R, Chapman K. A systematic review of the effect of diet in prostate cancer prevention and treatment. Journal of Human Nutrition and Dietetics. Vol (22)2009:187-199.
  4. Ganry O. Phytoestrogens and prostate cancer risk. Preventive Medicine. Vol (41) 2005:1-6.
  5. Ward H, Chapelais G, Kuhnle GC, Luben R, Khaw KT, Bingham S. Lack of Prospective Associations between Plasma and Urinary Phytoestrogens and Risk of Prostate or Colorectal Cancer in the European Prospective into Cancer-Norfolk Study. Cancer Epidemiology Biomarkers & Prevention Vol (17) 2008: 2891-2894.5
  6. Bosland MC, Kato I, Zeleniuch-Jacquotte A, Schmoll J, Rueter EE, Melamed J, Kong MX, Macias V, Kajdacsy-Balla A, Lumey LH, Xie H, Gao W, Walden P, Lepor H, Taneja SS, Randolph C, Schlicht MJ, Meserve-Watanabe H, Deaton RJ, & Davies JA. Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy. JAMA 2013; 310(2): 170-178. doi: 10.1001/jama.2013.7842
  7. Duffield-Lillico AJ, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: A summary report of the Nutritional Prevention of Cancer Trial.Cancer Epidemiology, Biomarkers, and Prevention. Vol (11) 2002: 630-639.
  8. Lippman SM, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). Journal of American Medical Association. Vol (301)2008: 39-51.
  9. Klein EA, et al. SELECT: The next prostate cancer prevention trial-Selenium and Vitamin E Cancer Prevention Trial. Journal of Urology. Vol (166) 2001:1311-1315.
  10. Kristal AR, et al., Baseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer Risk.  Journal of the National Cancer Institute, 2014.
  11. Chan JM et al. Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate-or High-Risk Prostate Cancer. Journal of Clinical Oncology. Vol (27) 2009: 3577-3583.
  12. Li H, et al. Manganese superoxide dismutase polymorphism, pre-diagnostic antioxidant status, and risk of clinical significant prostate cancer. Cancer Research. Vol (65)2005:2498-2505.
  13. Thomas RJ, Williams MMA, Sharma H, Chaudry A, & Bellamy P. A double-blind, placebo RCT evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer: The U.K. National Cancer Research Network (NCRN) Pomi-T study. Results presented at the 2013 Annual Meeting of the American Society of Clinical Oncology. Abstract retrieved on July 12, 2013 from: http://meetinglibrary.asco.org/content/112921-132
  14. Nyame Ya, et al. Associations between serum vitamin D and adverse pathology in men undergoing radical prostatectomy. J Clin Oncol. 2016 Feb 22.

Do high blood pressure and extra weight make prostate cancer deadly?

By Jessica Cote, BS and Anna Mazzucco, PhD
2014

Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths in men in the United States. One in six men will be diagnosed with prostate cancer in his lifetime, with about 90% of cases occurring in men 55 and older, and 71% of deaths occurring in men 75 and older.17

Even though prostate cancer is a leading cause of death, most prostate cancers are not very dangerous. Two key facts are important to remember:

  1. Many older men who aren’t diagnosed with prostate cancer have the disease but will never be harmed by it.
  2. Because prostate cancer usually grows very slowly, most men who are diagnosed with prostate cancer will die of something other than prostate cancer. A recent study showed that only 16% of men in the U.S. diagnosed with prostate cancer died from this disease.18

Although the death rate is relatively low, it is important to find ways to prevent prostate cancer deaths with treatments that do not have serious side effects.

The cause of prostate cancer is unknown, but older men, African-American men, men who drink high amounts of alcohol, farmers, and men who were exposed to Agent Orange pesticides are all at higher risk.19  The high incidence of prostate cancer in Western Europe and North America is thought to be related to a “Western” diet, which is high in refined grains, other processed foods, and saturated fats.20  Meat and dairy products tend to have more saturated fats than other foods, and red meat has more saturated fat than chicken or fish.

Does weight increase the risk?

A 2014 report indicates that being obese can increase a man’s risk of advanced prostate cancer.21  The report was based on meta-analyses that combined and analyzed the results of several large studies. The report analyzed the impact of obesity that was measured three ways, by body mass index (BMI), waist circumference, or waist-hip ratio (WHR), and found a similar link.  This suggests that preventing potentially fatal forms of prostate cancer is another reason to maintain a healthy weight.

What is metabolic syndrome and does it increase the risk of dying from prostate cancer?

Metabolic syndrome refers to a group of factors that increase the risk of coronary artery disease, stroke, and type 2 diabetes.22 The syndrome includes insulin resistance, obesity (especially extra weight around the middle and upper body parts), high blood pressure, and high levels of blood sugar and fats.

Recent research tells us that metabolic syndrome is also related to prostate cancer deaths. A 2012 study of the medical records of more than 289,000 men, published in 2012 in the journal Cancer, found that the risk of getting prostate cancer didn’t seem to be affected by metabolic factors, but the risk of dying from prostate cancer was.23  During a 12-year period, 6,673 men were diagnosed with prostate cancer and 961 died from the disease. Men with a higher BMI, elevated blood pressure, and a high composite metabolic score (from BMI, blood pressure, and blood levels of glucose, cholesterol and triglycerides) were more likely to die from prostate cancer than other men.

The study was well-designed with a large sample size and health information that was collected from patients during many medical exams. However, like most studies, this study wasn’t perfect. Researchers did not record details about the prostate cancer such as tumor stages and patterns of spreading, nor did they consider family history of cancer, medication, socioeconomic status, or other diseases that may have occurred in addition to prostate cancer. All those factors could have influenced the chances of the men dying of prostate cancer. Even so, with hundreds of thousands of men in the study, it is likely that the results should be taken seriously: men can increase their chances of surviving prostate cancer (as well as heart disease) if they reduce metabolic problems.

When we consider this study as well as the 2014 report together, it provides convincing evidence that obesity increases men’s risk of dying of prostate cancer.   While prostate cancer is common among all men, being obese and having the common problems associated with obesity (such as high blood pressure and cholesterol) may make the cancer more aggressive.

What else should men do to lower their risk of getting and dying from prostate cancer?

Cancer screening seems like the best way to reduce the risk of cancer, but that is only true if the screening test is accurate and the treatment is safe and effective.  In 2012, the U.S. Preventive Services Task Force recommended against prostate cancer PSA screening tests for men of any age if they do not present any symptoms of prostate cancer (see: Are Annual Prostate Cancer Screenings Necessary? Should Early Stage Prostate Cancer Be Treated?). The Task Force was convinced that the benefits of PSA-based screening for prostate cancer did not outweigh the harms.24

Even though screening isn’t helpful for men with no symptoms of prostate cancer, it could be very effective at saving the lives of men with symptoms.  If you have one or more symptoms of prostate cancer (trouble urinating, blood in the urine, discomfort in the pelvic area), talk to your doctor about getting a PSA or other test for prostate cancer.

Bottom line: If you’re a man over 50, even if you’ve never been diagnosed with prostate cancer and aren’t presenting any symptoms, the latest research tells us it’s a good idea to do the following:

  1. Eat a diet low in saturated fats. This means limiting intake of high-fat cheeses and other dairy products and choosing leaner cuts of meat.
  2. Watch your intake of sugars and starches– this includes beer, wine and alcohol of all kinds. While 1-2 drinks a day can lower your risk of heart disease and possibly reduce your risk of stroke, more than that can increase your risk of diabetes or related metabolic problems.25
  3. Weigh yourself regularly.  Most men don’t, but if you weigh yourself frequently, it will help you keep your weight down.  If you gain a few pounds, you should eat less and exercise more until your weight is back down.
  4. If you have type 2 diabetes and have been prescribed a special diet or medicine, be sure to stick to it and take your pills as directed.

Pomegranate Juice and Prostate Health

Laura Covarrubias, Cancer Prevention and Treatment Fund

Pomegranate juice contains plenty of antioxidants, but does it improve health, as the ads imply? Pom Wonderful, a large company that makes pomegranate juice and other products from pomegranates, would like you to believe that the juice can prevent or treat a number of health problems, including prostate cancer and erectile dysfunction. However, a close look at the science behind these claims shows that drinking pomegranate juice to treat or prevent prostate cancer and erectile dysfunction might not be worth the cost or the calories.

Prostate cancer is the most common cancer among men, other than skin cancer. (For more on skin cancer, read Tanning Beds: Safe Alternative to Sun? and Running and Skin Cancer Prevention.) Since almost everyone knows someone with prostate cancer, and since treatments can cause erectile dysfunction and incontinence, there is a tremendous desire to find a way to prevent the disease.

Even among men who have not had prostate cancer, erectile dysfunction-the inability to have or maintain an erection (called “ED” in advertisements)-is common. Many men suffering from erectile dysfunction want treatments that are less expensive and more natural than Viagra and other prescription medications.

Drinking pomegranate juice has been touted as an easy solution to decreasing the risk of prostate cancer and improving erectile dysfunction, but does it work? Nearly all of the studies are sponsored by Pom Wonderful, which is selling the products that the studies are evaluating. The company reports having spent at least $35 million on the research; unfortunately, studies sponsored by a product’s manufacturer tend to be biased in favor of the products.[1]

A May 2012 ruling by the Federal Trade Commission (FTC) concluded that Pom Wonderful’s promotional materials about the health benefits of their products are misleading and that their claims that pomegranate juice can treat, prevent, or reduce the risk of certain health conditions (including prostate cancer, erectile dysfunction, and heart disease) were deceptive.[2] Because of federal laws against making misleading disease prevention and treatment claims, the court issued a cease-and-desist order to Pom Wonderful. While the ruling prohibits Pom Wonderful from promoting its juice as a treatment for prostate cancer or erectile dysfunction, it doesn’t prevent the company from making broad claims about pomegranate juice such as that it “promotes prostate health.”

What the Science Says about Prostate Cancer and Pomegranate Juice

Only one study has been published in a peer-reviewed medical journal that looks at the effect of drinking pomegranate juice on prostate cancer. This 2006 study, funded by Pom Wonderful, is often used by the company to back its claims that their juice can help fight prostate cancer.[3] Only 46 men treated with either surgery or radiation for prostate cancer participated. All the men had rising prostate-specific antigen (PSA) levels, which is interpreted as a sign that their prostate cancer had come back, and all were given 8 ounces of Pom Wonderful to drink daily for a period of two years. The study found that the men’s rising PSA levels slowed, which can mean that their cancers were no longer growing as fast. To read more about PSA tests, click here.

In most scientific research, some patients receive a new treatment and the others receive either a placebo (sugar pill) or an older treatment. The Pom study was poorly designed because all the men drank the juice, making it impossible to evaluate the impact of the juice. Since PSA levels vary over time, we can’t know if PSA levels dropped because of the juice or would have dropped even without the juice.  In addition, the study only evaluated 46 men, all of whom had been treated for prostate cancer.  This small number of prostate cancer patients is not large enough to draw conclusions about all men, or even all men who have been treated for prostate cancer.

This 2006 study also looked at samples of cancer cells that were taken from other men with prostate cancer-not the same men who drank the pomegranate juice. These cancer cells were then treated with serum – a component of blood – from the men who drank pomegranate juice to see if the cancer cells stopped growing. The study found that cancer cells died when treated with the serum.  That sounds impressive, but there are many reasons why the serum could have caused the cancer cells to die. The researchers called for a future study with a control group (where cancer cells are treated with nothing), but six years later no study like that has been published.

Studies of pomegranate juice on mice and on human cells were more promising, but also not conclusive. One study funded by the U.S. Public Health Service, a government agency, looked at the effect of pomegranate extract – a very concentrated form of pomegranate juice – on prostate cancer cells that were taken from patients but grown outside of the body.[4] They found that the growth of cancer cells treated with the pomegranate extract was slower in comparison to the cancer cells not treated with the extract. In this same study, scientists also looked at the effects of pomegranate extract on the tumor size of mice with prostate cancer. They saw that the growth rate of the tumors in mice treated with the extract was slower in comparison to the growth rate of tumors in the mice that were not treated.

Another laboratory study found that more prostate cancer cells died in the samples treated with pomegranate juice concentrate provided by Pom Wonderful than in samples treated with different types of pomegranate extract.[5] The researchers believe that the many different chemical compounds in pomegranate juice work together to kill cancer cells, and that the pomegranate extract did not have all of these compounds and so did not have as strong of an effect. However, this study does not tell us if drinking pomegranate juice-rather than applying it to cancer cells-can prevent or treat cancer.  Even if there were research indicating a benefit from drinking the juice, how much juice would men have to drink?

Pom has also funded studies on clogged arteries and diabetes, which required people to drink 8 ounces of pomegranate juice every day (these studies were also inconclusive about the effects of pomegranate juice).[6,7] Even if 8 ounces a day was effective at lowering prostate cancer risk or improving health, this is a solution that not everyone could afford.  The cost of the juice, which would not be covered by health insurance, would be about $780 a month.[8] Drinking 8 ounces of Pom Wonderful adds an additional 160 calories per day, which equals 1,120 calories a week and 4,800 calories a month.  Unless the juice replaces an equally caloric drink, this could increase a person’s weight, which in turn increases the risk of prostate cancer and several other types of cancer (Weight and Cancer: The Latest Research).

What other alternatives are there?  Diets high in fiber and low in meat products and saturated fats have been linked to a lower risk of prostate cancer in men, and these diets also have other positive health effects such as reducing the risk of developing diabetes, heart disease, and stroke.[9,10,11] To learn more about the connections between diet and prostate cancer, read here.

What the Science Says about Erectile Dysfunction and Pomegranate Juice

There is even less evidence behind Pom Wonderful’s claims that drinking pomegranate juice decreases erectile dysfunction than there is about prostate cancer or other illnesses. Two studies used by Pom Wonderful to back these claims were conducted on rabbits – not humans.[12,13]These studies found that antioxidants (not pomegranate juice specifically) may be useful against erectile dysfunction, although no definite conclusions were made even for rabbits, and certainly not for humans.

The only study of humans used by Pom Wonderful divided the 53 participants with erectile dysfunction into two groups.[14] One group was assigned to drink pomegranate juice every day for the first 28 days, while the other group drank a placebo drink. After 28 days, the men answered questions about their erectile function. For the next two weeks, both groups stopped drinking their assigned drink (juice or placebo) – this time is known as a “washout” period. Research studies use washout periods to make sure that any effects of the treatment do not continue to be measured when the person begins drinking the new drink. After the washout period, the groups switched drinks so that the group that drank pomegranate juice drank the placebo for 28 days (and vice versa). Again, the men answered the same questions about their erectile function. Overall, the researchers did not find any statistically significant difference between the two groups.  Although there was a slight decrease in erectile dysfunction among the men drinking the pomegranate juice, the difference was small and could have occurred by chance. The researchers called for a larger and longer study to determine if pomegranate juice really does improve erectile dysfunction. We agree.

More Research Needed

Better research on men is needed to determine if regularly drinking pomegranate juice or taking pomegranate extract pills prevents or helps treat prostate cancer, erectile dysfunction, or other conditions. In the meantime, there is no harm in drinking pomegranate juice as long as it does not contribute to overweight or obesity.  Men who choose to drink pomegranate juice should consider the extra calories and cost.

Bottom Line:

  • There is no strong evidence to support the claim that pomegranate juice protects against prostate cancer or helps with erectile dysfunction.
  • Age increases the likelihood of prostate cancer and erectile dysfunction, and weight gain can also increase the chances of getting prostate cancer or having it return after treatment.[15]
  • If you or a loved one is undergoing treatment for prostate cancer, pomegranate juice is not an effective alternative.

References:

  1. Lexchin J, Bero L, Djulbegovic B. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. Bmj. 2003;326(May). Available at: http://www.bmj.com/content/326/7400/1167.short. Accessed June 6, 2012.
  2. United States of America Federal Trade Commission. Initial Decision. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1245105.
  3. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006;12(13):4018-26. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16818701. Accessed March 28, 2012.
  4. Malik A, Afaq F, Sarfaraz S, et al. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(41):14813-8. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1253570&tool=pmcentrez&rendertype=abstract.
  5. Seeram NP, Adams LS, Henning SM, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. The Journal of nutritional biochemistry. 2005;16(6):360-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15936648. Accessed May 24, 2012.
  6. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clinical nutrition (Edinburgh, Scotland). 2004;23(3):423-33. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15158307. Accessed May 2, 2012.
  7. Rosenblat M, Hayek T, Aviram M. Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages. Atherosclerosis. 2006;187(2):363-71. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16226266. Accessed May 13, 2012.
  8. United States of America Federal Trade Commission. Initial Decision. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1245105.
  9. Cohen JH, Kristal a R, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. Journal of the National Cancer Institute. 2000;92(1):61-8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10620635.
  10. Ma RW-L, Chapman K. A systematic review of the effect of diet in prostate cancer prevention and treatment. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2009;22(3):187-99; quiz 200-2. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19344379. Accessed June 10, 2012.
  11. Anderson JW, Baird P, Davis RH, et al. Health benefits of dietary fiber. Nutrition reviews. 2009;67(4):188-205. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19335713. Accessed March 3, 2012.
  12. Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. The Journal of urology. 2005;174(1):386-93. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15947695. Accessed July 16, 2012.
  13. Zhang Q, Radisavljevic ZM, Siroky MB, Azadzoi KM. Dietary antioxidants improve arteriogenic erectile dysfunction. International journal of andrology. 2011;34(3):225-35. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20584092. Accessed July 16, 2012.
  14. Forest CP, Padma-Nathan H, Liker HR. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study. International journal of impotence research. 2007;19(6):564-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17568759. Accessed July 16, 2012.
  15. Kaluza J, Wolk A, Larsson SC. Red Meat Consumption and Risk of Stroke: A Meta-Analysis of Prospective Studies. Stroke; a journal of cerebral circulation. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22851546. Accessed August 9, 2012.

Physician Groups Make Recommendations to Reduce Healthcare Costs

Nyedra W. Booker, PharmD, MPH, Cancer Prevention and Treatment Fund

  • Does an 18-year-old girl need a pap smear?
  • Should a patient with a mild sinus infection be given antibiotics?

You might be surprised that the answer to both questions is NO according to leading physicians.

In an effort to improve medical care in the U.S. and save healthcare dollars at the same time, each of nine U.S. medical groups recently proposed a list of Five Things Physicians and Patients Should Question. This is a bold move by medical groups who collectively represent almost 375,000 physicians.  Currently, doctors are paid more for ordering more tests and diagnostic procedures, so these recommendations  are not financially beneficial to the physicians involved, but have the potential for reducing the cost of medical care for patients, health insurance companies, and government health programs such as Medicare, Medicaid, and Veterans healthcare.

The medical groups represent a wide range of medical care.  The nine groups include the American Academy of Allergy, Asthma & Immunology; American Academy of Family Physicians; American College of Cardiology; American College of Physicians; American College of Radiology; American Gastroenterological Association; American Society of Clinical Oncology; American Society of Nephrology and the American Society of Nuclear Cardiology.

Recommendations

Here are just a few of the groups’ recommendations:

Hives – Routine diagnostic testing (such as immunoglobulin E (IgE), a skin prick or blood test for allergies) is not recommended for patients with chronic hives, because such testing is usually ineffective at identifying the cause. [American Academy of Allergy, Asthma & Immunology]

Pap Smears – Routine pap smears to screen for cervical cancer are not recommended for women under the age of 21. [American Academy of Family Physicians]

Cardiac Stress Test – Cardiac stress test imaging (a procedure where dye is inserted into the blood stream and images show how well the blood is flowing through the heart) is not recommended for cardiac patients at their annual check-ups unless symptoms are present. [American College of Cardiology]

X-Rays and MRIs for Back Pain – Imaging (X-rays, MRIs) is not recommended for a patient with lower back pain unless a specific cause has been identified. [American College of Physicians]

MRIs and CCTs of the Brain – Imaging of the brain, including MRIs and CCTs (cranial computed tomography), is not recommended for a patient with a headache unless specific risk factors have been identified. [American College of Radiology]

Colorectal Cancer Screening– Colorectal cancer screening by any method (including flexible sigmoidoscopy, computed tomography colonography, double-contrast barium enema test) should be repeated every 10 years in low to average-risk patients who received a normal result at their last colonoscopy screening.  This is less frequently than previous recommendations.  It is recommended that people get their first colonoscopy at age 50. [American Gastroenterological Association]

Breast Cancer Testing – Imaging (PET, CT and radionuclide bone scans) is not recommended for patients with early-stage breast cancer at low risk for metastasis (cancer spreading to other parts of the body). [American Society of Clinical Oncology]

Cancer Screening – Routine cancer screenings (including colonoscopy, mammography and pap smears) are not recommended for patients on dialysis who have a short life expectancy, unless specific signs and symptoms are present. [American Society of Nephrology]

Chest Pains – Routine cardiac imaging including a stress echocardiogram (which  uses ultrasound to show how well the heart is pumping blood) is not recommended for a patient with chest pains who is at low risk for a heart attack or cardiac-related death, is able to exercise, and has a normal electrocardiogram (EKG).[American Society of Nuclear Cardiology][1]

A complete list of all 45 recommendations is available at: http://choosingwisely.org

How Will This Help?

Healthcare spending in the United States reached almost $2.6 trillion in 2010 and is expected to rise to around $4.6 trillion by 2020 unless major changes are made to eliminate unnecessary procedures, according to the Centers for Medicare & Medicaid Services.[2] An increase in the number of people living with chronic illnesses, rising prescription drug prices, and the high administrative costs of managing healthcare programs will contribute to increasing costs. While many continue to debate the exact reasons why healthcare spending is out of control, most agree that something needs to be done immediately.

In 2011, the American Board of Internal Medicine Foundation (ABIM) announced the Choosing Wisely campaign, and the National Physicians Alliance helped develop a multi-year initiative that would promote discussion among physicians, patients and consumer groups, aimed at decreasing healthcare costs by reducing unnecessary tests and procedures. Each participating group of physicians was asked to develop a list of five recommendations based on evidence from research findings. These recommendations were specific to their respective medical fields.

While many doctors and health experts understand that more medical care, and more expensive medical care, is not necessarily better medical care, studies show that the American public is wary of health care guidelines, even when they’re based on strong evidence. Patients and consumers tend to assume that running more tests and relying on newer, more costly technologies translate into health improvements (see Is Newer and More Expensive Care Better?).  As for doctors, the need to pay for expensive new imaging devices by charging for their use, the desire to give patients a clear diagnosis, and concerns about harming a patient by missing a diagnosis can all contribute to ordering unnecessary imaging and other tests.

Given this divide, it’s not surprising that Choosing Wisely has generated praise and concern. While many are praising the initiative as a step in the right direction to reduce the staggering cost of healthcare in the U.S., others question whether these cost-cutting strategies will come at the expense of good patient care.

Next Steps

The American Board of Internal Medicine Foundation and the National Physicians Alliance will continue to work with the nine medical specialty groups and several partnering organizations, including Consumer Reports and the American Association of Retired Persons (AARP), to develop tools and resources to help physicians discuss healthcare decisions with their patients. There will also be at least eight additional medical specialty groups joining the initiative and releasing their recommendations in the fall of 2012.

References:

  1. Choosing Wisely: An Initiative of the ABIM Foundation. Accessed April 04, 2012. http://choosingwisely.org/?page_id=13.
  2. Centers for Medicare & Medicaid Services. “National Health Expenditure Projections 2010-2020.” Accessed April 09, 2012. https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/Downloads/proj2010.pdf

 

Having Trouble Sleeping? Pills are not a Safe Solution

Brandel France de Bravo, MPH, Cancer Prevention and Treatment Fund

When we hear “sleeping pills,” most of us think of prescription drugs such as Ambien (generic name zolpidem), Restoril (temazepam), and Lunesta (eszopiclone).  While prescription sleep medications are big business — consumers spent $2 billion on them in 2010[1] — many people with trouble sleeping turn to over-the-counter antihistamines such as Tylenol PM and Benadryl, which are also considered hypnotic drugs.[2] But the use of these hypnotic drugs may take a nosedive in light of the findings of a study published in February 2012 in the prestigious British Medical Journal. Led by researchers at the Scripps Clinic Viterbi Family Sleep Center in California, the study shows that people who take hypnotic drugs are significantly more likely to be diagnosed with cancer or to die within the next two and a half years than people who don’t take them. Author Dr. Daniel Kripke estimates that these popular sleep medications could have caused 320,000 to 507,000 deaths in 2010.

The researchers looked at 10,529 primary care patients who were prescribed hypnotic drugs between 2002 and 2007 and compared the health of each of them to at least two very similar patients without such prescriptions who were the same sex, ethnicity, marital status, smoking status, and had similar health conditions, alcohol use and body mass index (a combination of height and weight). All patients, who were followed for 2.5 years on average, were from a Pennsylvania clinic that serves a mainly low-income population.

Patients who were prescribed sleeping pills were at least three to five times more likely to have died during the study than were the patients not prescribed sleeping pills. Even the patients who were prescribed fewer than 18 pills per year were at higher risk of dying: 3.6 times higher. Patients who were prescribed more than 132 pills a year were more than five times as likely to die.

The researchers were careful to exclude from the study patients who were diagnosed with cancer before the study or very early in the study. In spite of this precaution, they found that patients who were prescribed more than 18 pills a year had an increased cancer risk, with the heavy users (over 132 pills prescribed per year) having a 35% greater risk than those with fewer pills prescribed.  Among those with prescriptions for sleeping pills, the increased risk of their developing lymphoma, lung cancer, colon and prostate cancer was greater than the risk from being a current smoker.

Before this study, there were at least 18 other studies showing an increased risk of death for people taking sleeping pills, and several also showed an increased risk of cancer.  However, this study is especially well-designed and the only one that includes the newer, short-acting class of popular sleeping pills known as nonbenzodiazepines . These were generally believed to be safer than previous generations of sleeping pills because they wear off more quickly. In fact, until this study, the scariest side effect was seemingly inexplicable weight gain due to night time raids on the refrigerator while sleep walking.

Among study participants, the most commonly prescribed sleeping pill was zolpidem (a nonbenzodiazepine marketed as Ambien, Edluar, or Zolpimist), followed by temazepam (a benzodiazepine).  However, prescriptions for the use of any hypnotic drug as a sleep aid was associated with a significant increase in the risk of death, including eszopiclone (”Lunesta”), zaleplon (”Sonata”), and barbiturates, as well as prescriptions for diphenhydramine, an antihistamine used in many over-the-counter sleep aids. The average age of patients was 54, but the study found harm associated with sleeping pill use in every age group.

All the sleeping pills showed a similar increased risk of death except Lunesta , which showed a more than 500% increased risk compared to any of the other sleeping pills.  However, Lunesta was a relatively new drug at the time of the study, and relatively few people took it.  For that reason, it is not possible to say whether the risk of Lunesta is really higher.

One shortcoming of the study is that getting a prescription for a sleeping pill is not the same as taking sleeping pills.  It is possible that some of the people with prescriptions, especially for small numbers of pills, never took any of them.  It is also possible that people who did not have prescriptions for sleeping pills took over-the-counter antihistamines to help them fall asleep, instead of the prescription version of the same pills.  However, those shortcomings would tend to underestimate the risk of sleeping pills, rather than over-estimate the risks.

What could possibly explain these increased risks?  Are people who are prescribed sleeping pills more anxious or stressed out? There is evidence that they are more likely to have car accidents or to fall down, probably because of the residual effects of the drugs during the day.  Other studies show an increase in infections among people taking sleeping pills, and that can also increase the risk of cancer and death from other causes.   These other studies all suggest that sleeping pills really do increase the risk of dying and there are no logical explanations to explain away the substantial increased risks found in this study, especially the increased risk of cancer.

While the researchers can’t say for sure that the sleeping pills caused death or cancer, many people who used to take these medications should think about these new research findings and consider other, safer ways to fall asleep.  The sleep specialists who conducted the research suggest that since hypnotics have limited benefits, old-fashioned sleep aids like warm milk, as well as cognitive-behavioral approaches that can be taught and used for the rest of your life, would be excellent alternatives.  If you decide to toss your sleeping pills, be sure to see our article Drugs in the Drinking Water for tips on safe medicine disposal.

References:

  1. IMS data cited in The Wall Street Journal. Dawn of A New Sleep Drug. July 19, 2011.
  2. Kripke DF, Langer RD, Kline LE. Hypnotics’ association with mortality or cancer: a matched cohort studyBritish Medical JournalOpen 2012;2:e000850 doi:10.1136/bmjopen-2012-000850