Task Force Recommends Against Hormones for Post-Menopausal Women

By Jennifer Corbett Dooren

A federal task force has once again examined the use of hormone replacement therapy, and is again recommending against hormones for preventing fractures, dementia and other chronic diseases in women who are already past menopause.

The U.S. Preventive Services Task Force issued the draft guidelines on the use of estrogen and progestin to take into account new findings from the landmark Women’s Health Initiative study that looked at hormone use, along with other studies issued in the past decade.

The recommendations don’t apply to women who are experiencing menopause and use hormones to treat hot flashes and other symptoms.

The federally funded Women’s Health Initiative, known as WHI, was halted in 2002 when initial results showed women taking a combination of estrogen and progestin had a higher risk of breast cancer, heart disease and stroke than women who received a placebo. Although participants stopped taking hormones at that time, researchers have continued to monitor them to analyze outcomes.

In 2002, the task force issued recommendations against combination use of estrogen and progestin in post-menopausal women, and later advised against estrogen-only use in these women as well.

Dr. Kirsten Bibbins-Domingo, a task force member and an associate professor of medicine, epidemiology and biostatistics at the University of California, San Francisco, said the recommendations for post-menopausal women haven’t changed. But, she said, it was important to take a new look at the issue given the additional information that has come out in recent years. For example, one study suggested women taking estrogen-only therapy had a lower risk of invasive breast cancer.

The task force notes that the vast majority of women currently using hormone therapy are younger and transitioning through menopause. The FDA has approved hormones to prevent menopausal symptoms and to prevent fractures, according to the task force. The products carry a boxed-warning stating that estrogen with or without progestin “should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risk for the individual woman.”

As the Health Blog noted recently, much research suggests that the benefits of hormone-replacement therapy outweigh the risks for women who start it near menopause. Data from WHI suggests much of the harm seen in women was among those in their 60s and 70.

Unlike previous task force recommendations, such as one issued earlier this month advising against prostate-cancer screening with a PSA test in men, the updated recommendation on hormone-replacement therapy for postmenopausal women aren’t controversial. However, the task force is taking comments on the draft hormone therapy recommendations from now until June 26.

http://palmbeachresearch.com/?p=1535

Sugar can make you dumb, US scientists warn

Eating too much sugar can eat away at your brain power, according to US scientists who published a study showing how a steady diet of high-fructose corn syrup sapped lab rats' memories.
Researchers at the University of California Los Angeles (UCLA) fed two groups of rats a solution containing high-fructose corn syrup - a common ingredient in processed foods - as drinking water for six weeks.
One group of rats was supplemented with brain-boosting omega-3 fatty acids in the form of flaxseed oil and docosahexaenoic acid (DHA), while the other group was not.

Before the sugar drinks began, the rats were enrolled in a five-day training session in a complicated maze. After six weeks on the sweet solution, the rats were then placed back in the maze to see how they fared.
"The DHA-deprived animals were slower, and their brains showed a decline in synaptic activity," said Fernando Gomez-Pinilla, a professor of neurosurgery at the David Geffen School of Medicine at UCLA.
"Their brain cells had trouble signaling each other, disrupting the rats' ability to think clearly and recall the route they'd learned six weeks earlier."
A closer look at the rat brains revealed that those who were not fed DHA supplements had also developed signs of resistance to insulin, a hormone that controls blood sugar and regulates brain function.
"Because insulin can penetrate the blood-brain barrier, the hormone may signal neurons to trigger reactions that disrupt learning and cause memory loss," Gomez-Pinilla said.
In other words, eating too much fructose could interfere with insulin's ability to regulate how cells use and store sugar, which is necessary for processing thoughts and emotions.
"Insulin is important in the body for controlling blood sugar, but it may play a different role in the brain, where insulin appears to disturb memory and learning," Gomez-Pinilla said.
"Our study shows that a high-fructose diet harms the brain as well as the body. This is something new."
In the US, high-fructose corn syrup is commonly found in soft drink, condiments, applesauce, baby food and other processed snacks.
The average American consumes more than 40 pounds (18 kilograms) of high-fructose corn syrup per year, according to the US Department of Agriculture.
While the study did not say what the equivalent might be for a human to consume as much high-fructose corn syrup as the rats did, researchers said it provides some evidence that metabolic syndrome can affect the mind as well as the body.
"Our findings illustrate that what you eat affects how you think," said Gomez-Pinilla.
"Eating a high-fructose diet over the long term alters your brain's ability to learn and remember information. But adding omega-3 fatty acids to your meals can help minimise the damage."
The study appeared in the Journal of Physiology

A Stem-Cell-Based Drug Gets Approval in Canada

In a boost for the field of regenerative medicine, a small biotechnology company has received regulatory approval in Canada for what it says is the first manufactured drug based on stem cells.

The company, Osiris Therapeutics of Columbia, Md., said Thursday that Canadian regulators had approved its drug Prochymal, to treat children suffering from graft-versus-host disease, a potentially deadly complication of bone marrow transplantation.

“It’s really a good day for the concept and the hope behind stem cell therapies becoming a reality,” C. Randal Mills, the chief executive of Osiris, said in an interview.

Prochymal is a preparation of mesenchymal stem cells, which are obtained from the bone marrow of healthy young adult donors. The stem cells are separated out from the marrow and expanded in culture, so that one donation is enough to make as many as 10,000 doses.

Because these are adult stem cells, they do not raise the ethical concerns of embryonic stem cells, whose creation usually involves the destruction of human embryos.

Graft-versus-host disease occurs when the immune cells in a bone-marrow transplant see the recipient’s organs as foreign and attack them, causing potentially severe damage to the skin, liver and digestive tract. This happens most often when the donor is not an exact match for the recipient.

Doctors try using steroids or other drugs to damp the immune attack, but in many cases those don’t work, and the patient may die.

Prochymal is approved in Canada for children whose condition is not controlled by steroids. In a small trial, about 60 percent of such children had a clinically meaningful response to the drug, Osiris said.

“Any drug or a cell that has activity in the patients with severe disease is exciting and important,” said Dr. Joanne Kurtzberg, director of the pediatric blood and marrow transplant program at Duke University Medical Center.

Dr. Kurtzberg, who helped Osiris present its case to Canadian regulators, said the drug has saved some children’s lives from graft-versus-host disease and could lead to more successful bone marrow transplants.

Osiris is not expected to gain much revenue from patients with a rare disease in Canada. But it is a welcome success for a 20-year-old company that has had its share of failures.

In 2009, Prochymal failed in two late-stage clinical trials, showing little to no advantage over placebo in treating graft-versus-host disease. The company is also trying to develop Prochymal as a treatment for Crohn’s disease, diabetes, heart attacks and other illnesses, but has had some failures there as well.

Sanofi, the big French company that had the rights to sell Prochymal outside North America, said in February that it had discontinued its work on the drug.

Dr. Mills, Osiris’s chief executive, said the company realized the drug was most effective in the most severe cases of graft-versus-host-disease that did not respond to steroids, leading it to do the small trial in children.

Dr. Mills said that the Food and Drug Administration indicated that it would require more data before approval, prompting Osiris to seek approval in Canada first. He said the company would apply to the F.D.A. later this year.

Stem cells are already used in medicine. Bone marrow or stem cell transplants are used to treat various cancers and genetic diseases. But those transplants are medical procedures, not products sold by a drug company.

There are cell therapies that have been approved by regulators, such as Carticel, a Genzyme product that uses a patient’s own cells to repair cartilage in injuries. Last year the F.D.A. approved a cord blood product for use in transplantation. Those products are not manufactured for off-the-shelf use like Prochymal is, Dr. Mills said.

Osiris announced the approval after regular stock trading ended. After hours, the stock rose 14 percent to $6.00.

Study finds java drinkers live longer

One of life's simple pleasures just got a little sweeter. After years of waffling research on coffee and health, even some fear that java might raise the risk of heart disease, a big study finds the opposite: Coffee drinkers are a little more likely to live longer. Regular or decaf doesn't matter.
The study of 400,000 people is the largest ever done on the issue, and the results should reassure any coffee lovers who think it's a guilty pleasure that may do harm.
"Our study suggests that's really not the case," said lead researcher Neal Freedman of the National Cancer Institute. "There may actually be a modest benefit of coffee drinking."
No one knows why. Coffee contains a thousand things that can affect health, from helpful antioxidants to tiny amounts of substances linked to cancer. The most widely studied ingredient — caffeine — didn't play a role in the new study's results.
It's not that earlier studies were wrong. There is evidence that coffee can raise LDL, or bad cholesterol, and blood pressure at least short-term, and those in turn can raise the risk of heart disease.
Even in the new study, it first seemed that coffee drinkers were more likely to die at any given time. But they also tended to smoke, drink more alcohol, eat more red meat and exercise less than non-coffee-drinkers. Once researchers took those things into account, a clear pattern emerged: Each cup of coffee per day nudged up the chances of living longer.
The study was done by the National Institutes of Health and AARP. The results are published in Thursday's New England Journal of Medicine.
Careful, though — this doesn't prove that coffee makes people live longer, only that the two seem related. Like most studies on diet and health, this one was based strictly on observing people's habits and resulting health. So it can't prove cause and effect.
But with so many people, more than a decade of follow-up and enough deaths to compare, "this is probably the best evidence we have" and are likely to get, said Dr. Frank Hu of the Harvard School of Public Health. He had no role in this study but helped lead a previous one that also found coffee beneficial.
The new one began in 1995 and involved AARP members ages 50 to 71 in California, Florida, Louisiana, New Jersey, North Carolina, Pennsylvania and Atlanta and Detroit. People who already had heart disease, a stroke or cancer weren't included. Neither were folks at diet extremes — too many or too few calories per day.
The rest gave information on coffee drinking once, at the start of the study. "People are fairly consistent in their coffee drinking over their lifetime," so the single measure shouldn't be a big limitation, Freedman said.
Of the 402,260 participants, about 42,000 drank no coffee. About 15,000 drank six cups or more a day. Most people had two or three.
By 2008, about 52,000 of them had died. Compared to those who drank no coffee, men who had two or three cups a day were 10 percent less likely to die at any age. For women, it was 13 percent.
Even a single cup a day seemed to lower risk a little: 6 percent in men and 5 percent in women. The strongest effect was in women who had four or five cups a day — a 16 percent lower risk of death.
None of these are big numbers, though, and Freedman can't say how much extra life coffee might buy.
"I really can't calculate that," especially because smoking is a key factor that affects longevity at every age, he said.
Coffee drinkers were less likely to die from heart or respiratory disease, stroke, diabetes, injuries, accidents or infections. No effect was seen on cancer death risk, though.
Other research ties coffee drinking to lower levels of markers for inflammation and insulin resistance. Researchers also considered that people in poor health might refrain from drinking coffee and whether their abstention could bias the results. But the study excluded people with cancer and heart disease — the most common health problems — to minimize this chance. Also, the strongest benefits of coffee drinking were seen in people who were healthiest when the study began.
About two-thirds of study participants drank regular coffee, and the rest, decaf. The type of coffee made no difference in the results.
Hu had this advice for coffee lovers:
— Watch the sugar and cream. Extra calories and fat could negate any benefits from coffee.
— Drink filtered coffee rather than boiled — filtering removes compounds that raise LDL, the bad cholesterol.
Researchers did not look at tea, soda or other beverages but plan to in future analyses.
Lou and Mariann Maris have already compared them. Sipping a local brew at a lakefront coffee shop, the suburban Milwaukee couple told of how they missed coffee after briefly giving it up in the 1970s as part of a health kick that included transcendental meditation and eating vegetarian.
Mariann Maris switched to tea after being treated for breast cancer in 2008, but again missed the taste of coffee. It's one of life's great pleasures, especially because her husband makes it, she said.
"Nothing is as satisfying to me as a cup of coffee in the morning," she said.
___
Online:
New England Journal: http://www.nejm.org

Dietary Supplements Increase Cancer Risk

Beta-carotene, selenium and folic acid – taken up to three times their recommended daily allowance, these supplements are probably harmless. But taken at much higher levels as some supplement manufacturers suggest, these three supplements have now been proven to increase the risk of developing a host of cancers.
"It's not that these nutrients are toxic – they're essential and we need them, but we need them in a certain balance," says Tim Byers, MD, MPH, professor of epidemiology at the Colorado School of Public Health and associate director for prevention and control at the University of Colorado Cancer Center.
Byers is senior author of a commentary recently published in the Journal of the National Cancer Institute that discusses the clinical and policy implications of the increased cancer risk from high dose dietary supplements.
"We have a window into less than half of the biology of what these nutrients are doing," Byers says. "We say generalized things about them, calling them an antioxidant or an essential mineral, but true biology turns out to be more complex than that. The effects of these supplements are certainly not limited to the label we give them. And, as we've seen, sometimes the unintended effects include increased cancer risk."
Currently the FDA regulates dietary supplements as food, but, as Byers and colleagues suggest, supplements, especially at high doses, are more accurately described as inhabiting a mid-ground between food and drugs. Like drugs, supplement ingredients are biologically active – sometimes for better and sometimes for worse
"We need to do a better job as a society in ensuring that the messages people get about value versus risk is accurate for nutritional supplements," Byers says. "My conclusion is that taking high doses of any particular nutrient is more likely to be a bad thing than a good thing."
Source: University of Colorado, Denver

Drinking coffee = protection against strokes

May 11, 2012 (London, United Kingdom) — A new meta-analysis, including the most contemporary studies that have examined coffee consumption and risk of cardiovascular events in a general population, has found that moderate intake may help protect against ischemic stroke [1].

Presenting the results at the recent European Society of Hypertension (ESH) European Meeting on Hypertension 2012, Dr Lanfranco D'Elia (Federico II University of Naples, Italy) told heartwire : "The first message is that coffee intake is not associated with a higher risk of stroke," which he says is reassuring. "Second, the analysis showed that low to moderate intake--one to three cups of coffee per day--was associated with lower risk of stroke in the general population, across a wide range of countries, including some in Europe, the US, and Japan."

However D'Elia stressed that these results apply to the general population only and that findings with regard to coffee intake and risk in those with cardiovascular disease have been conflicting. Nevertheless, he believes that "one coffee a day is not dangerous for people with heart disease."

Protective effect independent of most identifiable confounders

D'Elia and colleagues performed a meta-analysis of the available prospective studies, including those that estimated baseline coffee consumption and risk of stroke in the general population, from 1966 to 2011. However, the majority of studies included were performed in the late 2000s, including a recent Swedish study and one from the Netherlands.

One to three cups of coffee per day was associated with lower risk of stroke in the general population.
For this analysis, coffee consumption was stratified into moderate (one to three cups/day), high (three to six), and very high (six or more) and compared with the reference category (zero to one). For each study, the values of relative risk (RR) and their confidence interval were extracted and then combined using a random effect model. Eight general-population studies were included in the analysis, for a total of 11 cohorts (484 757 participants, 7272 stroke events, follow-up two to 24 years).

In the pooled analysis, habitual moderate coffee consumption was associated with decreased risk of stroke (RR 0.86, 95% CI 0.75–0.98; p < 0.02).

Stroke risk in the high-consumption category showed a trend in the same direction, toward a reduction (RR 0.87, 95% CI 0.70–1.08; p=0.02), which reached statistical significance upon sensitivity analysis with the exclusion of a single outlier study (RR 0.81, 95% CI 0.70–0.95; p=0.01).

Habitual very high coffee consumption was not associated with any effect on stroke risk (RR 1.05, p=0.71).

D'Elia said that unlike low to moderate coffee intake, both "high" and "very high" consumption showed a significant heterogeneity between studies.

Statistical analysis did not find any significant sources of heterogeneity (length of follow-up, publication year, gender, countries, etc) that affected the relationship between coffee intake and stroke risk, but he noted, "We cannot exclude the potential limitations of the analysis around the standardization of coffee preparation or different types of coffee.

"The results of this meta-analysis, which included prospective studies of samples of the general population, indicate that coffee consumption is not associated with a higher risk of stroke and that actually habitual moderate consumption may exert a protective effect independently from most identifiable confounders," he concluded.

Diabetes Drug Could Also Treat Leading Cause of Blindness

Article on Website 

University of Texas Medical Branch at Galveston researchers have discovered that a drug already prescribed to millions of people with diabetes could also have another important use: treating one of the world’s leading causes of blindness.

In laboratory rat and cell-culture experiments, the scientists found that metformin, which is commonly used to control blood sugar levels in type 2 diabetes, also substantially reduced the effects of uveitis, an inflammation of the tissues just below the outer surface of the eyeball. Uveitis causes 10 to 15 percent of all cases of blindness in the United States, and is responsible for an even higher proportion of blindness globally. The only treatment now available for the disorder is steroid therapy, which has serious side effects and cannot be used long-term.

“Uveitis has various causes — the most common are infectious diseases and autoimmune disorders— but they all produce inflammation within the eye,” said UTMB professor Kota V. Ramana, senior author of a paper on the study now online in the journal Investigative Ophthalmology & Visual Science. “Metformin inhibits the process that causes that inflammation.”

The scientists discovered metformin’s efficacy when they tested it in rats given an endotoxin that mimicked the inflammatory effects of bacterial infection. The results showed clearly that metformin was a very effective anti-uveitis agent.

“We found that the drug is therapeutic as well as preventive — if we gave our rats the drug beforehand, they didn’t develop uveitis, and if we gave it after uveitis had developed, it was therapeutic,” said UTMB professor Satish Srivastava, also an author of the IOVS paper. “Metformin’s strong anti-inflammatory properties make this possible.”

According to the researchers, metformin works by activating an enzyme called AMPK, which in turn damps down the activity of the protein NF-kappa B. The inhibition of NF-kappa B suppresses the production of inflammatory signaling molecules — cytokines and chemokines — needed to initiate and sustain uveitis.

Because metformin is already used so widely as a therapy for diabetes, the UTMB scientists believe that it has a good chance of being rapidly adopted as an anti-uveitis drug.

“I think after a few more pre-clinical studies are done, we can get this drug to patients in a shorter time than usual,” Ramana said. “Its safety is already known, so all that we need to see is its efficacy in humans.”

Source: University of Texas Medical Branch at Galveston

Breast cancer is rare in men, but they fare worse

Men rarely get breast cancer, but those who do often don’t survive as long as women, largely because they don’t even realize they can get it and are slow to recognize the warning signs, researchers say.

On average, women with breast cancer lived two years longer than men in the biggest study yet of the disease in males.

The study found that men’s breast tumors were larger at diagnosis, more advanced and more likely to have spread to other parts of the body. Men were also diagnosed later in life; in the study, they were 63 on average, versus 59 for women.

Many men have no idea that they can get breast cancer, and some doctors are in the dark, too, dismissing symptoms that would be an automatic red flag in women, said study leader Dr. Jon Greif, a breast cancer surgeon in Oakland, Calif.

The American Cancer Society estimates 1 in 1,000 men will get breast cancer, versus 1 in 8 women. By comparison, 1 in 6 men will get prostate cancer, the most common cancer in men.

“It’s not really been on the radar screen to think about breast cancer in men,” said Dr. David Winchester, a breast cancer surgeon in NorthShore University HealthSystem in suburban Chicago who was not involved in the study. Winchester treats only a few men with breast cancer each year, compared with at least 100 women.

The researchers analyzed 10 years of national data on breast cancer cases, from 1998 to 2007. A total of 13,457 male patients diagnosed during those years were included, versus 1.4 million women. The database contains about 75 percent of all U.S. breast cancer cases.

The men who were studied lived an average of about eight years after being diagnosed, compared with more than 10 years for women. The study doesn’t indicate whether patients died of breast cancer or something else.

Greif prepared a summary of his study for presentation Friday at a meeting of American Society of Breast Surgeons in Phoenix.

Dr. Akkamma Ravi, a breast cancer specialist at Weill Cornell Medical College in New York, said the research bolsters results in smaller studies and may help raise awareness. Because the disease is so rare in men, research is pretty scant, and doctors are left to treat it the same way they manage the disease in women, she said.

Some doctors said one finding in the study suggests men’s breast tumors might be biologically different from women’s: Men with early-stage disease had worse survival rates than women with early-stage cancer. But men’s older age at diagnosis also might explain that result, Greif said.

The causes of breast cancer in men are not well-studied, but some of the same things that increase women’s chances for developing it also affect men, including older age, cancer-linked gene mutations, a family history of the disease, and heavy drinking.

There are no formal guidelines for detecting breast cancer in men. The American Cancer Society says routine, across-the-board screening of men is unlikely to be beneficial because the disease is so rare.

For men at high risk because of a strong family history or genetic mutations, mammograms and breast exams may be helpful, but men should discuss this with their doctors, the group says.

Men’s breast cancer usually shows up as a lump under or near a nipple. Nipple discharge and breasts that are misshapen or don’t match are also possible signs that should be checked out.

Tom More, 67, of Custer, Wash., was showering when he felt a pea-size lump last year near his right nipple. Because a golfing buddy had breast cancer, More didn’t put off seeing his doctor. The doctor told More that he was his first male breast cancer patient.

Robert Kaitz, a computer business owner in Severna Park, Md., thought the small growth under his left nipple was just a harmless cyst, like ones that had been removed from his back. By the time he had it checked out in 2006, almost two years later, the lump had started to hurt.

The diagnosis was a shock.

“I had no idea in the world that men could even get breast cancer,” Kaitz said. He had a mastectomy, and 25 nearby lymph nodes were removed, some with cancer. Chemotherapy and radiation followed.

Tests showed Kaitz, 52, had a BRCA genetic mutation that has been linked to breast and ovarian cancer in women. He may have gotten the mutation from his mother, who is also a breast cancer survivor. It has also been linked to prostate cancer, which Kaitz was treated for in 2009.

A powerboater and motorcycle buff, Kaitz jokes about being a man with a woman’s disease but said he is not embarrassed and doesn’t mind showing his breast surgery scar.

The one thing he couldn’t tolerate was tamoxifen, a hormone treatment commonly used to help prevent breast cancer from returning in women. It can cause menopausal symptoms, so he stopped taking it.

“It killed me. I tell you what — night sweats, hot flashes, mood swings, depression. I’d be sitting in front of the TV watching a drama and the tears wouldn’t stop pouring,” he said.

Doctors sometimes prescribe antidepressants or other medication to control those symptoms.

Now Kaitz gets mammograms every year. Men need to know that “we’re not immune,” he said. “We have the same plumbing.”

AP Medical Writer Lindsey Tanner