Thursday, 25 April 2019

Erectile dysfunction drugs may protect against penis shrinkage after prostate surgery

I take my pancreas for granted. When I eat, it pumps out insulin. This hormone helps blood sugar get into my cells. When I haven’t eaten for a while, my pancreas makes another hormone called glucagon that prevents my blood sugar from dropping too low.

People with type 1 diabetes don’t have this luxury. But someday they may, thanks to a bionic pancreas developed at Boston University and Massachusetts General Hospital.

In an early test of the device, reported online this week in the New England Journal of Medicine, it helped control blood sugar levels in 20 adults and 32 teenagers with type 1 diabetes who went about their daily lives without the constant monitoring and injecting that’s required with type 1 diabetes.

Right now, this artificial pancreas is essentially an app that runs on an iPhone wirelessly connected to a monitor worn on the abdomen that continually checks blood sugar and two pumps, one for insulin and one for glucagon.

The system work like this: The app on the phone tracks blood sugar. When blood sugar begins to rise, the app signals one pump to release insulin. If blood sugar falls too low, it signals the other pump to release glucagon. This is basically what happens in a healthy body.
Managing type 1 diabetes now and in the future

Type 1 diabetes is what’s known as an auto-immune disease. It occurs when the body mistakenly attacks and destroys healthy cells in the pancreas that make insulin and glucagon. People with type 1 diabetes must constantly check their blood sugar and give themselves insulin. Until recently, checking was done by pricking a finger and placing blood on a small strip inserted in a meter, and insulin was administered with a shot. Today, more and more people with type 1 diabetes are checking blood sugar using a sensor worn on the abdomen and delivering insulin through an implanted pump.

Researchers Edward Damiano, an associate professor of biomedical engineering at Boston University, along with Steven Russell, an assistant professor of medicine at Harvard-affiliated Massachusetts General Hospital, and other colleagues used these components to build their prototype. They have begun a second round of testing, and hope to have a more sophisticated version on the market in five years.

For Damiano, the work is personal: he as a 15-year-old son who has had type 1 diabetes since he was a baby.

Many researchers around the world are searching for a way to cure type 1 diabetes. There’s still no end in sight in that search. But the development of a bionic pancreas represents a bridge that would let people with type 1 diabetes control their blood sugar with less hassle, and more safely, than they do now. I’m not much use behind the keyboard until I’ve had my morning cup of coffee. And I’m far from the only American who needs a little java jolt to get their day going.

If a study published in this month’s Journal of Nutrition is any indication, the caffeine in coffee might offer not just a momentary mental boost but also longer-term effects on thinking skills. Having an alcoholic drink a day might also benefit our mental performance, but the line between just right and too much is uncertain. An even better strategy for maintaining memory and thinking skills with age may be to eat a healthy diet.

In the study, researchers from the National Institute on Aging compared scores on various tests of thinking skills and memory with caffeine, alcohol, and nutrient intake in 727 men and women taking part in the Baltimore Longitudinal Study of Aging. Over all, participants who ranked high on the healthy diet scale did better on 10 tests of memory than those with lower diet scores. The same held true for those who took in more caffeine. The effects for moderate alcohol drinking were mixed.
The caffeine-brain connection

The reason you get a quick wakeup call after chugging a mug of coffee has to do with the way caffeine tricks your brain. Not only is caffeine a brain stimulant, but it also blocks receptors for a chemical called adenosine, which normally prevents the release of excitatory brain chemicals. With adenosine out of the way, these brain-sparking chemicals can flow more freely—giving you a surge of energy and potentially improving mental performance and slowing age-related mental decline.

The Journal of Nutrition study isn’t the last word on the subject of caffeine and memory. It showed that people—particularly those who were ages 70 and over—who took in more caffeine scored better on tests of mental function, but not on memory tests or other measures of mental ability.

Some previous studies have shown improved long-term memory performance and thinking ability in regular caffeine consumers; others haven’t shown any connection.
Drink to your cognitive health?

When it comes to alcohol, its effects on memory and thinking skills may depend on how they are measured and how much you’re drinking. In this study, moderate alcohol use appeared to improve working memory and attention—especially in women and in those ages 70 and over. But those benefits could come at the expense of declines in skills like executive function and global thinking.

Excessive drinking, defined as more than two drinks a day for men or more than one a day for women, is known to harm the brain. Over time, excessive drinking can cause everything from short-term memory lapses to more permanent problems. Any benefits from alcohol seen in the Journal of Nutrition study came from moderate drinking.
Better memory through diet

The study also looked at the connection between diet and mental performance. People who ate foods with plenty of healthful nutrients had better attention and memory than participant with poorer diets. A healthy diet was also linked to good thinking skills in women and participants under age 70. In particular, foods that are part of the Mediterranean diet—fruits, vegetables, nuts, fish, olive oil, and whole grains—show promise for preserving memory and preventing Alzheimer’s and other forms of dementia.
A recipe for maintaining memory

This study is just one of many linking healthy eating habits with maintaining memory and thinking skills into old age. Continuing a healthy diet, or switching to one, makes sense on many levels. It probably is good for your brain, and it’s definitely good for your heart, bones, muscles, and overall health.

As for caffeine? There’s no evidence yet that you need to start drinking coffee or tea to protect your brain. If you like drinking caffeinated beverages, enjoy them. But keep in mind that adding lots of sugar or cream, or getting caffeine via sugar-sweetened soda, may counter any benefits.

What about alcohol? If you enjoy drinking alcohol, keep it moderate—or less. As the researchers write, “alcohol has potentially deleterious effects over time with lower intake being a better choice than moderate intake.” A study published in JAMA Internal Medicine in 2014 found that men who used the erection-enhancing drug sildenafil (Viagra) were 84% more likely to develop melanoma, the most dangerous form of skin cancer, over a period of 10 years.

That finding makes for an attention-grabbing headline. But it’s also what I would call a true lie: a scientifically correct statement that could easily be misunderstood to mean “that little blue pill gives you deadly skin cancer.”

Here are two truths about this work that you need to know. 1) This study does not show that Viagra causes skin cancer. Instead, it shows that in a large group of men, those who said they used Viagra ended up being diagnosed more often with melanoma than those who didn’t use this drug. The study shows a connection, not a cause. 2). Even if Viagra does promote melanoma, the absolute increase is small.

I asked an expert in melanoma and skin cancer risk at Harvard-affiliated Massachusetts General Hospital, Dr. Hensin Tsao, what he thought of the study. He kindly shot back an email offering his perspective: “This is certainly a provocative study and warrants more careful replication. Several factors need to be considered.”  Allow me to translate: The devil is in the details. The study is interesting but it does not mean that men should be worried—yet—that Viagra causes melanoma.

But they should definitely be worried about melanoma.
Risky business

The study grew out of laboratory research on how Viagra acts on cell-to-cell signaling pathways. This work demonstrated that the drug mimics key parts of a process that lets melanoma cells spread to other parts of the body. Skin cancer that spreads (metastasizes) is hard to control and can end in death.

To explore whether Viagra might have the same effect on melanoma in humans, a team of researchers looked at data collected from men taking part in the Health Professionals’ Follow-up Study, a project based at Harvard that began in 1986. The men filled out health and lifestyle questionnaires every two years. The questionnaire started asking men about use of erectile dysfunction drugs in 2000. In that year, 1,618 men reported having ever used Viagra.

Over the next decade, among the 29,929 men who said they had never used Viagra, 128 developed melanoma. Among the 1,618 Viagra users, 14 developed melanoma. In other words, 4.3 of every 1,000 who didn’t take Viagra developed melanoma compared to 8.6 of every 1,000 men who took Viagra.

After statistical adjustments, the increase from 4.3 to 8.6 is the 84% increase in risk that many news reports focused on. Researchers call that the relative risk (one group compared to another). The absolute increase, 4.3 cases per 1,000 men, represents an increase of 0.43%.

Whether a similar connection might exist between other erectile dysfunction drugs and melanoma isn’t known. In 2000, when the study was started, Viagra was the only erectile dysfunction drug on the market. Tadalafil (Cialis) and vardenafil (Levitra) weren’t approved until 2003, while avanafil (Stendra) came on the market in 2012.
How risky is that business?

The raw numbers suggest that the risk for melanoma associated with Viagra is small—one of the factors that Dr. Tsao said “need to be considered” when weighing the significance of the study. It’s even smaller than what was reported in the study because not all of the 14 cancers in the Viagra group can be attributed to the drug. Many factors affect a man’s risk of melanoma—the most important of which are age and cumulative exposure to ultraviolet (UV) radiation.
Should you worry?

Should men who use Viagra worry about getting melanoma? Right now, no one can say. The relationship could be pure coincidence. Epidemiological studies like this one tell you only who is at the scene of the crime, not who done it. The findings of the JAMA Internal Medicine study need to be replicated in other groups of men before sounding any warning bells.

In the meantime, Dr. Tsao offers some urgent advice to men: Protect your skin from too much sun and have routine skin checks to identify melanoma and other types of skin cancer early, while they are still treatable.

That’s especially important for older men, who are at greater risk for developing melanoma and also at greater risk for dying from it. An estimated 76,000 Americans (more than half of them men) will be diagnosed with melanoma this year, and almost 10,000 will die from it.

In short, be afraid—but not of Viagra. Be concerned about getting too much sun and pay attention to weird-looking moles that could turn into metastatic cancer. Cover up when you go outside, and use a broad-spectrum sunscreen liberally when you do go out into the sun to work and play. Does size matter? When the issue is penis size, many men would answer yes. So even the possibility that radical prostatectomy (an operation to remove a cancerous prostate gland) could shorten the penis is understandably troubling to men who face that operation. The true effect isn’t known: some studies have reported a temporary shortening of the penis averaging at most a half-inch or so after prostate removal surgery, while others have reported no change in penis size.

Now one of the largest investigations to date, published in a May 2014 supplement to BJU International, has found that while some men do end up with a slightly shorter penis after radical prostatectomy, taking a low dose of an erectile dysfunction drug like sildenafil (Viagra) or tadalafil (Cialis) every day or a higher dose twice a week might prevent that from happening. The take-away point? Having erections after surgery may preserve penis size, possibly by increasing blood flow.

“It’s becoming increasingly clear that having erections—and the consequent improvement in the oxygenation of penile tissues—helps improve sexual rehabilitation after prostate cancer surgery,” says Dr. Marc B. Garnick, a clinical professor of medicine at Harvard Medical School, an oncologist at Beth Israel Deaconess Medical Center, and editor in chief of Harvard Medical School’s Annual Report on Prostate Diseases. “The current study shows that routine use of an erectile dysfunction drug is helpful in this respect.”

Investigators from the Memorial Sloan Kettering Cancer Center in New York City recruited  118 volunteers to participate in the study. All were getting ready to undergo prostate removal surgery. A male nurse measured each man’s flaccid penis before the operation, and then again at two and six months after the operation.

Roughly half of the men experienced no change in penis length. Most of the rest lost about one-tenth of an inch (2.5 millimeters) in length, but had recovered to their pre-surgery size by six months. A small group of men—roughly 5%—had a persistent loss of at least one-third of an inch (one centimeter). Of these, the men who took an erectile dysfunction drug every day (which is increasingly recommended as part of post-prostatectomy care) were back to their pre-surgery sizes within six months, while those who didn’t take an erectile dysfunction drug continued to have slightly smaller penises than before the surgery.

According to the researchers, the shortening was minimal “and almost certainty not clinically meaningful,” meaning that it probably had no effect on sexual intercourse or a partner’s satisfaction.
Causes unclear

It isn’t clear how prostate removal surgery might shorten the penis. One possible explanation is that nerve injury during the operation causes muscles in and around the penis to contract. That idea is supported by earlier studies showing that efforts to spare nerves during surgery can protect against penis shrinkage.

The new study has some advantages over earlier ones. It followed the volunteers for longer than most earlier studies. In addition, all of the measurements were made by just one nurse, while earlier studies often used several nurses. That helped minimize the possibility of inter-observer variability. But there were also problems with the study, especially that half of the men who volunteered didn’t follow through and have all of the post-prostatectomy measurements.

Shortening of the penis can happen with other prostate cancer treatments beside prostatectomy. Some men who have radiation therapy or hormone therapy notice it, too. The results of the Memorial Sloan Kettering study support the idea that men should counseled about potential losses in penis size from prostate cancer treatment and be encouraged to take an erectile dysfunction drug to keep it from happening.

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