Testosterone replacement therapy ups stroke risk in men

Ageing men with low testosterone levels who take testosterone replacement therapy (TRT) are at a greater risk of experiencing an ischemic stroke or a cardiac arrest especially during the first two years of use, warn researchers.

The findings confirm concerns voiced by many health agencies about the potential risks associated with the treatment.

“Our findings show that the use of TRT was associated with an increased risk of stroke, transient ischemic attack or cardiac arrest during the first two years of use,” said a researcher.

According to researchers, there is limited evidence on the long-term clinical benefits of testosterone replacement therapy (TRT) to effectively treat the modestly declining levels of endogenous testosterone levels of aging but healthy men.

“We strongly recommend that clinicians proceed with caution when considering prescribing TRT and first discuss both the potential benefits and risks with patients,” the Dr. said.

The study analysed a large database of electronic medical records of patients enrolled in primary care practices in the UK and formed a cohort of 15,401 men, aged 45 years or older, with low testosterone levels (hypogonadism).

Users of TRT had a 21 per cent greater risk of cardiovascular events compared with non-users, corresponding to an additional 128 events.

The increased risk appears to be transient, declining after two years of TRT use, which the investigators attribute to a phenomenon called “depletion of susceptible”.

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Brain Study May Lead to New Ways to Control Pain without Opioids

Scientists say they have identified how the brain's natural painkilling system could be used as a possible alternative to opioids for the effective relief of chronic pain, which affects as many as one in three people at some point in their lives. 

The team, pinpointed an area of the brain that is important for endogenous analgesia—the brain's intrinsic pain relief system. They believe their study, could lead to the development of pain treatments that activate the painkilling system by stimulating this area of the brain, but without the dangerous side effects of opioids. 

“Tonic pain after injury characterizes a behavioural state that prioritizes recovery. Although generally suppressing cognition and attention, tonic pain needs to allow effective relief learning to reduce the cause of the pain. Here, we describe a central learning circuit that supports learning of relief and concurrently suppresses the level of ongoing pain. We used computational modelling of behavioural, physiological and neuroimaging data in two experiments in which subjects learned to terminate tonic pain in static and dynamic escape-learning paradigms,” write the investigators.

“In both studies, we show that active relief-seeking involves a reinforcement learning process manifest by error signals observed in the dorsal putamen. Critically, this system uses an uncertainty ('associability') signal detected in pregenual anterior cingulate cortex that both controls the relief learning rate, and endogenously and parametrically modulates the level of tonic pain. The results define a self-organizing learning circuit that reduces ongoing pain when learning about potential relief.”

Opioid drugs such as oxycodone, hydrocodone, and fentanyl hijack the endogenous analgesia system, which is what makes them such effective painkillers. However, they are also highly addictive, which has led to the opioid crisis in some countries, where drug overdose is now the leading cause of death for those under 50, with opioid overdoses representing two-thirds of those deaths. 

"We're trying to understand exactly what the endogenous analgesia system is: why we have it, how it works, and where it is controlled in the brain," said the Dr., who led the research. "If we can figure this out, it could lead to treatments that are much more selective in terms of how they treat pain."

"Pain can actually help us recover by removing our drive to do unnecessary things—in a sense, this can be considered 'healthy pain'. So why might the brain want to turn down the pain signal sometimes?"

The team thought that sometimes this "healthy pain" could be a problem, especially if we could actively do something that might help—such as try and find a way to cool a burn. In these situations, the brain might activate the pain-killing system to actively look for relief. To prove this, and to try and identify where in the brain this system was activated, the team designed a pair of experiments using brain-scanning technology. 

In the first experiment, the researchers attached a metal probe to the arm of a series of healthy volunteers and heated it up to a level that was painful, but not enough to physically burn them. The volunteers then played a type of gambling game where they had to find which button on a small keypad cooled down the probe. The level of difficulty was varied over the course of the experiments—sometimes it was easy to turn the probe off, and sometimes it was difficult. Throughout the task the volunteers frequently rated their pain, and the researchers constantly monitored their brain activity.

The results found that the level of pain the volunteers experienced was related to how much information there was to learn in the task. When the subjects were actively trying to work out which button they should press, pain was reduced. But when the subjects knew which button to press, it wasn't. The researchers found that the brain was actually computing the benefits of actively looking for and remembering how they got relief and using this to control the level of pain. 

Knowing what this signal should look like, the researchers then searched the brain to see where it was being used. The second experiment identified the signal in a single region of the prefrontal cortex, called the pregenual cingulate cortex. 

"These results build a picture of why and how the brain decides to turn off pain in certain circumstances, and identify the pregenual cingulate cortex as a critical 'decision center' controlling pain in the brain," said the Dr.

This decision center is a key place to focus future research efforts. In particular, the researchers are now trying to understand what the inputs are to this brain region, if it is stimulated by opioid drugs, what other chemical messenger systems it uses, and how it could be turned on as a treatment for patients with chronic pain.

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Living with a dog might make you happier

A study has found that having dog as a companion could reduce anxiety and increase happiness. In the US, most households have dogs and some studies have shown that dogs can foster cardiovascular health, resistance to stress, social connectivity and enhanced longevity. 

A path-breaking study done by researcher Erika Friedmann in 1980 showed that living with a dog lowers blood pressure, cholesterol and triglycerides. Some other studies have revealed that older people who walk dogs are more likely to be fit than those who do not walk with dog. 

Dr Friedmann, a professor at the University of Maryland School of Nursing, conducted some controlled studies to show a lower level of physiological arousal from stress-inducing situations when a friendly animal was present. 

As a study published in 2007 in Society & Animals concluded, pets "ameliorate some determinants of mental health such as loneliness." In a survey of 339 residents of Western Australia, the researchers found dog ownership to be associated "with social interactions, favour exchanges, civic engagement, perceptions of neighbourhood friendliness and sense of community." 

Alan M Beck, who heads the Center for the Human-Animal Bond at Purdue, said that people must carefully consider the implications before deciding to have a dog as pet. "Look for an animal of an appropriate breed, size and temperament for your household," he said.

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Novel way to treat retinal blindness soon

In a ray of hope for people at the risk of retinal blindness, identifying ways to leverage our immune system to clean out abnormal blood vessels in the retina may lead to treatments that could prevent or delay blindness or even restore sight.

Scientists have discovered that the body's innate immune system does more than help ward off external pathogens.

It also helps remove sight-robbing abnormal blood vessels while leaving healthy cells and tissue intact.

This discovery is significant as the retina is part of the central nervous system and its cells cannot be replaced once lost.

“Our findings identify a new role of the innate immune system by which endogenous mediators selectively target the pathologic retinal vasculature for removal,” explained Kip M. Connor, a researcher from Harvard Medical School and Massachusetts eye and ear infirmary angiogenesis laboratory in Boston, Massachusetts.

"This insight would help develop therapies that result in a greater visual outcome and quality of life for patients suffering from diabetic retinopathy or retinopathy of prematurity,” Connor added.

Connor and colleagues compared two groups of mice: a genetically-modified group which lacked activity in the innate immune complement system and a normal group with a fully functional innate immune system.

Researchers placed both groups in an environment that induced irregular blood vessel growth in the eye, mimicking what happens in many human ocular diseases.

In the normal mice, scientists were able to visualise the immune system targeting and killing only the irregular blood vessels while leaving healthy cells unharmed.

Knowing how the complement system works to keep our retinas clean is an important first-step toward new treatments that could mimic this activity, said Gerald Weissmann, editor-in-chief of the FASEB Journal which carried the study.

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