Hormone Treatment for Prostate Cancer Linked to Heightened Alzheimer’s Risk

E.J. Mundell wrote . . . . . . . . .

Soon after a man is diagnosed with prostate cancer, drugs that lower levels of testosterone are often offered as treatment, since testosterone fuels the cancer’s growth.

But a major new study suggests that this approach might have an unwanted side effect: Higher odds for Alzheimer’s disease and other dementias.

“Our results suggest that clinicians need to raise their awareness about potential long-term cognitive effects of hormone therapy and discuss these risks with their patients,” said study author Ravishankar Jayadevappa.

He’s a research associate professor of geriatrics at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.

One expert said it does raise troubling questions.

“Most of us are becoming as afraid of getting Alzheimer’s as we are of getting cancer,” said Dr. Elizabeth Kavaler, a urology specialist at Lenox Hill Hospital in New York City. “When a study pits one debilitating condition against another, it instills fear in patients.”

But the treatment — called androgen-deprivation therapy — remains the “gold standard” for many cases of prostate cancer, according to Kavaler. Therefore, the new data means “tough decision-making” for patients and their physicians, she said.

In the new study, Jayadevappa’s group took a look back at U.S. National Cancer Institute data on over 154,000 prostate cancer patients who were diagnosed between 1996 and 2003. About 62,000 received hormone-depleting therapy within two years of their diagnosis, while about 92,000 did not.

In total, 13% of men who had received the therapy went on to develop Alzheimer’s disease over eight years of follow-up, compared to 9% who hadn’t gotten the treatment, the study found. According to the researchers, the lifetime prevalence of Alzheimer’s disease in men generally is about 12%.

When the team looked at diagnoses of all forms of dementia, 22% of those who’d received the therapy received such a diagnosis, compared to 16% of those who hadn’t undergone hormonal therapy.

Jayadevappa’s team noted that earlier, smaller studies have found similar trends.

However, “to our knowledge, this is one of the largest studies to date examining this association, and it followed patients for an average of eight years after their prostate cancer diagnosis,” he said in a university news release.

As the researchers noted, androgen-deprivation therapy is an effective means of slowing the progress of prostate cancers. However, it is now typically only used in cases of advanced disease, or cases where the chances of a tumor recurrence are high.

The approach also has other deleterious side effects, including impaired sexual function, and potential harm to bones and cardiovascular health.

The study also can only point to an association between hormonal treatment and raised odds for dementia, it cannot prove cause and effect. But Jayadevappa’s team noted that they tried to account for other factors, such as age, the presence of other medical conditions and the severity of the prostate cancer.

Dr. Maria Torroella Carney is chief of geriatric and palliative medicine at Northwell Health in New Hyde Park, N.Y. Looking over the findings, she said they warrant further study, but it’s not time for men who’ve gotten hormonal therapy to panic.

Carney stressed that the study couldn’t prove cause and effect, and other factors might account for the higher risk of dementia.

Men receiving hormonal therapy tended to be “older, sicker and had more advanced prostate cancer,” Carney noted, and sicker patients already have higher odds of dementia.

In addition, the study didn’t reveal whether or not men who got the therapy lived longer than those who didn’t. If they did live longer, their odds of dementia would also increase over time, Carney explained.

Study co-author Dr. Thomas Guzzo agreed that no one should make rash decisions on prostate cancer care based on this study alone.

“I think we need to look at these patients on an individual level,” said Guzzo, who is chief of urology at the University of Pennsylvania. “Certainly, there are patients who need hormonal therapy and benefit from it greatly,” he said in a university news release. “There are others where the evidence is less clear, and in these patients, we should consider the risk of hormonal therapy versus the benefit in treating their prostate cancer. This should be a shared decision-making process with the patient.”

The study was published online in JAMA Network Open.

Source: HealthDay


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Study: Most Testosterone-boosting Supplements Are Ineffective

Elyse Blye wrote . . . . . . . . .

Men who want to improve their libido or build body mass may want to think twice before using testosterone-boosting supplements ­— also known as “T boosters” — as research shows these alternatives to traditional testosterone replacement therapy may not have ingredients to support their claims, according to Mary K. Samplaski, MD, assistant professor of clinical urology at the Keck School of Medicine of USC.

“Many supplements on the market merely contain vitamins and minerals, but don’t do anything to improve testosterone,” Samplaski said. “Often, people can be vulnerable to the marketing component of these products, making it difficult to tease out what is myth and what is reality.”

Testosterone is the primary male sex hormone and the reason why men produce sperm and have Adam’s apples. It’s also why men develop more “masculine” features like bulging muscles, a deep voice, broad shoulders and a hairy chest. After age 30, most men experience a gradual decline in testosterone, sometimes causing these features to diminish or new symptoms to occur, like erectile dysfunction. In an attempt to turn back the hands of time, some men will turn to T boosters.

Using a structured review approach, Samplaski and a team of researchers explored the active ingredients and advertised claims of 50 T boosting supplements. Their findings were published as an original article in The World Journal of Men’s Health.

Researchers performed a Google search with the search term “Testosterone Booster,” thus mimicking a typical internet research for someone looking to increase testosterone levels, and then selected the first 50 products that came up in their search. Then, the team reviewed published scientific literature on testosterone and the 109 components found in the supplements. Zinc, fenugreek extract and vitamin B6 were three of the most common components in the supplements.

The team also compared the content for each supplement with the Food and Drug Administration’s (FDA) Recommended Daily Allowance (RDA) and the upper tolerable intake level (UL) as set by the Institute of Medicine of the National Academy of Sciences.

Of the 150 supplements, researchers came across 16 general claims to benefit patients, including claims to “boost T or free T”, “build body lean mass or muscle mass”, or “increase sex drive or libido.”

While 90% of the T booster supplements claimed to boost testosterone, researchers found that less than 25% of the supplements had data to support their claims. Many also contained high doses of vitamins and minerals, occasionally more than the tolerable limit.

Unlike drugs, supplements are not intended to treat, diagnose, prevent, or cure diseases, according to the FDA. As such, Samplaski would like to see more regulation around testosterone-boosting supplements to protect consumers. She also would like to explore disseminating handouts to her patients with more accurate information in the hopes that it encourages patients to seek a medical professional for low testosterone issues.

While no one can escape the effects of aging, Samplaski said there is something men can do to address their concerns. “The safest and most effective way for men to boost low testosterone levels is to talk with a medical professional or a nutritionist.”

Source: University of Southern California


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Exercise and Hormones: 8 Hormones Involved in Exercise

Pete McCall wrote . . . . . . . . .

In the movie Fletch, released the same year that ACE was founded (1985), comedian Chevy Chase plays the role of Irwin “Fletch” Fletcher, a reporter working undercover to expose drug dealing on the beaches of Los Angeles. Over the course of his investigation, Fletch assumes a variety of creative characters as he identifies the corrupt businessmen and cops involved in the drug-dealing ring. In one scene, Fletch pretends to be an airplane mechanic and tries to fib his way into a hangar by saying he was there to check the ball bearings. “It’s all ball bearings nowadays,” is one of the most memorable quotes of this iconic ‘80s movie.

If you work as a personal trainer or group fitness instructor you have no doubt been asked how exercise can help someone achieve a specific goal. If you want a fun, but honest way to answer these questions, you can channel your inner Fletch by replying, “It’s all hormones nowadays.”

The endocrine system regulates the production of hormones, which are chemicals that control cellular functions. Hormones can affect a number of different cells; however, they only influence the ones with specific receptor sites. Hormones control a number of physiological reactions in the body including energy metabolism, reproductive processes, tissue growth, hydration levels, synthesis and degradation of muscle protein, and mood. Hormones are responsible for both building new muscle and helping to burn fat, so it is important to have an understanding of which ones are released in relation to exercise as well as understanding the physiological functions they influence.

There are three major classifications of hormones: steroid, peptide and amines (modified amino acid hormones). Each class of hormones has a unique chemical structure that determines how it interacts with specific receptors. Steroid hormones interact with receptors in the nucleus of a cell, peptide hormones are comprised of amino acids and work with specific receptors sites on the cell membrane, and amines contain nitrogen and influence the sympathetic nervous system.

Hormones can either be anabolic, which means they help build new tissue, or catabolic because they play a role in breaking tissue down. The term “anabolic steroids” is often mentioned as a method of cheating used by athletes who want to improve performance; however, anabolic steroids are actually natural chemicals produced by the body that are responsible for promoting tissue growth.

Listed below are some important exercise and hormones along with the physiological functions they control.

Insulin

A peptide hormone produced by the pancreas, insulin regulates carbohydrate and fat metabolism. When blood sugar is elevated, insulin is released to promote the storage and absorption of glycogen and glucose. Insulin helps reduce levels of glucose in the blood by promoting its absorption from the bloodstream to skeletal muscles or fat tissues. It is important to know that insulin can cause fat to be stored in adipose tissue instead of being used to fuel muscle activity. When exercise starts, the sympathetic nervous system suppresses the release of insulin; consequently, it is important to avoid foods with high levels of sugar (including sports drinks) before exercise because it can elevate insulin levels and promote glycogen storage instead of allowing it to be used to fuel physical activity. Wait until the body has started sweating before using any sports drinks or energy gels.

Glucagon

Released in response to low levels of blood sugar, glucagon is produced by the pancreas to stimulate the release of free fatty acids (FFAs) from adipose tissue and increase blood glucose levels, both of which are important for fueling exercise activity. As glycogen levels are depleted during exercise, glucagon releases additional glycogen stored in the liver.

Cortisol

Cortisol is a catabolic steroid hormone produced by the adrenal gland in response to stress, low blood sugar and exercise. It supports energy metabolism during long periods of exercise by facilitating the breakdown of triglyceride and protein to create the glucose necessary to help fuel exercise. Cortisol is released when the body experiences too much physical stress or is not sufficiently recovered from a previous workout. While cortisol helps promote fat metabolism, exercising for too long can elevate levels of cortisol to catabolize muscle protein for fuel instead of conserving it to be used to repair damaged tissues.

Epinephrine and Norepinephrine

These amine hormones play an important role in helping the sympathetic nervous system (SNS) produce energy and in regulating the body’s function during cardiorespiratory exercise. Classified as catecholamines, epinephrine and norepinephrine are separate but related hormones. Epinephrine, often referred to as adrenaline because it is produced by the adrenal gland, elevates cardiac output, increases blood sugar (to help fuel exercise), promotes the breakdown of glycogen for energy and supports fat metabolism. Norepinephrine performs a number of the same functions as epinephrine, while also constricting blood vessels in parts of the body not involved in exercise.

Testosterone

Testosterone is a steroid hormone produced by the Leydig cells of the testes in males and the ovaries of females, with small amounts produced by the adrenal glands of both genders. Testosterone is responsible for muscle protein resynthesis and the repair of muscle proteins damaged by exercise, and plays a significant role in helping grow skeletal muscle. Testosterone works with specific receptor sights and is produced in response to exercise that damages muscle proteins.

Human Growth Hormone

Human growth hormone (HGH) is an anabolic peptide hormone secreted by the anterior pituitary gland that stimulates cellular growth. Like all hormones, HGH works with specific receptor sites and can produce a number of responses, including increasing muscle protein synthesis responsible for muscle growth, increasing bone mineralization, supporting immune system function and promoting lipolysis, or fat metabolism. The body produces HGH during the REM cycles of sleep and is stimulated by high-intensity exercise such as heavy strength training, explosive power training or cardiorespiratory exercise at or above the onset of blood lactate (OBLA, the second ventilatory threshold).

Insulin-like Growth Factor

Insulin-like growth factor (IGF) has a similar molecular structure to insulin and is stimulated by the same mechanisms that produce HGH. IGF is a peptide hormone produced in the liver and supports the function of HGH to repair protein damaged during exercise, which makes it an important hormone for promoting muscle growth.

Brain-derived Neurotrophic Factor

Brain-derived neurotrophic factor (BDNF) is a neurotransmitter that helps stimulate the production of new cells in the brain. The production of BDNF is closely related to the production of HGH and IGF—the same exercises that elevate levels of those hormones also increase amounts of BDNF. High-intensity exercise can stimulate anabolic hormones for muscle growth while elevating levels of BDNF, which can help improve cognitive function.

Understanding how exercise influences the hormones that control physiological functions can assist you in developing effective exercise programs for your clients. Hormones have both short- and long-term responses to exercise. In the acute phase immediately post-exercise, testosterone (T), HGH and IGF are produced to repair damaged tissue. Over the long-term, there is an increase in the receptor sites and binding proteins, which allow T, HGH and IGF to be used more effectively for tissue repair and muscle growth. For clients who want muscle growth, the levels of T, HGH and IGF are produced in response to the amount of mechanical stress created during resistance-training exercises. Moderate to heavy loads performed until momentary fatigue generate high levels of mechanical force, which creates more damage to muscle protein, which signals the production of T, HGH and IGF to repair protein, which results in muscle growth.

While there are a myriad of hormones responsible for an almost infinite number of physiological functions, the hormones listed above are directly influenced by physical activity and play important roles in helping the body adapt to the imposed physical demands of exercise. Many fitness professionals understand that the nervous and muscular systems play important roles in determining the outcomes of an exercise program. However, the reality is that hormones influence many of the physiological adaptations to physical activity. That means that, “It’s all hormones nowadays,” is the appropriate response to many questions about how the human body responds to exercise.

Source: American Council on Exercise


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Ghrelin – the Hunger Hormone

Ghrelin is a hormone that is produced and released mainly by the stomach with small amounts also released by the small intestine, pancreas and brain.

Ghrelin has numerous functions. It is termed the ‘hunger hormone’ because it stimulates appetite, increases food intake and promotes fat storage. When administered to humans, ghrelin increases food intake by up to 30%; it circulates in the bloodstream and acts at the hypothalamus, an area of the brain crucial in the control of appetite. Ghrelin has also been shown to act on regions of the brain involved in reward processing such as the amygdala.

Ghrelin also stimulates the release of growth hormone from the pituitary gland, which, unlike ghrelin itself, breaks down fat tissue and causes the build-up of muscle.

Ghrelin also has protective effects on the cardiovascular system and plays a role in the control of insulin release.

How is ghrelin controlled?

Ghrelin levels are primarily regulated by food intake. Levels of ghrelin in the blood rise just before eating and when fasting, with the timing of these rises being affected by our normal meal routine. Hence, ghrelin is thought to play a role in mealtime ‘hunger pangs’ and the need to begin meals. Levels of ghrelin increase when fasting (in line with increased hunger) and are lower in individuals with a higher body weight compared with lean individuals, which suggests ghrelin could be involved in the long-term regulation of body weight.

Eating reduces concentrations of ghrelin. Different nutrients slow down ghrelin release to varying degrees; carbohydrates and proteins restrict the production and release of ghrelin to a greater extent than fats.

Somatostatin also restricts ghrelin release, as well as many other hormones released from the digestive tract.

What happens if I have too much ghrelin?

Ghrelin levels increase after dieting, which may explain why diet-induced weight loss can be difficult to maintain. One would expect higher levels in people with obesity. However, ghrelin levels are usually lower in people with higher body weight compared with lean people, which suggests ghrelin is not a cause of obesity; although there is a suggestion that obese people are actually more sensitive to the hormone. However, more research is needed to confirm this.

Prader-Willi syndrome is a genetic disease in which patients have severe obesity, extreme hunger and learning difficulties. Unlike more common forms of obesity, circulating ghrelin levels are high in Prader-Willi syndrome patients and start before the development of obesity. This suggests that ghrelin may contribute to their increased appetite and body weight.

Ghrelin levels are also high in cachexia and the eating disorder, anorexia nervosa. This may be the body’s way of making up for weight loss by stimulating food intake and fat storage.

What happens if I have too little ghrelin?

Gastric bypass surgery, which involves reducing the size of the stomach, is considered to be the most effective treatment for severe, life-threatening obesity. Patients who lose weight after bypass surgery have been found to have lower ghrelin levels than those who lose weight by other means such as diet and exercise, which may partly explain the long-lasting success of this treatment.

Source: Society for Endocrinology

Growth Hormone, Athletic Performance, and Aging

Can human growth hormones really benefit aging, like the elusive fountain of youth? In 1513, the Spanish explorer Juan Ponce de Len arrived in Florida to search for the fountain of youth. If he got any benefit from his quest, it was due to the exercise involved in the search.

Few men today believe in miraculous waters, but many, it seems, believe in the syringe of youth. Instead of drinking rejuvenating waters, they inject human growth hormone to slow the tick of the clock. Some are motivated by the claims of the “anti-aging” movement, others by the examples of young athletes seeking a competitive edge. Like Ponce de Len, the athletes still get the benefit of exercise, while older men may use growth hormone shots as a substitute for working out. But will growth hormone boost performance or slow aging? And is it safe?

What is human growth hormone?

Growth hormone (GH) is a small protein that is made by the pituitary gland and secreted into the bloodstream. GH production is controlled by a complex set of hormones produced in the hypothalamus of the brain and in the intestinal tract and pancreas.

The pituitary puts out GH in bursts; levels rise following exercise, trauma, and sleep. Under normal conditions, more GH is produced at night than during the day. This physiology is complex, but at a minimum, it tells us that sporadic blood tests to measure GH levels are meaningless since high and low levels alternate throughout the day. But scientists who carefully measure overall GH production report that it rises during childhood, peaks during puberty, and declines from middle age onward.

GH acts on many tissues throughout the body. In children and adolescents, it stimulates the growth of bone and cartilage. In people of all ages, GH boosts protein production, promotes the utilization of fat, interferes with the action of insulin, and raises blood sugar levels. GH also raises levels of insulin-like growth factor-1 (IGF-1).

Human growth hormone benefits

GH is available as a prescription drug that is administered by injection. GH is indicated for children with GH deficiency and others with very short stature. It is also approved to treat adult GH deficiency — an uncommon condition that almost always develops in conjunction with major problems afflicting the hypothalamus, pituitary gland, or both. The diagnosis of adult GH deficiency depends on special tests that stimulate GH production; simple blood tests are useless at best, misleading at worst.

Adults with bona fide GH deficiencies benefit from GH injections. They enjoy protection from fractures, increased muscle mass, improved exercise capacity and energy, and a reduced risk of future heart disease. But there is a price to pay. Up to 30% of patients experience side effects that include fluid retention, joint and muscle pain, carpal tunnel syndrome (pressure on the nerve in the wrist causing hand pain and numbness), and high blood sugar levels.

HGH doping and athletic performance

Adults who are GH deficient get larger muscles, more energy, and improved exercise capacity from replacement therapy. Athletes work hard to build their muscles and enhance performance. Some also turn to GH.

It’s not an isolated problem. Despite being banned by the International Olympic Committee, Major League Baseball, the National Football League, and the World Anti-Doping Agency, GH abuse has tainted many sports, including baseball, cycling, and track and field. Competitive athletes who abuse GH risk disqualification and disgrace. What do they gain in return? And do they also risk their health?

Because GH use is banned and athletic performance depends on so many physical, psychological, and competitive factors, scientists have been unable to evaluate GH on the field. But they can conduct randomized clinical trials that administer GH or a placebo to healthy young athletes and then measure body composition, strength, and exercise capacity in the lab.

A team of researchers from California conducted a detailed review of 44 high-quality studies of growth hormone in athletes. The subjects were young (average age 27), lean (average body mass index 24), and physically fit; 85% were male. A total of 303 volunteers received GH injections, while 137 received placebo.

After receiving daily injections for an average of 20 days, the subjects who received GH increased their lean body mass (which reflects muscle mass but can also include fluid mass) by an average of 4.6 pounds. That’s a big gain — but it did not translate into improved performance. In fact, GH did not produce measurable increases in either strength or exercise capacity. And the subjects who got GH were more likely to retain fluid and experience fatigue than were the volunteers who got the placebo.

If you were a jock in high school or college, you’re likely to wince at the memory of your coach barking “no pain, no gain” to spur you on. Today, athletes who use illegal performance-enhancing drugs risk the pain of disqualification without proof of gain.

Human growth hormone and aging

To evaluate the safety and efficacy of GH in healthy older people, a team of researchers reviewed 31 high-quality studies that were completed after 1989. Each of the studies was small, but together they evaluated 220 subjects who received GH and 227 control subjects who did not get the hormone. Two-thirds of the subjects were men; their average age was 69, and the typical volunteer was overweight but not obese.

The dosage of GH varied considerably, and the duration of therapy ranged from two to 52 weeks. Still, the varying doses succeeded in boosting levels of IGF-1, which reflects the level of GH, by 88%.

As compared to the subjects who did not get GH, the treated individuals gained an average of 4.6 pounds of lean body mass, and they shed a similar amount of body fat. There were no significant changes in LDL (“bad”) cholesterol, HDL (“good”) cholesterol, triglycerides, aerobic capacity, bone density, or fasting blood sugar and insulin levels. But GH recipients experienced a high rate of side effects, including fluid retention, joint pain, breast enlargement, and carpal tunnel syndrome. The studies were too short to detect any change in the risk of cancer, but other research suggests an increased risk of cancer in general and prostate cancer in particular.

HGH, or simple diet and exercise?

“Every man desires to live long,” wrote Jonathan Swift, “but no man would be old.” He was right, but the fountain of youth has proved illusory. GH does not appear to be either safe or effective for young athletes or healthy older men. But that doesn’t mean you have to sit back and let Father Time peck away at you. Instead, use the time-tested combination of diet and exercise. Aim for a moderate protein intake of about .36 grams per pound of body weight; even big men don’t need more than 65 grams (about 2 ounces) a day, though athletes and men recovering from illnesses or surgery might do well with about 20% more. Plan a balanced exercise regimen; aim for at least 30 minutes of moderate exercise, such as walking, a day, and be sure to add strength training two to three times a week to build muscle mass and strength. You’ll reduce your risk of many chronic illnesses, enhance your vigor and enjoyment of life, and — it’s true — slow the tick of the clock.

Source: Harvard Medical School