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Study Solves Testosterone’s Paradoxical Effects in Prostate Cancer

The AHA! Team — Mon, 30 Sep 2024 08:33:27 +0000

Duke Health – A treatment paradox has recently come to light in prostate cancer: Blocking testosterone production halts tumor growth in early disease, while elevating the hormone can delay disease progression in patients whose disease has advanced. The inability to understand how different levels of the same hormone can drive different effects in prostate tumors has been an impediment to the development of new therapeutics that exploit this biology. Now, a Duke Cancer Institute-led study, performed in the laboratory of Donald McDonnell, Ph.D. and appearing this week in Nature Communications, provides the needed answers to this puzzle. The researchers found that prostate cancer cells are hardwired with a system that allows them to proliferate when the levels of testosterone are very low. But when hormone levels are elevated to resemble those present in the normal prostate, the cancer cells differentiate. “For decades, the goal of endocrine therapy in prostate cancer has been to achieve absolute inhibition of androgen receptor function, the protein that senses testosterone levels,” said lead investigator Rachid Safi, Ph.D., research assistant professor in the Department of Pharmacology and Cancer Biology, at Duke University School of Medicine. “It’s been a highly effective strategy, leading to substantial improvements in overall survival,” he said. “Unfortunately, most patients with advanced, metastatic disease who are treated with drugs to inhibit androgen signaling will progress to an aggressive form of the disease for which there are limited therapeutic options.” Using a combination of genetic, biochemical, and chemical approaches, the research team defined the mechanisms that enable prostate cancer cells to recognize and respond differently to varying levels of testosterone, the most common androgenic hormone. It turned out to be rather simple. When androgen levels are low, the androgen receptor is encouraged to “go solo” in the cell. In doing so, it activates the pathways that cause cancer cells to grow and spread. However, as androgens rise, the androgen receptors are forced to “hang out as a couple,” creating a form of the receptor that halts tumor growth. “Nature has designed a system where low doses of hormones stimulate cancer cell proliferation and high doses cause differentiation and suppress growth, enabling the same hormone to perform diverse functions,” McDonnell said. In recent years, clinicians have begun treating patients with late-stage, therapy resistant prostate cancers using a monthly, high-dose injection of testosterone in a technique called bi-polar androgen therapy, or BAT. The inability to understand how this intervention works has hindered its widespread adoption as a mainstream therapeutic approach for prostate cancer patients. “Our study describes how BAT and like approaches work and could help physicians select patients who are most likely to respond to this intervention,” McDonnell said. “We have already developed new drugs that exploit this new mechanism and are bringing these to the clinic for evaluation as prostate cancer therapeutics.” In addition to McDonnell and Safi, study authors include Suzanne E. Wardell, Paige Watkinson, Xiaodi Qin, Marissa Lee, Sunghee Park, Taylor Krebs, Emma L. Dolan, Adam Blattler, Toshiya Tsuji, Surendra Nayak, Marwa Khater, Celia Fontanillo, Madeline A. Newlin, Megan L. Kirkland, Yingtian Xie, Henry Long, Emma Fink, Sean W. Fanning, Scott Runyon, Myles Brown, Shuichan Xu, Kouros Owzar, and John D. Norris. The study received funding support from the National Cancer Institute (R01-CA271168, P30CA014236) and the North Carolina Biotechnology Center. To read the original article click here.

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Low-Fat Diet Associated With Reduction in Testosterone Among Men

AHA Publisher — Sun, 12 Jan 2020 08:00:54 +0000

Wolters Kluwer via News-Medical Net – For the many men diagnosed with testosterone deficiency, losing weight can help increase testosterone levels. But certain diets – specifically a low-fat diet – may be associated with a small but significant reduction in testosterone. The study was published in The Journal of Urology®, Official Journal of the American Urological Association (AUA). The Journal is published in the Lippincott portfolio by Wolters Kluwer. “We found that men who adhered to a fat restrictive diet had lower serum testosterone than men on a nonrestrictive diet,” according to the report by Jake Fantus, MD, of the Section of Urology, Department of Surgery, University of Chicago Medicine and colleagues from the Department of Urology, Northwestern University Feinberg School of Medicine, and the Department of Surgery, NorthShore University Health System. “However,” the researchers add, “the clinical significance of small differences in serum T across diets is unclear.” Best Diet for Low Testosterone? No Single Right Answer Yet Dr. Fantus and colleagues analyzed data on more than 3,100 men from a nationwide health study (the National Health and Nutrition Examination Survey, or NHANES). All participants had available data on diet and serum testosterone level. Based on two-day diet history, 14.6 percent of men met criteria for a low-fat diet, as defined by the American Heart Association (AHA). Another 24.4 percent of men followed a Mediterranean diet high in fruits, vegetables, and whole grains but low in animal protein and dairy products. Only a few men met criteria for the AHA low-carbohydrate diet, so this group was excluded from the analysis. The average serum testosterone level was 435.5 ng/dL (nanograms per deciliter). Serum testosterone was lower in men on the two restrictive diets: average 411 ng/dL for those on a low-fat diet and 413 ng/dL for those on the Mediterranean diet. The associations were adjusted for other factors that can affect testosterone, including age, body mass index, physical activity, and medical conditions. After adjustment, the low-fat diet was significantly associated with reduced serum testosterone, although the Mediterranean diet was not. Overall, 26.8 percent of men had testosterone levels less than 300 ng/dL. Despite the difference in average testosterone levels, the proportion of men with low testosterone was similar across all diet groups. Low testosterone is highly prevalent in the United States, as approximately 500,000 men are diagnosed with testosterone deficiency each year. Testosterone deficiency can lead to problems, including decreased energy and libido, along with physiological alterations, including increased body fat and reduced bone mineral density. In addition to medications, treatment for low testosterone often includes lifestyle modifications, such as exercise and weight loss. But the effects of diet on testosterone levels have been unclear. Because testosterone is a steroid hormone derived from cholesterol, changes in fat intake could alter testosterone levels. This new analysis of how diet affects serum testosterone provides evidence that a low-fat diet is associated with lower testosterone levels, compared to an unrestricted diet. So what diet is best for men with testosterone deficiency? The answer remains unknown, according to the authors. In overweight or obese men, the health benefits of a low-fat diet likely far exceed the small reduction in serum testosterone. In contrast, for men who are not overweight, avoiding a low-fat diet “may be a reasonable component” of a multifaceted approach to increasing serum testosterone. Dr. Fantus and coauthors note that further studies will be needed to corroborate their findings, and to clarify the mechanism by which restrictive diets reduce testosterone. But due to the difficulties of large-scale dietary studies, definitive trials are unlikely to be performed. “Therefore, our data represent a valuable approach towards answering this important question,” the authors conclude. To read the original article click here.

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5 Facts to Know About Testosterone and Aging in Modern Times

AHA Publisher — Wed, 18 Sep 2019 05:22:46 +0000

Dr. Don Colbert – Low testosterone affects many men, both under and over 60 years old, and is becoming an increasingly diagnosed condition. There are many factors that affect testosterone and aging, and some declines are due to modern, sedentary lifestyles and environmental pollutants. Aging has a lot of effects on the human body. Some are positive, and some are not as positive. One effect that gets a lot of attention in men is the natural decline of testosterone. And while this is a natural part of the aging process, there are some concerning facts about modern-day lifestyle that may expedite and exaggerate the decline. What’s more, there are mortality-linked health conditions associated with low testosterone in addition to the hormonal and sexual challenges. Here’s your guide to testosterone, and 5 facts to know about testosterone and aging in modern times. What Is Testosterone? Testosterone is an androgen hormone produced by the testicles. The hypothalamus and pituitary gland control how much testosterone the testes produce and secrete. Testosterone is responsible for the development of male sexual characteristics. Females also produce testosterone, but in small amounts than males. In males, testosterone is believed to regulate and balance many functions including: • sperm count and development of mature sperm • sex drive • fat distribution • bone mass • muscle size and strength • red blood cell production In females, it also contributes to sex drive, bone density, and muscle strength. But, too much can be a bad thing for women. Excessive levels can cause women to experience male pattern baldness and infertility (1). 5 Facts to Know About Testosterone and Aging in Modern Times 1. Testosterone Naturally Declines With Age After 40 Years Part of the natural aging process includes a decline in testosterone. Typically, this slow decline is not cause for extreme interventions, but it is concerning for many men. It is known as late-onset hypogonadism. In fact, after the age of 40, the concentration of circulating testosterone declines by about 1.6% every year for typical males (2). After about 20 years of decline, testosterone levels are low enough that they would be diagnosed as hypogonadism in a younger man. Unfortunately, the current rate of hypogonadism in 45-year-old males is about 40% and climbing. In those who are 60 years or older, the diagnosis of low testosterone has increased by 170% since 2012 (3). But why? 2. Beyond Aging, Many Factors Can Cause Low Testosterone In addition to natural aging, many factors contribute to declining testosterone. Causes can include: • testicular injury • infection of the testicles • medications • chronic diseases, including type 2 diabetes, kidney and liver disease, obesity, and HIV/AIDS • genetic diseases • disorders that affect the hormones, such as pituitary tumors or high prolactin levels • Long life expectancy (many men are getting tested at later ages) If these are the origin of a decline, the cause should be treated instead of, or along with, the symptoms. 3. There Is Concern About Modern Men’s Testosterone Levels Studies have found that the current levels of testosterone circulating in modern men are lower than generations past for the same age. This has been found in studies in the United States, Netherlands, and Australia, among other locations worldwide (4). In fact, low testosterone is becoming more and more common. Prescriptions for testosterone supplements and medications has increased fivefold since 2012 (5). There are many hypotheses regarding the cause of the generational decline in testosterone. These include: • Increased obesity (6) • Increased use of medications • Indoor, sedentary lifestyles • Lack of physical activity • Too much endurance-level activity • Environmental pollutants including pesticides • Chemical exposure including BPA’s, chemicals in coolants, and antibacterial agents that mimic estrogens (7) 4. Low Testosterone Can Result in Both Sexual Dysfunction and Major Health Problems Low testosterone after age 60, or late-onset hypogonadism, has become a recognized medical condition. However, many of its symptoms are associated with normal aging. These symptoms include (8): • diminished erectile quality, particularly at night • decreased libido • mood changes • reduced cognitive function • fatigue (9) • a decrease in muscle mass and strength • decreased body hair • skin changes • decreased bone mass and bone mineral density • increase in abdominal fat mass Unfortunately, low testosterone is also associated with higher mortality and chronic disease. It’s sort of a vicious cycle. Chronic disease can cause low testosterone, and low testosterone may also bring on conditions such as depression, cardiovascular disease, metabolic disease, and more (10). 5. Treatments Are Available But Not All Created Equal Low Testosterone is a real problem for many men, whether due to natural aging or medical causes. What can be done? First, there are lifestyle changes to make including: • Weight loss using Keto Zone • More Outside Activity • Reversal of High Blood Sugars and Diabetes Using Keto Zone • Addition of Resistance and Weight-Bearing Exercise • Decrease in Medications • A decrease in exposure to pesticides and pollutants Of course, these lifestyle changes are great for full-body health, but they may not bring on quick results for testosterone levels. For years, researchers and doctors have also weighed the benefits of Testosterone Replacement Therapy. While older men with clinically low testosterone often respond well to it, there may be significant side effects to consider. Also, there’s inconclusive evidence that it is helpful and safe in younger men. Bottom Line Low testosterone affects many men, both under and over 60 years old, and is becoming an increasingly diagnosed condition. There are many factors that affect testosterone and aging, and some declines are due to modern, sedentary lifestyles and environmental pollutants. But there is good news on the horizon. With Keto Zone, overweight men and those at risk of diabetes can improve testosterone through weight loss and improved blood sugars. There is also hope for new, natural formulations in the future to help with testosterone and aging in modern times. To read the original article click here. For more articles by Dr. Colbert click here.

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