Embracing the Pros and Cons of the New Weight Loss Medications (Semaglutide, Tirzepatide, Etc.).

PURPOSE OF REVIEW: The history of multiple weight loss medications has been a concerning paradox based on an increased cardiovascular risk despite significant reductions in adipose tissue and weight. A new class of weight loss medications could change this past narrative based on early preliminary results of cardiovascular risk (not events-still need to be determined) and weight reduction in non-diabetics that acutely competes with results achieved with bariatric surgery. The purpose of this review is to provide a comprehensive summary of the advantages and disadvantages of these newer medications, and how they could impact urology. RECENT FINDINGS: Weight loss of - 15 to - 20% compared to baseline has become plausible in the short-term and preliminary guidance to reduce acute and chronic adverse events are receiving attention. However, the cost, access, conflicts of interest, supply chain, life-long adherence issues, and the long-term diverse implications on mental and physical health when exposed to this class of medications (GLP-1 agonists) are unknown. The profound caloric reductions should also result in baseline or ongoing nutritional deficiency testing, and general and specific dietary recommendations, which could theoretically mimic some bariatric surgery pre- and post-surgical protocols but has yet to be studied. Regardless, the potential impact of these medicines within a variety of medical specialties needs clinical research. Current and future lifestyle interventions, dietary patterns, and medicines in the weight loss category need to be held to a paradigm whereby cardiovascular health should improve with significant weight loss without a negative impact on mental health. In urology, the ability to impact cancer risk, ED, FSD, incontinence, infertility, nephrolithiasis, and multiple other endpoints are plausible (based on bariatric surgery data) but need preliminary clinical research. Other medicines with a similar or even larger potential impact are in clinical trials, and thus, a concise overview for clinicians and researchers was needed for objective guidance. Currently, comprehensive lifestyle changes utilized with and without these medications continue to garner positive mental, physical, and legacy effects, which suggest that they are as necessary as ever in the treatment of the numerous conditions impacted by unhealthy weight gain.

Nutraceuticals and Phytotherapy in Men's Health: Antioxidants, Pro-oxidants, and a Novel Opportunity for Lifestyle Changes.

Patients using nutraceuticals represent a diverse patient population with a keen potential interest and/or adherence to healthy lifestyle changes. BPH nutraceuticals, including saw palmetto were as safe, but not more effective than placebo in the STEP and CAMUS clinical trials, but another high-quality saw palmetto product could be tested in a phase 3 trial. Several other BPH supplements need more recent robust clinical data, environmental oversight, or safety data. ED supplements, including Panax ginseng, and the notable nitric oxide (NO) enhancing amino acids arginine and citrulline have positive preliminary short-term efficacy data with and without PDE-5 inhibitors, but herbal quality control (QC) or safety signals with some of these agents in specific patient populations need to be resolved. "Less is more" should be the current mantra in the prostate cancer milieu, and potentially in some men with male infertility based on the FAZST trial because it is plausible some antioxidants are exhibiting prooxidant activity in some settings. Some prescription anthelmintic medications are being studied, others are being purchased over-the-counter (OTC), but their preliminary safety and efficacy against cancer have been concerning and questionable. In fairness, ongoing additional objective clinical trial data should become available soon, especially with mebendazole. DHEA or DHEA enhancing products have multiple concerns including HDL reductions, and their questionable use in men with BPH or prostate cancer based on the limited data. Some of these concerns should also be addressed in long-term robust clinical trials of prescription testosterone agents. Regardless, more attention should be directed toward heart-healthy lifestyle changes for most urologic men's health conditions, whether they are used in a preventive or synergistic setting with other acceptable clinical treatment options.

Adult preventive vaccines with other synergistic lifestyle options: is it time to add these ancillary benefits to the overall AS management checklist?

PURPOSE: To review the potential ancillary cardiovascular and other health impacts of compliance with general adult vaccination series in the prostate cancer active surveillance (AS) population. No previous review has been published in regard to this specific topic. METHODS: Literature review of PubMed data up to December 2020 RESULTS: Compliance rates for adult vaccination are in the approximate anemic range of 25-50% with occasional higher rates of specific vaccines in the elderly population including annual influenza and pneumococcal prevention. Herpes zoster (HZ) and numerous other vaccine preventive illnesses are associated with an increased risk of cardiovascular events. Preliminary evidence suggests vaccine compliance could reduce overall morbidity and mortality, and adherence to heart healthy lifestyle changes and parameters could further improve vaccine efficacy and overall wellness. COVID-19 vaccine utilization and research should also continue to reinforce the direct and ancillary benefits of this entire preventive intervention category. CONCLUSIONS: Multiple ancillary lifestyle change recommendations could be included in the AS criteria to potentially reduce morbidity and mortality in this population, and perhaps the most unsung intervention is to improve the inadequate rates of general adult vaccination compliance and other heart healthy behavioral changes that impact their efficacy. Heart health, prostate health, and immune system health are closely interlinked.

Preventing Lethal Prostate Cancer with Diet, Supplements, and Rx: Heart Healthy Continues to Be Prostate Healthy and "First Do No Harm" Part III.

PURPOSE OF REVIEW: To discuss the overall and latest observations of the effect of diet, lifestyle, supplements, preventive vaccinations, and some prescription heart healthy medications for prostate cancer prevention within a 3-part series of publications. RECENT FINDINGS: The concept of maximizing heart health to prevent aggressive prostate cancer continues to be solidified with additional prospective observational and randomized controlled trial data. Heart healthy is prostate healthy, but heart unhealthy is prostate unhealthy. The primary goal for medical providers of reducing all-cause and cardiovascular disease (CVD) morbidity and mortality correlates with maximizing prostate cancer prevention. The obesity epidemic in children and adults along with research from multiple, diverse disciplines has only strengthened the nexus between heart and prostate health. Greater dietary adherence toward a variety of healthy foods is associated with a graded reduction in the probability of CVD and aggressive cancer. Preventing prostate cancer via dietary supplements should encourage a "first do no harm" or less-is-more approach until future evidence can reverse the concerning trend that more supplementation has resulted in either no impact or an increased risk of prostate cancer. Supplements to reduce side effects of some cancer treatments appear to have more encouraging data. A discussion of quality control (QC) before utilizing any pill also requires attention. Medications or interventions that potentially improve heart health including statins, aspirin, and metformin (S.A.M.), specific beta-blocker medications, and even preventive vaccines are in general generic, low cost, "natural," and should continue to garner research interest. A watershed moment in medical education has arrived where the past perception of a diverse number of trees seemingly separated by vast distances, in reality, now appears to exist within the same forest.

Preventing Lethal Prostate Cancer with Diet, Supplements, and Rx: Heart Healthy Continues to Be Prostate Healthy and "First Do No Harm" Part II.

PURPOSE OF REVIEW: To discuss the overall and latest observations of the effect of diet, lifestyle, supplements, and some prescription heart healthy medications for prostate cancer prevention. RECENT FINDINGS: The concept of maximizing heart health to prevent aggressive prostate cancer continues to be solidified with the addition of more prospective observational and randomized controlled trial data. Heart healthy is prostate healthy, and heart unhealthy is prostate unhealthy. The primary goal of reducing the risk of all-cause and cardiovascular disease (CVD) morbidity and mortality also coincides with maximizing prostate cancer prevention. The obesity epidemic in children and adults along with recent diverse research has only strengthened the nexus between heart and prostate health. Greater dietary adherence toward a variety of healthy foods is associated with a graded improved probability of CVD and potentially aggressive cancer risk reduction. Preventing prostate cancer via dietary supplements should encourage a "first do no harm," or less is more approach until future evidence can reverse the concerning trend that more supplementation has resulted in either no impact or an increased risk of prostate cancer. Supplements to reduce side effects of some cancer treatments appear to have more encouraging data. A discussion of quality (QC) before utilizing any pill also requires attention. Medications or interventions that potentially improve heart health including statins, aspirin, and metformin (S.A.M.), specific beta-blocker medications, and even preventive vaccines are in general generic, low-cost, "natural," and should continue to garner research interest. A watershed moment in medical education has arrived where the past perception of a diverse number of trees seemingly separated by vast distances, in reality, now appear to exist within the same forest.

Correction to: Immunogenic Yeast-Based Fermentation Product Reduces Allergic Rhinitis-Induced Nasal Congestion: A Randomized, Double-Blind, Placebo-Controlled Trial.

The article ''Immunogenic Yeast-Based Fermentation Product Reduces Allergic Rhinitis-Induced Nasal Congestion: A Randomized, Double-Blind, Placebo-Controlled Trial'', written by Mark A. Moyad, Larry E. Robinson, Julie M. Kittelsrud, Stuart G. Reeves, Susan E. Weaver, Aireen I. Guzman, Mark E. Bubak was originally published electronically on the publisher's internet portal (currently Springer-Link) on 12 August, 2009.

Preventing Lethal Prostate Cancer with Diet, Supplements, and Rx: Heart Healthy Continues to Be Prostate Healthy and "First Do No Harm" Part I.

PURPOSE OF REVIEW: To discuss the overall and latest observations of the effect of diet, lifestyle, supplements, and some prescription heart healthy medications for prostate cancer prevention. RECENT FINDINGS: The concept of maximizing heart health to prevent aggressive prostate cancer continues to be solidified with the addition of more prospective observational and randomized controlled trial data. Heart healthy is prostate healthy, but heart unhealthy is prostate unhealthy. The primary goal of reducing the risk of all-cause and cardiovascular disease (CVD) morbidity and mortality also allows for maximizing prostate cancer prevention. The obesity epidemic in children and adults along with recent diverse research has only strengthened the nexus between heart and prostate health. Greater dietary adherence toward a variety of healthy foods is associated with a graded improved probability of CVD and potentially aggressive cancer risk reduction. Preventing prostate cancer via dietary supplements should encourage a "first do no harm", or less is more approach until future evidence can reverse the concerning trend that more supplementation has resulted in either no impact or an increased risk of prostate cancer. Supplements to reduce side effects of some cancer treatments appear to have more encouraging data. Medications that improve heart health including statins, aspirin, and metformin (S.A.M.), and specific beta-blocker medications are primarily generic or low-cost and should continue to garner research interest. A watershed moment in medical education has arrived where the past perception of a diverse number of trees seemingly separated by vast distances, in reality, now appear to exist within the same forest.

Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy.

Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT) use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as "prostate cancer" and "androgen deprivation therapy", "cardiovascular risk", "lean body mass", "exercise", and "diet". The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to provide effective, accessible, and relatively inexpensive strategies for mitigating ADT-associated toxicities without introducing additional adverse effects.

Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods.

Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin).

Heart healthy equals prostate healthy and statins, aspirin, and/or metformin (S.A.M.) are the ideal recommendations for prostate cancer prevention.

Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Lifestyle factors that promote CVD also appear to increase prostate cancer risk and those that reduce CVD risk also appear to reduce the risk of prostate cancer. The largest randomized trials utilizing dietary supplements or pharmacologic agents for prostate cancer prevention (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) have also shed light on the problems and future solutions in this area. Dietary supplements that have not been found to be CVD protective, such as selenium and Vitamin E have not been found to be prostate protective. In addition, over exposure to specific anti-oxidants in nutritionally replete populations may be encouraging cancer growth. Future trials of dietary supplements to prevent prostate cancer could be problematic because by the time a definitive trial is initiated the participants will no longer be "deficient" in the nutrient being tested, which arguably occurred in the SELECT trial. It is also interesting that statins, aspirin, and/or metformin (S.A.M.) are 3 generic, low-cost, heart healthy agents derived from natural sources with separate mechanism of actions, which all appear to have the best benefit to risk ratio compared to any other agent available for prostate cancer prevention, especially aggressive disease, or as an ancillary agent (s) to conventional cancer treatment. It is time to focus on the forest over the trees and recommend proven CVD protective measures for men concerned about their risk of prostate cancer.

Short-term enzalutamide treatment for the potential remission of active surveillance or intermediate-risk prostate cancer: a case study, review, and the need for a clinical trial.

Active surveillance (AS) is a widely recognized and utilized option by which prostate cancer patients with less aggressive tumors on diagnosis defer immediate traditional conventional therapy (surgery, radiation) and undergo close monitoring by a physician for any clinical or pathologic changes. The juxtaposition of low- to intermediate-risk elderly patients between effective and conventional treatment with associated risks and monitoring without the opportunity for relief of anxiety and other psychological problems can be significant. Minimal and safe treatment over 6 months with the hope of eliminating the existing disease is of significant interest to prostate cancer patients. Unfortunately, dietary supplements have failed to improve and have sometimes even contributed to disease progression. In addition, the use of multiple medications is not always appropriate or safe. In this case study, we administered low doses of enzalutamide (80 mg/day-120 mg/day) in an AS patient during a 6 month period. Results showed a significant reduction in tumor size, as evidenced by magnetic resonance imaging and color Doppler, as well as a an undetectable level of prostate specific antigen during, and immediately following treatment. The use of an oral second-generation androgen-receptor signaling inhibitor was shown to be of benefit to patients unwilling to pursue AS and conventional treatment. Administration of enzalutamide did not reduce testosterone levels, but helped maintain good quality of life, was more cost effective at low doses, and was previously shown to be heart healthy and efficacious during early stages of castration-resistant prostate cancer. Although we do not advocate enzalutamide as a treatment approach in these situations, we believe that a clinical trial to evaluate short-term low-dose treatment using enzalutamide is warranted.

What do most erectile dysfunction guidelines have in common? No evidence-based discussion or recommendation of heart-healthy lifestyle changes and/or Panax ginseng.

Sexual health or erectile dysfunction (ED) state of the art guidelines provide a thorough overview of conventional prescription or other notable extrinsic treatment options. Yet, over the past 10-15 years, a plethora of international researchers have established that individual and comprehensive lifestyle changes can prevent and potentially improve ED. We review the lifestyle evidence that should equate to grade A or level 1 evidence recommendations for ED. We also review the evidence for Panax ginseng, an over-the-counter (OTC) dietary supplement with a 35-year history of laboratory investigations, multiple positive randomized trials over approximately 15 years and several independent meta-analyses and systematic reviews. Perhaps it is time to at least discuss and even emphasize lifestyle and other non-conventional interventions in ED guidelines so that patients can explore a diversity of potentially synergistic choices with their physicians and can improve their quality and quantity of life. Ignoring the consistent, positive data on lifestyle modifications in ED guidelines, for example, is tantamount to ignoring diet and lifestyle changes to reduce the risk of or ameliorate cardiovascular diseases.

The optimal male health diet and dietary supplement program.

The primary cause of mortality in most developed countries is cardiovascular disease, which is the primary cause of death in the largest clinical studies of male health conditions. There are simplistic correlations between heart health and male-specific diseases. Clinicians need to motivate and provide a simplistic and realistic set of lifestyle, dietary supplement, and prescription drug recommendations to men to affect all-cause morbidity and mortality. This article provides recommendations to assist the clinician and patient to make practical changes that may be accomplished in a short period of time, and should provide tangible overall benefit for men's health.

Promoting wellness for patients on androgen deprivation therapy: why using numerous drugs for drug side effects should not be first-line treatment.

The controversy over androgen deprivation therapy (ADT) for prostate cancer seems to have shifted over the past decade. The issue of adverse events or side effects now seems to dominate over that of clinical efficacy. However, this article provides evidence that questions the treatment of these side effects with numerous prescription medications that have their own unique toxicity profile in patients with nonmetastatic disease. The hope is that patients will no longer be considered passive participants in the prevention and treatment of ADT side effects, now that information is available to help mitigate many of these effects.

Molecular markers that can be utilized in diet and dietary supplement research.

Prostate and other cancers have a multitude of potential markers that can be used in laboratory and clinical studies of diet and dietary supplement interventions. More overt clinical markers include imaging tests, biopsy samples, prostate-specific antigen kinetics, and urinary testing. Many molecular markers are currently available, including antiapoptotic and apoptotic proteins, cell adhesion molecules, cell cycle compounds, growth factors, angiogenic markers, and proliferative and inflammatory signals. Protein kinases and transcription factors should also be considered for diversity. Testing of numerous molecular markers has become critical in gaining preliminary insight into the potential impact of a novel diet and supplemental agents.