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1.
Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications.
Pataky, MW, Young, WF, Nair, KS
Mayo Clinic proceedings. 2021;(3):788-814
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Abstract
Increased life expectancy combined with the aging baby boomer generation has resulted in an unprecedented global expansion of the elderly population. The growing population of older adults and increased rate of age-related chronic illness has caused a substantial socioeconomic burden. The gradual and progressive age-related decline in hormone production and action has a detrimental impact on human health by increasing risk for chronic disease and reducing life span. This article reviews the age-related decline in hormone production, as well as age-related biochemical and body composition changes that reduce the bioavailability and actions of some hormones. The impact of hormonal changes on various chronic conditions including frailty, diabetes, cardiovascular disease, and dementia are also discussed. Hormone replacement therapy has been attempted in many clinical trials to reverse and/or prevent the hormonal decline in aging to combat the progression of age-related diseases. Unfortunately, hormone replacement therapy is not a panacea, as it often results in various adverse events that outweigh its potential health benefits. Therefore, except in some specific individual cases, hormone replacement is not recommended. Rather, positive lifestyle modifications such as regular aerobic and resistance exercise programs and/or healthy calorically restricted diet can favorably affect endocrine and metabolic functions and act as countermeasures to various age-related diseases. We provide a critical review of the available data and offer recommendations that hopefully will form the groundwork for physicians/scientists to develop and optimize new endocrine-targeted therapies and lifestyle modifications that can better address age-related decline in heath.
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Personalized approach to growth hormone replacement in adults.
van Bunderen, CC, Glad, C, Johannsson, G, Olsson, DS
Archives of endocrinology and metabolism. 2019;(6):592-600
Abstract
Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality. Today, GHRT has been shown to decrease or reverse the negative effects of GHD. In addition, recent papers have shown that mortality and morbidity are approaching normal in hypopituitary patients with GHD who receive modern endocrine therapy including GHRT. Since the first dose-finding studies, it has been clear that efficacy and side effects differ substantially between patients. Many factors have been suggested as affecting responsiveness, such as sex, age, age at GHD onset, adherence, and GH receptor polymorphisms, with sex and sex steroid replacement having the greatest impact. Therefore, the individual tailoring of GH dose is of great importance to achieve sufficient efficacy without side effects. One group that stands out is women receiving oral estrogen replacement, who needs the highest dose. Serum insulin-like growth factor-1 (IGF-1) is still the most used biochemical biomarker for GH dose titration, although the best serum IGF-1 target is still debated. Patients with GHD due to acromegaly, Cushing's disease, or craniopharyngioma experience similar effects from GHRT as others. Arch Endocrinol Metab. 2019;63(6):592-600.
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Pharmacological management of osteoporosis in postmenopausal women: The current state of the art.
Gatti, D, Fassio, A
Journal of population therapeutics and clinical pharmacology = Journal de la therapeutique des populations et de la pharmacologie clinique. 2019;(4):e1-e17
Abstract
Osteoporosis is a common disease that increases fracture risk. Fragility fractures bring heavy consequences in terms of mortality and disability, with burdensome health and social costs. In subjects with clinical bone fragility, the first goal is to identify the secondary forms of osteoporosis, especially in young subjects, in males and in patients who recently experienced a fragility fracture. In addition, before considering any sort of treatment, it is fundamental to check for adequate calcium and vitamin D intake, since their deficiency is the most common reason for drug failure.In the last decade of the 20th century, several molecules have been developed and proved to be effective in achieving the true goal of any antiosteoporotic drug: fracture prevention.In this article, we considered the most commonly prescribed antiresorptive drugs (hormonal therapy, bisphosphonates, and denosumab), the anabolic agents (teriparatide), the dual-action drugs (romosozumab), and the drugs characterized by an unclear mechanism of action (strontium ranelate) to provide physicians with useful insights for their clinical practice. We discussed the main criteria for the appropriate choice selection and management of each treatment. Finally, we addressed the current controversies related to treatment discontinuation, sequential, and combination therapy.
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4.
Menopause research in Latin America.
Tserotas, K, Blümel, JE
Climacteric : the journal of the International Menopause Society. 2019;(1):17-21
Abstract
For 15 years, the Collaborative Group for Research of the Climacteric in Latin America (REDLINC) has been conducting research on several topics including age of menopause, metabolic syndrome, quality of life and climacteric symptoms, sexual dysfunction, poor quality of sleep and insomnia, and use of menopausal hormone therapy (MHT) in the general population and among gynecologists. Examples of data to have emerged for this region include the age of menopause (49 years), a high prevalence of metabolic syndrome (42.9%), and a new waist circumference cut-off value for the Latin American population (88 cm). Sexual dysfunction, poor quality of life, and sleep disorders have a prevalence of over 50%, with obesity and sedentary lifestyles affected importantly. MHT use is still low (12.5%), lack of prescription the most important reason for not using it, and gynecologists use MHT for themselves but do not recommend it often to their patients. The prevalence of alternative therapy use, recommended by physicians, is high.
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Physical exercise, nutrition and hormones: three pillars to fight sarcopenia.
Sgrò, P, Sansone, M, Sansone, A, Sabatini, S, Borrione, P, Romanelli, F, Di Luigi, L
The aging male : the official journal of the International Society for the Study of the Aging Male. 2019;(2):75-88
Abstract
BACKGROUND Sarcopenia is a pathophysiological condition diffused in elderly people; it represents a social issue due to the longer life expectancy and the growing aging population. It affects negatively quality of life and it represents a risk factor for other pathologies, such as diabetes, cardiovascular disease, and obesity. No silver bullet exists to hinder sarcopenia, but it may be counteracted by physical exercise, nutrition, and a proper endocrine milieu. Indeed, we aim to analyze the scientific literature to give to clinician effective advices to counteract sarcopenia. Main text: Physical exercise, proper nutrition, optimized hormonal homeostasis represent the three pillars to fight sarcopenia. Physical exercise represents the most effective remedy to face sarcopenia, in particular if it is combined with a proper diet and with an adequate endocrine milieu. Consistency in training, adequate daily protein intake and eugonadism seems to be the keys to fight sarcopenia. The combination of these three pillars might act synergistically. CONCLUSIONS Optimization of these factors may increase their efficiency; however, scientific data may be sometimes confusing so far. Therefore, we aim to give practical advices to clinician to identify and to highlight the most important aspects in each of these three factors that should be addressed.
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Potential application of testosterone replacement therapy as treatment for obesity and type 2 diabetes in men.
Fink, J, Matsumoto, M, Tamura, Y
Steroids. 2018;:161-166
Abstract
Sedentary lifestyle and over-nutrition are the main causes of obesity and type 2 diabetes (T2D). However, the same causes are major triggers of hypogonadism. Many T2D patients show low testosterone levels while hypogonadal men seem to be prone to become diabetic. Testosterone plays a major role in the regulation of muscle mass, adipose tissue, inflammation and insulin sensitivity and is therefore indirectly regulating several metabolic pathways, while T2D is commonly triggered by insulin resistance, increased adipose tissue and inflammation, showing a negative correlation between testosterone levels and T2D. Testosterone replacement therapy (TRT) is widely used in patients with symptoms of hypogonadism, however it is not commonly used as preventive intervention or treatment for T2D patients even though hypogonadal patients share many common symptoms (obesity, insulin insensitivity, increased inflammation, decrease in muscle mass and strength) with T2D patients. Even though TRT is often associated with side effects such as prostatic hypertrophy or cancer, cardiovascular risks due to increase in the number of red blood cells and infertility, several studies have shown that TRT remains a potent intervention improving metabolic functions such as glycated haemoglobin, blood sugar, total cholesterol and visceral fat. The purpose of this review is to discuss the possible benefits and risks of TRT in the prevention and treatment of obesity and T2D and assess the health risks and benefits of common T2D medications and testosterone.
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7.
Primary Adrenal Insufficiency: Managing Mineralocorticoid Replacement Therapy.
Esposito, D, Pasquali, D, Johannsson, G
The Journal of clinical endocrinology and metabolism. 2018;(2):376-387
Abstract
CONTEXT Mineralocorticoid (MC) replacement therapy in patients with primary adrenal insufficiency (PAI) was introduced more than 60 years ago. Still, there are limited data on how MC substitution should be optimized, because MC dosing regimens have only been systematically investigated in a few studies. We review the management of current standard MC replacement therapy in PAI and its plausible impact on outcome. DESIGN Using PubMed, we conducted a systematic review of the literature from 1939 to 2017, with the following keywords: adrenal insufficiency, MC deficiency, aldosterone, cardiovascular disease, hypertension, and heart failure. RESULTS The current standard treatment consists of fludrocortisone (FC) given once daily in the morning, aiming at normotension, normokalemia, and plasma renin activity in the upper normal range. Available data suggest that patients with PAI may be underreplaced with FC as symptoms and signs indicating chronic MC underreplacement, such as salt craving and postural dizziness persist, in many treated patients with PAI. Data acquired from large registry-based studies show that glucocorticoid doses for replacement in PAI are higher than those estimated from endogenous production. Glucocorticoid overreplacement may reduce the need of MC replacement but may also be a consequence of inadequate MC replacement. CONCLUSIONS The commonly used MC replacement in PAI may not be adequate in some patients. Insufficient MC substitution may be responsible for poor cardiometabolic outcome and the failure to restore well-being adequately in patients with PAI. Well-designed studies oriented at optimizing MC replacement therapy are urgently needed.
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8.
Quality of Life in Hypoparathyroidism.
Vokes, TJ
Endocrinology and metabolism clinics of North America. 2018;(4):855-864
Abstract
Patients with hypoparathyroidism have a multitude of physical, emotional, and cognitive complaints consistent with reduced quality of life (QOL). Impaired QOL in patients treated with conventional therapy with calcium and active vitamin D has been documented in epidemiologic (registry) studies, case-controlled studies, and surveys, and at baseline in clinical trials of parathyroid hormone (PTH). Treatment with PTH has been shown to improve QOL in some but not all studies.
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9.
Erythrocytosis Following Testosterone Therapy.
Ohlander, SJ, Varghese, B, Pastuszak, AW
Sexual medicine reviews. 2018;(1):77-85
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Abstract
INTRODUCTION A rapid increase in awareness of androgen deficiency has led to substantial increases in prescribing of testosterone therapy (TTh), with benefits of improvements in mood, libido, bone density, muscle mass, body composition, energy, and cognition. However, TTh can be limited by its side effects, particularly erythrocytosis. This review examines the literature on testosterone-induced erythrocytosis and polycythemia. AIM: To review the available literature on testosterone-induced erythrocytosis, discuss possible mechanisms for pathophysiology, determine the significance of formulation, and elucidate potential thromboembolic risk. METHODS A literature review was performed using PubMed for articles addressing TTh, erythrocytosis, and polycythemia. MAIN OUTCOME MEASURES Mechanism, pharmacologic contribution, and risk of testosterone-induced erythrocytosis. RESULTS For men undergoing TTh, the risk of developing erythrocytosis compared with controls is well established, with short-acting injectable formulations having the highest associated incidence. Potential mechanisms explaining the relation between TTh and erythrocytosis include the role of hepcidin, iron sequestration and turnover, erythropoietin production, bone marrow stimulation, and genetic factors. High blood viscosity increases the risk for potential vascular complications involving the coronary, cerebrovascular, and peripheral vascular circulations, although there is limited evidence supporting a relation between TTh and vascular complications. CONCLUSION Short-acting injectable testosterone is associated with greater risk of erythrocytosis compared with other formulations. The mechanism of the pathophysiology and its role on thromboembolic events remain unclear, although some data support an increased risk of cardiovascular events resulting from testosterone-induced erythrocytosis. Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis Following Testosterone Therapy. Sex Med Rev 2018;6:77-85.
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10.
Alternatives to Testosterone Therapy: A Review.
Lo, EM, Rodriguez, KM, Pastuszak, AW, Khera, M
Sexual medicine reviews. 2018;(1):106-113
Abstract
INTRODUCTION Although testosterone therapy (TTh) is an effective treatment for hypogonadism, recent concerns regarding its safety have been raised. In 2015, the US Food and Drug Administration issued a warning about potential cardiovascular risks resulting from TTh. Fertility preservation is another reason to search for viable alternative therapies to conventional TTh, and in this review we evaluate the literature examining these alternatives. AIMS To review the role and limitations of non-testosterone treatments for hypogonadism. METHODS A literature search was conducted using PubMed to identify relevant studies examining medical and non-medical alternatives to TTh. Search terms included hypogonadism, testosterone replacement therapy, testosterone therapy, testosterone replacement alternatives, diet and exercise and testosterone, varicocele repair and testosterone, stress reduction and testosterone, and sleep apnea and testosterone. MAIN OUTCOME MEASURES Review of peer-reviewed literature. RESULTS Medical therapies examined include human chorionic gonadotropins, aromatase inhibitors, and selective estrogen receptor modulators. Non-drug therapies that are reviewed include lifestyle modifications including diet and exercise, improvements in sleep, decreasing stress, and varicocele repair. The high prevalence of obesity and metabolic syndrome in the United States suggests that disease modification could represent a viable treatment approach for affected men with hypogonadism. CONCLUSIONS These alternatives to TTh can increase testosterone levels and should be considered before TTh. Lo EM, Rodriguez KM, Pastuszak AW, Khera M. Alternatives to Testosterone Therapy: A Review. Sex Med Rev 2018;6:106-113.