Abstract
Background:
Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men.
Objective:
To establish harmonized reference ranges for total testosterone in men ...that can be applied across laboratories by cross-calibrating assays to a reference method and standard.
Population:
The 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; and Male Sibling Study of Osteoporosis.
Methods:
Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at Centers for Disease Control and Prevention (CDC). Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were used to generate harmonized values, which were used to derive standardized, age-specific reference ranges.
Results:
Harmonization procedure reduced intercohort variation between testosterone measurements in men of similar ages. In healthy nonobese men, 19 to 39 years, harmonized 2.5th, 5th, 50th, 95th, and 97.5th percentile values were 264, 303, 531, 852, and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men.
Conclusion:
Harmonized normal range in a healthy nonobese population of European and American men, 19 to 39 years, is 264 to 916 ng/dL. A substantial proportion of intercohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator.
We cross-calibrated cohort-specific assays to a reference method at CDC and generated harmonized reference ranges for circulating testosterone levels in men, including age-adjusted reference ranges.
OBJECTIVES
To develop an evidence‐based definition of sarcopenia that can facilitate identification of older adults at risk for clinically relevant outcomes (eg, self‐reported mobility limitation, ...falls, fractures, and mortality), the Sarcopenia Definition and Outcomes Consortium (SDOC) crafted a set of position statements informed by a literature review and SDOC's analyses of eight epidemiologic studies, six randomized clinical trials, four cohort studies of special populations, and two nationally representative population‐based studies.
METHODS
Thirteen position statements related to the putative components of a sarcopenia definition, informed by the SDOC analyses and literature synthesis, were reviewed by an independent international expert panel (panel) iteratively and voted on by the panel during the Sarcopenia Position Statement Conference. Four position statements related to grip strength, three to lean mass derived from dual‐energy x‐ray absorptiometry (DXA), and four to gait speed; two were summary statements.
RESULTS
The SDOC analyses identified grip strength, either absolute or scaled to measures of body size, as an important discriminator of slowness. Both low grip strength and low usual gait speed independently predicted falls, self‐reported mobility limitation, hip fractures, and mortality in community‐dwelling older adults. Lean mass measured by DXA was not associated with incident adverse health‐related outcomes in community‐dwelling older adults with or without adjustment for body size.
CONCLUSION
The panel agreed that both weakness defined by low grip strength and slowness defined by low usual gait speed should be included in the definition of sarcopenia. These position statements offer a rational basis for an evidence‐based definition of sarcopenia. The analyses that informed these position statements are summarized in this article and discussed in accompanying articles in this issue of the journal. J Am Geriatr Soc 68:1410‐1418, 2020.
See related editorial by Cesari et al in this issue
Abstract
Recent research has unveiled an expansive role of NAD+ in cellular energy generation, redox reactions, and as a substrate or cosubstrate in signaling pathways that regulate health span and ...aging. This review provides a critical appraisal of the clinical pharmacology and the preclinical and clinical evidence for therapeutic effects of NAD+ precursors for age-related conditions, with a particular focus on cardiometabolic disorders, and discusses gaps in current knowledge. NAD+ levels decrease throughout life; age-related decline in NAD+ bioavailability has been postulated to be a contributor to many age-related diseases. Raising NAD+ levels in model organisms by administration of NAD+ precursors improves glucose and lipid metabolism; attenuates diet-induced weight gain, diabetes, diabetic kidney disease, and hepatic steatosis; reduces endothelial dysfunction; protects heart from ischemic injury; improves left ventricular function in models of heart failure; attenuates cerebrovascular and neurodegenerative disorders; and increases health span. Early human studies show that NAD+ levels can be raised safely in blood and some tissues by oral NAD+ precursors and suggest benefit in preventing nonmelanotic skin cancer, modestly reducing blood pressure and improving lipid profile in older adults with obesity or overweight; preventing kidney injury in at-risk patients; and suppressing inflammation in Parkinson disease and SARS-CoV-2 infection. Clinical pharmacology, metabolism, and therapeutic mechanisms of NAD+ precursors remain incompletely understood. We suggest that these early findings provide the rationale for adequately powered randomized trials to evaluate the efficacy of NAD+ augmentation as a therapeutic strategy to prevent and treat metabolic disorders and age-related conditions.
Graphical Abstract
Graphical Abstract
Among men receiving androgen-deprivation therapy for prostate cancer, there is a high frequency of the metabolic syndrome and an increased risk of cardiovascular death. How the loss of anabolic ...signals leads to sarcopenia and metabolic abnormalities may be informative.
The
Clinical Implications of Basic Research
series has focused on highlighting laboratory research that could lead to advances in clinical therapeutics. However, the path between the laboratory and the bedside runs both ways: clinical observations often pose new questions for laboratory investigations that then lead back to the clinic. The first of a series of occasional articles drawing attention to the bedside-to-bench flow of information is presented here, under the
Basic Implications of Clinical Observations
rubric. We hope our readers will enjoy these stories of discovery, and we invite them to submit their own examples of clinical findings that have . . .
Bhasin discusses testosterone replacement in aging men. The deluge of advertisements marketing erectile dysfunction medications and testosterone products has empowered many older men to seek medical ...help for their sexual and genitourinary problems. As a reflection of this historical transition toward increased attention on men's sexual health, men's health clinics have sprung up across the US; concomitantly, testosterone prescription sales increased from about $100 million US dollars in the year 2000 to nearly $2.7 billion in 2013. Testosterone levels decline gradually with advancing age after peaking in the second and third decades of life. Genetic factors, adiposity, and comorbid conditions affect the trajectory of age-related decline in testosterone levels.
Diagnosis and treatment of hypogonadism in men Bhasin, Shalender; Basaria, Shehzad
Best Practice & Research Clinical Endocrinology & Metabolism,
04/2011, Letnik:
25, Številka:
2
Journal Article
Recenzirano
Androgen deficiency is diagnosed by ascertainment of characteristic signs and symptoms and consistently low testosterone levels, measured preferably in the morning using a reliable assay. The ...clinical presentation of androgen deficiency varies with the age of its onset, genetic factors, prior treatment, and other host factors. Androgen deficiency can be treated using any one of the approved testosterone formulations after consideration of pharmacokinetics, patient preference, cost, and potential formulation-specific adverse effects. Prostate and breast cancer, erythrocytosis, untreated severe obstructive sleep apnea, congestive heart failure, recent myocardial infarction, and severe lower urinary tract symptoms are contraindications for testosterone therapy. Testosterone therapy should be accompanied by a standardized monitoring plan that includes periodic ascertainment of symptomatic improvement and lower urinary tract symptoms, measurements of testosterone level, hematocrit, and PSA, digital prostate examination, and general health evaluation. While the benefit to risk ratio is generally favorable in healthy young men with classical hypogonadism due to diseases of the testes, pituitary and the hypothalamus, neither the clinical benefits of testosterone therapy on patient-important outcomes nor its long-term risks in older men with age-related decline in testosterone level are known.
The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and ...aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.
Context: The risks of testosterone therapy in men remain poorly understood.
Objective: The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate ...the adverse effects of testosterone treatment in men.
Data Sources: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies.
Study Selection: Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility.
Data Extraction: Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data.
Data Synthesis: The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14 and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, −0.49 mg/dl; 95% CI, −0.85 to −0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes.
Conclusions: The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.
Current evidence suggests that testosterone use in men causes erythrocytosis, but evidence about cardiovascular events and prostate outcomes is limited and imprecise.
Physical performance measures, including cardiopulmonary exercise testing (CPXT), are widely used in geriatric practice and aging research. Theoretically, research participants and study personnel ...could get infected in the closed environment of the exercise laboratory by contact with respiratory droplets from an infected person, by breathing virus‐laden aerosols, or by touching fomites. Older adults are at increased risk of developing more severe disease and of dying from SARS‐CoV‐2 infection. This special article offers guidance—informed by a synthesis of scientific data and recommendations of the CDC and WHO—on procedures that can be implemented in exercise laboratories to minimize risk of SARS‐CoV‐2 and other respiratory infections. Most tests of physical function (e.g., gait speed, Short Physical Performance Battery) are not aerosol‐generating and are associated with only a small increase in minute ventilation; in contrast, CPXT markedly increases minute ventilation and is potentially aerosol‐generating. Researchers should evaluate the benefit‐to‐risk ratio of information gained from the laboratory assessment versus the risk of SARS‐CoV2 infection. Risk mitigation strategies described here fall into four categories: personal hygiene and the use of personal protective equipment; standardized screening; reconfiguration of laboratory space; and optimization of laboratory ventilation. The proposed safety measures are not intended to replace institutional policy, state, or federal guidelines; they may not apply to all settings and are expected to evolve as more definitive information becomes available. These practical measures to maximize protection against SARS‐CoV2 infection can help maximize participant and staff safety, reduce anxiety, and facilitate protocol adherence, and study integrity.
See related Letter by Tamara Konetzka et al. and Special article Cohen et al.
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