Effects of Testosterone Treatment in Older Men Snyder, Peter J; Bhasin, Shalender; Cunningham, Glenn R ...
The New England journal of medicine,
02/2016, Letnik:
374, Številka:
7
Journal Article
Recenzirano
Odprti dostop
In this study, men 65 years of age or older with low serum testosterone and symptoms of hypoandrogenism received testosterone or placebo for a year. Testosterone had a moderate benefit in sexual ...function and some benefit in mood but no benefit in vitality or walking distance.
Testosterone concentrations in men decrease with increasing age.
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Many symptoms and conditions similar to those that are caused by low testosterone levels in men with pituitary or testicular disease become more common with increasing age. Such symptoms include decreases in mobility, sexual function, and energy. These parallels suggest that the lower testosterone levels in older men may contribute to these conditions.
Previous trials of testosterone treatment in men 65 years of age or older, however, have yielded equivocal results. Although testosterone treatment consistently increased muscle mass and decreased fat mass,
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effects on physical performance,
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sexual function, . . .
Shaping the Future of Probiotics and Prebiotics Cunningham, Marla; Azcarate-Peril, M. Andrea; Barnard, Alan ...
Trends in microbiology (Regular ed.),
08/2021, Letnik:
29, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Recent and ongoing developments in microbiome science are enabling new frontiers of research for probiotics and prebiotics. Novel types, mechanisms, and applications currently under study have the ...potential to change scientific understanding as well as nutritional and healthcare applications of these interventions. The expansion of related fields of microbiome-targeted interventions, and an evolving landscape for implementation across regulatory, policy, prescriber, and consumer spheres, portends an era of significant change. In this review we examine recent, emerging, and anticipated trends in probiotic and prebiotic science, and create a vision for broad areas of developing influence in the field.
An expanding range of candidate probiotic species and prebiotic substrates is emerging to address newly elucidated data-driven microbial niches and host targets.Overlapping with, and adjacent to, the probiotic and prebiotic fields, new variants of microbiome-modulating interventions are developing, including synbiotics, postbiotics, microbial consortia, live biotherapeutic products, and genetically modified organisms, with renewed interest in polyphenols, fibres, and fermented foods.Personalised nutrition and precision medicine are beginning to influence the application of probiotics and prebiotics, with growing interest in modulation of microbial signatures of health and disease.Demand for probiotics and prebiotics across divergent product formats is driving innovation in quality assurance techniques to measure dose, viability, and structural and functional integrity.
Abstract
Objective
To update the “Testosterone Therapy in Men With Androgen Deficiency Syndromes” guideline published in 2010.
Participants
The participants include an Endocrine Society–appointed ...task force of 10 medical content experts and a clinical practice guideline methodologist.
Evidence
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.
Consensus Process
One group meeting, several conference calls, and e-mail communications facilitated consensus development. Endocrine Society committees and members and the cosponsoring organization were invited to review and comment on preliminary drafts of the guideline.
Conclusions
We recommend making a diagnosis of hypogonadism only in men with symptoms and signs consistent with testosterone (T) deficiency and unequivocally and consistently low serum T concentrations. We recommend measuring fasting morning total T concentrations using an accurate and reliable assay as the initial diagnostic test. We recommend confirming the diagnosis by repeating the measurement of morning fasting total T concentrations. In men whose total T is near the lower limit of normal or who have a condition that alters sex hormone–binding globulin, we recommend obtaining a free T concentration using either equilibrium dialysis or estimating it using an accurate formula. In men determined to have androgen deficiency, we recommend additional diagnostic evaluation to ascertain the cause of androgen deficiency. We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and of monitoring therapy and involving the patient in decision making. We recommend against starting T therapy in patients who are planning fertility in the near term or have any of the following conditions: breast or prostate cancer, a palpable prostate nodule or induration, prostate-specific antigen level > 4 ng/mL, prostate-specific antigen > 3 ng/mL in men at increased risk of prostate cancer (e.g., African Americans and men with a first-degree relative with diagnosed prostate cancer) without further urological evaluation, elevated hematocrit, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within the last 6 months, or thrombophilia. We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations, taking into consideration patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost. Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.
This update to the Endocrine Society’s 2010 testosterone guideline, prepared by an expert panel, describes the diagnosis, screening, treatment, and monitoring of hypogonadal men.
Objective: Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006.
Participants: The Task Force was ...composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration.
Conclusions: We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected by measurement of free or bioavailable testosterone level, using validated assays. We recommend testosterone therapy for men with symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 4 ng/ml or greater than 3 ng/ml in men at high risk for prostate cancer such as African-Americans or men with first-degree relatives with prostate cancer without further urological evaluation, hematocrit greater than 50%, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score above 19, or uncontrolled or poorly controlled heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient’s preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.
The 2010 update of the Endocrine Society guideline for the evaluation and treatment of androgen deficiency syndromes in adult men, published previously in 2006, is presented.
Context: Symptoms and signs consistent with androgen deficiency and low testosterone levels are recognized frequently in clinical practice. Recent population-based epidemiological studies indicate ...that low testosterone levels in men are associated with increased morbidity and mortality. The clinician must be able to counsel patients to help them determine whether testosterone replacement therapy is appropriate for them.
Evidence Acquisition: The authors have conducted a literature search in PubMed, and we have reviewed references in the multiple systematic reviews and meta-analyses that have been published on this topic.
Evidence Synthesis: We have attempted to provide the reader with an appreciation of the evidence that can be used to support the diagnosis of androgen deficiency, the efficacy of treatment, the potential risks of treatment, the therapeutic options, and the recommendations for monitoring treatment.
Conclusions: We think that published clinical experience justifies testosterone replacement therapy in males who have not initiated puberty by age 14 and in males with low testosterone levels due to classical diseases of the hypothalamic-pituitary-gonadal axis. The benefit:risk ratio is less certain in older men and in those with chronic diseases associated with low testosterone levels. The decision to treat in this setting is much more controversial because there are few large clinical trials that have demonstrated efficacy and no large clinical trials that have determined potential risks of increasing the incidence of clinical prostate cancers or cardiovascular events. We provide a critical review of the evidence that supports treatment and potential risks and ways to reduce the risks if the physician and patient elect testosterone replacement.
Patients with symptoms consistent with testosterone deficiency and low testosterone levels may benefit from testosterone replacement, but risk and monitoring must be considered and appropriate.
Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS ...as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.
Abstract
Context
Studies of the possible cardiovascular risk of testosterone treatment are inconclusive.
Objective
To determine the effect of testosterone treatment on cardiovascular biomarkers in ...older men with low testosterone.
Design
Double-blind, placebo-controlled trial.
Setting
Twelve academic medical centers in the United States.
Participants
In all, 788 men ≥65 years old with an average of two serum testosterone levels <275 ng/dL who were enrolled in The Testosterone Trials.
Intervention
Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months.
Main Outcome Measures
Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage.
Results
Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjusted mean difference, −6.1 mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, −2.0 mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjusted mean difference, −2.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, −1.7 µIU/mL; P = 0.02) and homeostatic model assessment‒insulin resistance (adjusted mean difference, −0.6; P = 0.03). Testosterone did not change triglycerides, d-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo.
Conclusions and Relevance
Testosterone treatment of 1 year in older men with low testosterone was associated with small reductions in cholesterol and insulin but not with other glucose markers, markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.
Compared with placebo, testosterone treatment of older men with low testosterone was associated with small reductions in total, HDL, and LDL cholesterol and in insulin and HOMA-IR but not glucose.
In a randomized trial involving men with hypogonadism and preexisting or a risk of cardiovascular disease, testosterone therapy was noninferior to placebo with respect to major adverse cardiac events.
IMPORTANCE: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. OBJECTIVE: To test the hypothesis that testosterone treatment of older ...men with low testosterone slows progression of noncalcified coronary artery plaque volume. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. INTERVENTION: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). RESULTS: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, −27 Agatston units; 95% CI, −80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. CONCLUSIONS AND RELEVANCE: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
Abstract The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third ...Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.
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