https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)62167-9.pdf

Frailty in elderly people

To validate the FRAIL scale. Longitudinal study. Community. Representative sample of African Americans age 49 to 65 years at onset of study. The 5-item FRAIL scale (Fatigue, Resistance, Ambulation, Illnesses, & Loss of Weight), at baseline and activities of daily living (ADLs), instrumental activities of daily living (IADLs), mortality, short physical performance battery (SPPB), gait speed, one-leg stand, grip strength and injurious falls at baseline and 9 years. Blood tests for CRP, SIL6R, STNFR1, STNFR2 and 25 (OH) vitamin D at baseline. Cross-sectionally the FRAIL scale correlated significantly with IADL difficulties, SPPB, grip strength and one-leg stand among participants with no baseline ADL difficulties (N=703) and those outcomes plus gait speed in those with no baseline ADL dependencies (N=883). TNFR1 was increased in pre-frail and frail subjects and CRP in some subgroups. Longitudinally (N=423 with no baseline ADL difficulties or N=528 with no baseline ADL dependencies), and adjusted for the baseline value for each outcome, being pre-frail at baseline significantly predicted future ADL difficulties, worse one-leg stand scores, and mortality in both groups, plus IADL difficulties in the dependence-excluded group. Being frail at baseline significantly predicted future ADL difficulties, IADL difficulties, and mortality in both groups, plus worse SPPB in the dependence-excluded group. This study has validated the FRAIL scale in a late middle-aged African American population. This simple 5-question scale is an excellent screening test for clinicians to identify frail persons at risk of developing disability as well as decline in health functioning and mortality.

/pdf/a-simple-frailty-questionnaire-frail-predicts-outcomes-in-1gbcifonbw.pdf

A simple frailty questionnaire (frail) predicts outcomes in middle aged african americans

https://uroweb.org/wp-content/uploads/14-Male-Sexual-Dysfunction_LR1.pdf

Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation.

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.

Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline

percentages with events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, −1.4% to 13.1%). In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41). CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.

https://jamanetwork.com/journals/jama/articlepdf/1764051/joi130078.pdf

Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels

Background Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. Methods Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. Results A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. Conclusions In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy. (ClinicalTrials.gov number, NCT00240981.)

https://www.hormonebalance.org/images/documents/Basari%2010%20TRT%20men%20Cardiac%20events%20NEJM.pdf

Adverse Events Associated with Testosterone Administration

MOBILITY limitation, a common geriatric condition, affects an individual’s quality of life, health care costs, and resource utilization while being predictive of disability, risk of hospitalization, and mortality (1–5). Among the function promoting therapies that are being developed for the treatment of functional limitations, androgens are the farthest in development. Testosterone levels are associated with skeletal muscle mass, lower extremity strength, and physical function (6–12). Men with low free testosterone are at increased risk of mobility limitation and its progression (8). Testosterone supplementation increases skeletal muscle mass (13–21), but its effects on muscle strength and physical function have been inconsistent across trials (13–21). Most testosterone trials have been conducted in healthy older men without functional limitations; the safety and efficacy of testosterone in improving muscle performance and physical function have not been demonstrated in older individuals with mobility limitation.

The Testosterone in Older Men with Mobility Limitations (TOM) Trial was a placebo-controlled randomized trial (22,23), whose aim was to determine whether testosterone therapy in older men with mobility limitation and low total or free testosterone levels improves lower extremity muscle strength and physical function (22). As reported recently (23), because of a significantly higher incidence of adverse cardiovascular events in men assigned to the testosterone arm, the trial’s Data and Safety Monitoring Board recommended that further enrollment and administration of study medications to participants be discontinued.

Here, we evaluated the clinical meaningfulness of the effects of intervention on performance-based as well as self-reported measures of muscle performance and physical function in relation to participant’s perception of change. To determine whether changes in the measures of muscle performance, skeletal muscle mass, and physical function were patient important and thus clinically meaningful, we categorized the participants as “improved” or “not improved” based on whether the change in outcome exceeded the minimally important difference (MID), determined using an anchor-based method within this trial. We analyzed the factors associated with improvements in outcomes and explored the relation between change in efficacy outcomes and adverse events.

Clinical Meaningfulness of the Changes in Muscle Performance and Physical Function Associated With Testosterone Administration in Older Men With Mobility Limitation

Context Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterone's effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood. Objective To determine whether testosterone's effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2). Design, Setting, and Patients The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010. Interventions Eight treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups). Main Outcome Measures The primary outcome was change in fat-free mass; secondary outcomes: changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels. Results A total of 139 men were randomized; 102 completed the 20-week intervention. Men assigned to dutasteride were similar at baseline to those assigned to placebo. The mean fat-free mass gained by the dutasteride groups was 0.6 kg (95% CI, −0.1 to 1.2 kg) when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg) for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI, 6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups was 0.8 kg (95% CI, −0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to 6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels did not differ between groups. Conclusion Changes in fat-free mass in response to graded testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo, indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle. Trial Registration clinicaltrials.gov Identifier: NCT00493987

https://jamanetwork.com/journals/jama/articlepdf/1105045/joc25010_931_939.pdf

Effect of Testosterone Supplementation With and Without a Dual 5α-Reductase Inhibitor on Fat-Free Mass in Men With Suppressed Testosterone Production: A Randomized Controlled Trial

Geeta Bhasin

Papers

Adverse Events Associated with Testosterone Administration

Clinical Meaningfulness of the Changes in Muscle Performance and Physical Function Associated With Testosterone Administration in Older Men With Mobility Limitation

Effect of Testosterone Supplementation With and Without a Dual 5α-Reductase Inhibitor on Fat-Free Mass in Men With Suppressed Testosterone Production: A Randomized Controlled Trial