Testosterone Attenuates Age-Related Fall in Aerobic Function in Mobility Limited Older Men With Low Testosterone

Abstract Context: Testosterone increases skeletal muscle mass and strength, but the effects of testosterone on aerobic performance in mobility-limited older men have not been evaluated. Objective: To determine the effects of testosterone supplementation on aerobic performance, assessed as peak oxygen uptake (V̇O2peak) and gas exchange lactate threshold (V̇O2θ), during symptom-limited incremental cycle ergometer exercise. Design: Subgroup analysis of the Testosterone in Older Men with Mobility Limitations Trial. Setting: Exercise physiology laboratory in an academic medical center. Participants: Sixty-four mobility-limited men 65 years or older with low total (100–350 ng/dL) or free (<50 pg/dL) testosterone. Interventions: Participants were randomized to receive 100-mg testosterone gel or placebo gel daily for 6 months. Main Outcome Measures: V̇O2peak and V̇O2θ from a symptom-limited cycle exercise test. Results: Mean (SD) baseline V̇O2peak was 20.5 (4.3) and 19.9 (4.7) mL/kg/min for testosterone and placebo, respectively. V̇O2peak increased by 0.83 (2.4) mL/kg/min in testosterone but decreased by −0.89 (2.5) mL/kg/min in placebo (P = .035); between group difference in change in V̇O2peak was significant (P = .006). This 6-month reduction in placebo was greater than the expected −0.4-mL/kg/min/y rate of decline in the general population. V̇O2θ did not change significantly in testosterone but decreased by 1.1 (1.8) mL/kg/min in placebo, P = .011 for between-group comparisons. Hemoglobin increased by 1.0 ± 3.5 and 0.1 ± 0.8 g/dL in testosterone and placebo groups, respectively. Conclusion: Testosterone supplementation in mobility-limited older men increased hemoglobin and attenuated the age-related declines in V̇O2peak and V̇O2θ. Long-term intervention studies are needed to determine the durability of this effect.

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Evaluating Age-related Disparity of Outcomes in Ewing Sarcoma Patients Treated at a Pediatric Academic Medical Center

Journal of Pediatric Hematology/Oncology ◽

10.1097/mph.0000000000001891 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Michael P. Perisa ◽

Joseph Stanek ◽

Bhuvana A. Setty ◽

Kathleen Nicol ◽

Nicholas Yeager

Keyword(s):

Ewing Sarcoma ◽

Medical Center ◽

Academic Medical Center ◽

Age Related ◽

Academic Medical

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Age Attenuates Testosterone Secretion Driven by Amplitude-Varying Pulses of Recombinant Human Luteinizing Hormone during Acute Gonadotrope Inhibition in Healthy Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-2704 ◽

2007 ◽

Vol 92 (9) ◽

pp. 3626-3632 ◽

Cited By ~ 24

Author(s):

Paul Y. Takahashi ◽

Patrick Votruba ◽

Mohammed Abu-Rub ◽

Kristi Mielke ◽

Johannes D. Veldhuis

Keyword(s):

Half Life ◽

Medical Center ◽

Academic Medical Center ◽

Community Dwelling ◽

Controlled Study ◽

Deconvolution Analysis ◽

Healthy Men ◽

Age Related ◽

Aging Men ◽

The Impact

Abstract Context: Whether testosterone (Te) depletion in aging men reflects deficits in the testis, hypothalamus, and/or pituitary gland is unknown. Objective: Our objective was to quantify the impact of age on gonadal Te secretion driven by amplitude-varying pulses of recombinant human LH (rhLH) in the absence of confounding by endogenous hypothalamo-pituitary signals. Design: This was a double-blind, placebo-controlled study. Setting: The setting was an academic medical center. Subjects: Fifteen healthy community-dwelling men ages 22–78 yr were included in the study. Intervention: Saline or four separate rhLH doses were each infused twice iv in randomized order as one pulse every 2 h over 20 h to stimulate Te secretion, after LH secretion was suppressed by a GnRH-receptor antagonist, ganirelix. Main Outcome: LH and Te concentrations were determined in blood samples collected every 5 min. Maximal and minimal (as well as mean) Te responses were regressed linearly on age to reflect LH peak and nadir (and average) effects, respectively. Results: The ganirelix/rhLH paradigm yielded serum LH concentrations of 4.6 ± 0.22 IU/liter (normal range 1–9). By regression analysis, age was associated with declines in rhLH pulse-stimulated peak and nadir (and mean) concentrations of total Te (P = 0.0068), bioavailable Te (P = 0.0096), and free Te (P = 0.013), as well as lower Te/LH concentration ratios (P < 0.005). Deconvolution analysis suggested that the half-life of infused LH increases by 12%/decade (P = 0.044; R2 = 0.28). Conclusions: Infusion of amplitude-varying pulses of rhLH during gonadal-axis suppression in healthy men unmasks prominent age-related deficits in stimulated total (39%), bioavailable (66%), and free (63%) Te concentrations, and a smaller age-associated increase in LH half-life. These data suggest that age-associated factors reduce the efficacy of LH pulses.

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Ten days of exercise training reduces glucose production and utilization during moderate-intensity exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.266.1.e136 ◽

1994 ◽

Vol 266 (1) ◽

pp. E136-E143 ◽

Cited By ~ 18

Author(s):

L. A. Mendenhall ◽

S. C. Swanson ◽

D. L. Habash ◽

A. R. Coggan

Keyword(s):

Endurance Training ◽

Time Course ◽

Plasma Concentrations ◽

Glucose Production ◽

Peak Oxygen Uptake ◽

Cycle Ergometer ◽

Moderate Intensity ◽

Moderate Intensity Exercise ◽

Ergometer Exercise ◽

Exercise Induced

We have previously shown that 12 wk of endurance training reduces the rate of glucose appearance (Ra) during submaximal exercise (Coggan, A. R., W. M. Kohrt, R. J. Spina, D. M. Bier, and J. O. Holloszy. J. Appl. Physiol. 68: 990-996, 1990). The purpose of the present study was to examine the time course of and relationship between training-induced alterations in glucose kinetics and endocrine responses during prolonged exercise. Accordingly, seven men were studied during 2 h of cycle ergometer exercise at approximately 60% of pretraining peak oxygen uptake on three occasions: before, after 10 days, and after 12 wk of endurance training. Ra was determined using a primed, continuous infusion of [6,6-2H]glucose. Ten days of training reduced mean Ra during exercise from 36.9 +/- 3.3 (SE) to 28.5 +/- 3.4 mumol.min-1.kg-1 (P < 0.001). Exercise-induced changes in insulin, C-peptide, glucagon, norepinephrine, and epinephrine were also significantly blunted. After 12 wk of training, Ra during exercise was further reduced to 21.5 +/- 3.1 mumol.min-1.kg-1 (P < 0.001 vs. 10 days), but hormone concentrations were not significantly different from 10-day values. The lower glucose Ra during exercise after short-term (10 days) training is accompanied by, and may be due to, altered plasma concentrations of the major glucoregulatory hormones. However, other adaptations must be responsible for the further reduction in Ra with more prolonged training.

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Persistence of supercompensated muscle glycogen in trained subjects after carbohydrate loading

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.1.342 ◽

1997 ◽

Vol 82 (1) ◽

pp. 342-347 ◽

Cited By ~ 18

Author(s):

Harold W. Goforth ◽

Jr., David A. Arnall ◽

Brad L. Bennett ◽

Patricia G. Law

Keyword(s):

Muscle Glycogen ◽

Vastus Lateralis ◽

Endurance Performance ◽

Peak Oxygen Uptake ◽

Cycle Ergometer ◽

Male Athletes ◽

Trained Subjects ◽

Carbohydrate Loading ◽

Low Protein ◽

Ergometer Exercise

Goforth, Jr., Harold W., David A. Arnall, Brad L. Bennett, and Patricia G. Law. Persistence of supercompensated muscle glycogen in trained subjects after carbohydrate loading. J. Appl. Physiol. 82(1): 342–347, 1997.—Several carbohydrate (CHO)-loading protocols have been used to achieve muscle glycogen supercompensation and prolong endurance performance. This study assessed the persistence of muscle glycogen supercompensation over the 3 days after the supercompensation protocol. Trained male athletes completed a 6-day CHO-loading protocol that included cycle ergometer exercise and dietary manipulations. The 3-day depletion phase began with 115 min of cycling at 75% peak oxygen uptake followed by 3 × 60-s sprints and included the subjects consuming a low-CHO/high-protein/high-fat (10:41:49%) diet. Subjects cycled 40 min at the same intensity for the next 2 days. During the 3-day repletion phase, subjects rested and consumed a high-CHO/low-protein/low-fat (85:08:07%) diet, including a glucose-polymer beverage. A 3-day postloading phase followed, which involved a moderately high CHO diet (60%) and no exercise. Glycogen values for vastus lateralis biopsies at baseline and postloading days 1–3 were 408 ± 168 (SD), 729 ± 222, 648 ± 186, and 714 ± 196 mmol/kg dry wt, respectively. The CHO-loading protocol increased muscle glycogen by 1.79 times baseline, and muscle glycogen remained near this level during the 3-day postloading period. Results indicate that supercompensated muscle glycogen levels can be maintained for at least 3 days in a resting athlete when a moderate-CHO diet is consumed.

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Twelve weeks of endurance training increases FFA mobilization and reesterification in postmenopausal women

Journal of Applied Physiology ◽

10.1152/japplphysiol.00116.2010 ◽

2010 ◽

Vol 109 (6) ◽

pp. 1573-1581 ◽

Cited By ~ 14

Author(s):

M. L. Johnson ◽

Z. Zarins ◽

J. A. Fattor ◽

M. A. Horning ◽

L. Messonnier ◽

...

Keyword(s):

Exercise Training ◽

Endurance Training ◽

Plasma Free Fatty Acid ◽

Cycle Ergometer ◽

Peak Oxygen Consumption ◽

Age Related ◽

Ergometer Exercise ◽

Body Weights ◽

Plasma Ffa ◽

Power Outputs

We examined the effects of exercise intensity and training on rates of lipolysis, plasma free fatty acid (FFA) appearance (Ra), disappearance (Rd), reesterification (Rs), and oxidation (RoxP) in postmenopausal (PM) women. Ten sedentary but healthy women (55 ± 0.6 yr) completed 12 wk of supervised endurance exercise training on a cycle ergometer [5 days/wk, 1 h/day, 65% peak oxygen consumption (V̇o2peak)]. Flux rates were determined by continuous infusion of [1-13C]palmitate and [1,1,2,3,3-2H5]glycerol during 90 min of rest and 60 min of cycle ergometer exercise during one pretraining exercise trial [65% V̇o2peak (PRE)] and two posttraining exercise trials [at power outputs that elicited 65% pretraining V̇o2peak (absolute training; ABT) and 65% posttraining V̇o2peak (relative training; RLT)]. Initial body weights (68.2 ± 4.5 kg) were maintained over the course of study. Training increased V̇o2peak by 16.3 ± 3.9% ( P < 0.05) (Zarins ZA, Wallis GA, Faghihnia N, Johnson ML, Fattor JA, Horning MA and Brooks GA. Metabolism 58: 9: 1338–1346, 2009). Glycerol Ra and Rd were elevated in the RLT trial ( P < 0.05), but not the ABT trial after training. Rates of plasma FFA Ra, Rd, and RoxP were elevated during the ABT compared with PRE trial ( P < 0.05). FFA Rs accounted for most (50–70%) of Rd during exercise; training reduced FFA Rs during ABT, but not RLT compared with PRE. We conclude that, despite the large age-related decrease in metabolic scope in PM women, endurance training increases the capacities for FFA mobilization and oxidation during exercises of a given power output. However, after menopause, total lipid oxidation capacity remains low, with reesterification accounting for most of FFA Rd.

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Aromatase and 5α-Reductase Inhibition during an Exogenous Testosterone Clamp Unveils Selective Sex Steroid Modulation of Somatostatin and Growth Hormone Secretagogue Actions in Healthy Older Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-2108 ◽

2009 ◽

Vol 94 (3) ◽

pp. 973-981 ◽

Cited By ~ 27

Author(s):

Johannes D. Veldhuis ◽

Kristi L. Mielke ◽

Mihaela Cosma ◽

Cacia Soares-Welch ◽

Remberto Paulo ◽

...

Keyword(s):

Visceral Fat ◽

Medical Center ◽

Academic Medical Center ◽

Older Men ◽

Sex Steroid ◽

Forward Selection ◽

Growth Hormone Secretagogue ◽

Gh Secretion ◽

Academic Medical ◽

Abdominal Visceral Fat

Abstract Background: How endogenous testosterone (Te), 5α-dihydrotestosterone (DHT), and estradiol (E2) regulate pulsatile GH secretion is not understood. Hypothesis: Conversion of Te to androgenic (Te→DHT) or estrogenic (Te→E2) products directs GH secretion. Subjects and Location: Healthy older men (N = 42, ages 50–79 yr) participated at an academic medical center. Methods: We inhibited 5α-reduction with dutasteride and aromatization with anastrozole during a pharmacological Te clamp and infused somatostatin (SS), GHRH, GH-releasing peptide-2 (GHRP-2), and l-arginine/GHRH/GHRP-2 (triple stimulus) to modulate GH secretion. Endpoints: Deconvolution-estimated basal and pulsatile GH secretion was assessed. Results: Administration of Te/placebo elevated Te by 2.8-fold, DHT by 2.6-fold, and E2 concentrations by 1.9-fold above placebo/placebo. Te/dutasteride and Te/anastrozole reduced stimulated DHT and E2 by 89 and 86%, respectively. Stepwise forward-selection regression analysis revealed that 1) Te positively determines mean (P = 0.017) and peak (P < 0.001) GH concentrations, basal GH secretion (P = 0.015), and pulsatile GH secretion stimulated by GHRP-2 (P < 0.001); 2) Te and E2 jointly predict GH responses to the triple stimulus (positively for Te, P = 0.006, and negatively for E2, P = 0.031); and 3) DHT correlates positively with pulsatile GH secretion during SS infusion (P = 0.011). These effects persisted when abdominal visceral fat was included in the regression. Conclusion: The present outcomes suggest a tetrapartite model of GH regulation in men, in which systemic concentrations of Te, DHT, and E2 along with abdominal visceral fat determine the selective actions of GH secretagogues and SS.

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Effects of postexercise carbohydrate-protein feedings on muscle glycogen restoration

Journal of Applied Physiology ◽

10.1152/jappl.2000.88.6.1976 ◽

2000 ◽

Vol 88 (6) ◽

pp. 1976-1982 ◽

Cited By ~ 44

Author(s):

John A. Carrithers ◽

David L. Williamson ◽

Philip M. Gallagher ◽

Michael P. Godard ◽

Kimberley E. Schulze ◽

...

Keyword(s):

Muscle Glycogen ◽

Exercise Bout ◽

Peak Oxygen Uptake ◽

Cycle Ergometer ◽

Serum Glucose ◽

Cycle Exercise ◽

Blood Samples ◽

Ergometer Exercise ◽

Insulin Responses ◽

Muscle Biopsies

The purpose of this investigation was to determine the effects of postexercise eucaloric carbohydrate-protein feedings on muscle glycogen restoration after an exhaustive cycle ergometer exercise bout. Seven male collegiate cyclists [age = 25.6 ± 1.3 yr, height = 180.9 ± 3.2 cm, wt = 75.4 ± 4.0 kg, peak oxygen uptake (V˙o 2 peak) = 4.20 ± 0.2 l/min] performed three trials, each separated by 1 wk: 1) 100% α-d-glucose [carbohydrate (CHO)], 2) 70% carbohydrate-20% protein (PRO)-10% fat, and 3) 86% carbohydrate-14% amino acid (AA). All feedings were eucaloric, based on 1.0 g ⋅ kg body wt− 1 ⋅ h− 1of CHO, and administered every 30 min during a 4-h muscle glycogen restoration period in an 18% wt/vol solution. Muscle biopsies were obtained immediately and 4 h after exercise. Blood samples were drawn immediately after the exercise bout and every 0.5 h for 4 h during the restoration period. Increases in muscle glycogen concentrations for the three feedings (CHO, CHO-PRO, CHO-AA) were 118 mmol/kg dry wt; however, no differences among the feedings were apparent. The serum glucose and insulin responses did not differ throughout the restoration period among the three feedings. These results suggest that muscle glycogen restoration does not appear to be enhanced with the addition of proteins or amino acids to an eucaloric CHO feeding after exhaustive cycle exercise.

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Contribution of hyperoxia to reduced pulmonary function after deep saturation dives

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.2.657 ◽

1993 ◽

Vol 75 (2) ◽

pp. 657-662 ◽

Cited By ~ 22

Author(s):

E. Thorsen ◽

K. Segadal ◽

J. W. Reed ◽

C. Elliott ◽

A. Gulsvik ◽

...

Keyword(s):

Pulmonary Function ◽

Vital Capacity ◽

Oxygen Toxicity ◽

Hemoglobin Concentration ◽

Peak Oxygen Uptake ◽

Cycle Ergometer ◽

Alveolar Volume ◽

Ergometer Exercise ◽

Before And After ◽

Concentration Changes

Pulmonary function was measured before and after a 28-day saturation dive to a pressure of 0.25 MPa in eight subjects. PO2 was 40 kPa, with periods of 75 kPa for 2 h every 2nd day during the first 14 days, 50 kPa for the next 12 days, and a gradual fall to 21 kPa over the last 2 days in decompression. A 28-day saturation dive with six subjects to a pressure of 0.15 MPa and a PO2 of 21 kPa was used as control. The measurements included static and dynamic lung volumes and flows, transfer factor for carbon monoxide (TLCO), and a cycle ergometer exercise test. There was a significant reduction in TLCO of 9.8 +/- 6.0% (P < 0.001) after the dive when values were corrected for hemoglobin concentration changes. Effective alveolar volume was unchanged. There was a reduction in forced midexpiratory flow rate of 9.8 +/- 7.0% (P < 0.01), but forced vital capacity and forced expired volume in 1 s were unchanged. Peak oxygen uptake was reduced by 10.1 +/- 5.3% (P < 0.001). There were no significant changes in any of the lung function variables after the control dive. Exposure to raised PO2 contributes significantly to the changes in pulmonary function that have been reported after deep saturation dives to pressures of 3.1–4.6 MPa with a similar profile of oxygen exposure. TLCO is apparently a more sensitive index than vital capacity for oxygen toxicity.

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Mechanism of the exercise hyperkalemia: an alternate hypothesis

Journal of Applied Physiology ◽

10.1152/jappl.1997.83.2.631 ◽

1997 ◽

Vol 83 (2) ◽

pp. 631-643 ◽

Cited By ~ 26

Author(s):

Karlman Wasserman ◽

William W. Stringer ◽

Richard Casaburi ◽

Yong-Yu Zhang

Keyword(s):

Oxygen Uptake ◽

Femoral Vein ◽

Early Period ◽

Peak Oxygen Uptake ◽

Cycle Ergometer ◽

Exercise Tests ◽

Early Exercise ◽

Major Mechanism ◽

Alternate Hypothesis ◽

Ergometer Exercise

Wasserman, Karlman, William W. Stringer, Richard Casaburi, and Yong-Yu Zhang. Mechanism of the exercise hyperkalemia: an alternate hypothesis. J. Appl. Physiol. 83(2): 631–643, 1997.—A progressive hyperkalemia is observed as exercise intensity increases. The current most popular hypothesis for the hyperkalemia is that the Na+-K+pump cannot keep pace with the K+efflux from muscle during the depolarization-repolarization process of the sarcolemmal membrane during muscle contraction. In this report, we present data that suggest an alternate hypothesis to those previously described. Because phosphocreatine (PCr) is a highly dissociated acid and creatine is neutral at cell pH, the concentration of nondiffusible anions decreases, and an alkaline reaction takes place when PCr hydrolyzes. This creates a state of cation (K+) excess and H+ depletion in the cell. To examine the balance of K+ and H+ for exercising muscle during the early period of exercise when PCr changes most rapidly, catheters were inserted into the brachial artery and femoral vein (FV) in five healthy subjects who performed two 6-min cycle ergometer exercise tests at 40 and 85% of peak oxygen uptake. FV blood was sampled every 5 s during the first 2 min, then every 30 s for the remaining 4 min of exercise and the first 3 min of recovery, and then less frequently for the next 12 min. Arterial sampling was every 30 s during exercise and simultaneous with FV sampling during recovery. Arterial K+ concentration ([K+]) increase lagged FV [K+] increase. The hyperkalemia observed during early exercise results from K+ release from skeletal muscle. FV [K+] increased by 5 s of the start of exercise and followed the rate of H+ loss from the FV blood for the first 30 s of exercise. FV lactate and Na+ kinetics differed from K+ kinetics during exercise and recovery. As predicted from the PCr hydrolysis reaction, the exercising limb took up H+ and released K+ at the start of exercise (first 30 s) at both exercise intensities, resulting in a FV metabolic alkalosis. K+ release was essentially complete by 3 min, the time at which oxygen uptake (and, presumably, PCr) reached its asymptote. These findings lead us to hypothesize that the early K+release by the cell takes place with H+ exchange and that the major mechanism for the exercise hyperkalemia is the reduction in nondiffusible intracellular anions in the myocyte as PCr hydrolyzes.

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