Poor levels of agreement between serum and saliva testosterone measurement following exercise training in aging men.

Testosterone (T) is a biologically important androgen that demonstrates a widely-known natural decline with advancing age. The use of salivary T (sal-T), as a determinant of systemic T, has shown promising results in recent years. However, the strength of the salivary-serum T relationship may be affected by measurement method and binding capacity with salivary proteins. The potential influence exercise may impact on this relationship is unstudied in aging men. Therefore, the aim of the present investigation was to examine the relationship of the delta change (Δ) in sal-T with Δserum T following six weeks exercise training. Fifteen sedentary (SED) males (aged 60.4 ± 5.0 years of age) and 20 lifelong exercising (LE) males (60.4 ± 4.7 years of age) were participated. Pearson's correlation coefficient revealed sal-T did not correlate with total testosterone (TT), sex hormone binding globulin (SHBG), bioactive T (bio-T), or free T (free-T) at week 0 or week 6. Δsal-T did not correlate with ΔTT, ΔSHBG, Δbio-T or Δfree-T (r = 0.271, p = 0.180; r = 0.197, p = 0.335; r = 0.258, p = 0.205; and r = 0.257, p = 0.205, respectively). In conclusion, poor levels of agreement existed between saliva and serum measurements of T in response to exercise amongst aging men.

Resting steroid hormone concentrations in lifetime exercisers and lifetime sedentary males.

INTRODUCTION: Advancing age in men is associated with a progressive decline in serum testosterone (T) and interactions between exercise, aging and androgen status are poorly understood. The primary aim of this study was to establish the influence of lifelong training history on serum T, cortisol (C) and sex hormone binding globulin (SHBG) in aging men. A secondary aim was to determine the agreement between serum and salivary measurement of steroid hormones in ageing men. METHODS: Serum and salivary steroid hormones (serum C, T and SHBG, and salivary measures of C and T) were determined and compared between two distinct groups; lifelong exercising males (LE [n = 20], 60.4 ± 4.7 year) and age matched lifelong sedentary individuals (SED [n = 28], 62.5 ± 5.3 years). RESULTS: T-test revealed a lack of significant differences for serum C or SHBG between LE and SED, while Mann-Whitney U revealed a lack of differences in total T (TT), bioavailable T (bio-T) or free testosterone (free-T). Further, salivary T (sal-T) did not correlate with serum markers of T in LE, SED, or when pooled (r = 0.040; p > 0.05). CONCLUSIONS: Findings from this investigation suggested that resting levels of serum T and calculated free-T was unable to distinguish between diverse lifelong training histories in aging men. Further, sal-T was not an appropriate indicator of serum T and calculated free-T values in older males and considerable caution should be exercised when interpreting sal-T measurements in aging males.

Exercise-induced oxidative-nitrosative stress is associated with impaired dynamic cerebral autoregulation and blood-brain barrier leakage.

The present study examined whether dynamic cerebral autoregulation and blood-brain barrier function would become compromised as a result of exercise-induced oxidative-nitrosative stress. Eight healthy men were examined at rest and after an incremental bout of semi-recumbent cycling exercise to exhaustion. Changes in a dynamic cerebral autoregulation index were determined during recovery from continuous recordings of blood flow velocity in the middle cerebral artery (MCAv) and mean arterial pressure during transiently induced hypotension. Electron paramagnetic resonance spectroscopy and ozone-based chemiluminescence were employed for direct detection of spin-trapped free radicals and nitric oxide metabolites in venous blood. Neuron-specific enolase, S100ß and 3-nitrotyrosine were determined by ELISA. While exercise did not alter MCAv, it caused a mild reduction in the autoregulation index (from 6.9 ± 0.6 to 5.5 ± 0.9 a.u., P < 0.05) that correlated directly against the exercise-induced increase in the ascorbate radical, 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide and N-tert-butyl-α-phenylnitrone adducts, 3-nitrotyrosine and S100ß (r = -0.66 to -0.76, P < 0.05). In contrast, no changes in neuron-specific enolase were observed. In conclusion, our findings suggest that intense exercise has the potential to increase blood-brain barrier permeability without causing structural brain damage subsequent to a free radical-mediated impairment in dynamic cerebral autoregulation.

Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness?

This study examined whether hypoxia causes free radical-mediated disruption of the blood-brain barrier (BBB) and impaired cerebral oxidative metabolism and whether this has any bearing on neurological symptoms ascribed to acute mountain sickness (AMS). Ten men provided internal jugular vein and radial artery blood samples during normoxia and 9-h passive exposure to hypoxia (12.9% O(2)). Cerebral blood flow was determined by the Kety-Schmidt technique with net exchange calculated by the Fick principle. AMS and headache were determined with clinically validated questionnaires. Electron paramagnetic resonance spectroscopy and ozone-based chemiluminescence were employed for direct detection of spin-trapped free radicals and nitric oxide metabolites. Neuron-specific enolase (NSE), S100beta, and 3-nitrotyrosine (3-NT) were determined by ELISA. Hypoxia increased the arterio-jugular venous concentration difference (a-v(D)) and net cerebral output of lipid-derived alkoxyl-alkyl free radicals and lipid hydroperoxides (P < 0.05 vs. normoxia) that correlated with the increase in AMS/headache scores (r = -0.50 to -0.90, P < 0.05). This was associated with a reduction in a-v(D) and hence net cerebral uptake of plasma nitrite and increased cerebral output of 3-NT (P < 0.05 vs. normoxia) that also correlated against AMS/headache scores (r = 0.74-0.87, P < 0.05). In contrast, hypoxia did not alter the cerebral exchange of S100beta and both global cerebral oxidative metabolism (cerebral metabolic rate of oxygen) and neuronal integrity (NSE) were preserved (P > 0.05 vs. normoxia). These findings indicate that hypoxia stimulates cerebral oxidative-nitrative stress, which has broader implications for other clinical models of human disease characterized by hypoxemia. This may prove a risk factor for AMS by a mechanism that appears independent of impaired BBB function and cerebral oxidative metabolism.

Potential benefits of recombinant human growth hormone (rhGH) to athletes.

Athletes have enjoyed almost a thirty year amnesty of rhGH abuse, which they consider has contributed to the winning of medals and the breaking of world records. Such a reprieve is almost at an end, since WADA have identified a method to detect rhGH abuse. Or have they? The anecdotal word "on the street" is that rhGH is still undetectable and athletes believe that the benefits, at the dosages they administer, far outweigh the risks! Scientists are aware that in a hormone deficiency condition, replacement can halt and in certain situations reverse some of the adverse effects. Growth hormone deficiency can lead to a loss of skeletal muscle mass and an increase in abdomino-visceral obesity, which is reversed on replacement with rhGH. Since the availability of GH, athletes have been trying to extrapolate these effects from the deficiency state to the healthy corpus and increase their sporting prowess. Past confessions from athletes, such as Ben Johnson, Kelly White, Tim Montgomery, Marion Jones and currently Dwain Chambers have demonstrated that they are prepared to tread the very fine lines that separate the "men from the boys". Rewards are so great, that anonymous surveys have identified that athletes will risk ill health, if they believe they can cheat, win and not get caught. The question that still needs to be answered is, "does growth hormone enhance performance"? Recent research suggests that it could. There is also a suspicion that in "cycled" low supraphysiological doses, it is no where near as harmful as WADA claim it to be.

Physical effects of short-term recombinant human growth hormone administration in abstinent steroid dependency.

BACKGROUND/AIMS: Recombinant human growth hormone (rhGH) as opposed to cadaver pituitary GH is misused for physical improvement. Six days' rhGH administration, in abstinent anabolic-androgenic steroid dependents, was compared with controls. METHOD: Male subjects (n = 48) were randomly divided into two groups: (1): control group (C), n = 24, mean +/- SD, age 32 +/- 11 years, height 1.8 +/- 0.06 m; (2): rhGH-using group (0.058 IU.kg(-1).day(-1)) (GH), n = 24, mean +/- SD, age 32 +/- 9 years, height 1.8 +/- 0.07 m. Physiological measurements included anthropometry, strength, power and peak oxygen uptake (VO(2) peak). Biochemical measurements included haemoglobin, packed cell volume, glucose, sodium, potassium, urea, creatinine, total protein, albumin, thyroid function, testosterone, prolactin, cortisol, GH and insulin-like growth factor-I (IGF-I). RESULTS: Strength, peak power output and IGF-I significantly increased and total protein, albumin and free tetra-iodothyronine significantly decreased compared to controls (p < 0.05) and within the GH group (p < 0.017). Fat-free mass index and VO(2) peak significantly increased, while body fat and thyroid-stimulating hormone significantly decreased within the GH group (p < 0.017). CONCLUSIONS: Short-term rhGH increased strength and power. Of therapeutic value is the possibility that muscle bulk and strength could be increased in patients with muscle-wasting conditions.

Short-term recombinant human growth hormone administration improves respiratory function in abstinent anabolic-androgenic steroid users.

OBJECTIVES: To determine whether 6 days recombinant human growth hormone (rhGH) administration, in an abstinent anabolic-androgenic steroid (AAS) using group had any respiratory, endurance exercise and biochemical effects compared with an abstinent AAS control group. METHODS: Male subjects (n=48) were randomly divided, using a single blind procedure into two groups: (1) control group (C) n=24, means+/-SD, age 32+/-11 years; height 1.8+/-0.06 m; (2) rhGH using group (0.019 mg kg(-1) day(-1)) (GH) n=24, means+/-SD, age 32+/-9 years; height 1.8+/-0.07 m. Anthropometry, respiratory muscle function and endurance exercise were investigated. Respiratory measurements examined, were forced expiratory volume in one second, forced vital capacity, maximum inspiratory pressure and maximum expiratory pressure. Endurance exercise was assessed by measuring peak oxygen uptake (VO(2)peak). Biochemical analysis included; haemoglobin, packed cell volume, glucose, sodium, urea, creatinine, total protein, albumin, testosterone and insulin like growth factor-I (IGF-I). RESULTS: Forced expiratory volume in one second/forced vital capacity, maximum inspiratory pressure, maximum expiratory pressure, and IGF-I significantly increased compared with the control group (all P<0.05). Body mass index, fat free mass index, peak oxygen uptake, maximum inspiratory pressure, maximum expiratory pressure, IGF-I and serum sodium significantly increased, whilst body fat, total protein and albumin, significantly decreased within the GH group (all P<0.017). CONCLUSION: The findings of this study indicated that short-term high dose rhGH increased aerobic performance and respiratory muscle strength in former AAS users.

Recombinant human growth hormone in abstinent androgenic-anabolic steroid use: psychological, endocrine and trophic factor effects.

This study examined whether six days recombinant human growth hormone (rhGH) affected psychological profile in an abstinent androgenic-anabolic steroid (AAS) abusing group, compared with an abstinent AAS control group. Male subjects (n = 48) were assigned in a random fashion into one of two groups: (1): (n=24) control group (C); (2): (n=24) rhGH group (GH). A hospital anxiety scale (HADS) questionnaire was completed by all subjects. Physiological responses investigated included anthropometry. Biochemical markers examined included; serum glucose, sodium, urea, lipid profile, high sensitivity C-reactive protein (hsCRP), homocysteine (HCY), tetra-iodothyronine (T4), thyroid stimulating (TSH), luteinising (LH) and follicle stimulating (FSH) hormones, testosterone (T), prolactin (PRL), cortisol and insulin like growth factor-1 (IGF-I). HADS questionnaire significantly decreased in both anxiety (A) and depression (D) symptoms within GH (P<0.017) and compared with C (P<0.05). Body mass index (BMI) and fat-free mass index (FFMI) significantly increased (both P<0.017) while body fat significantly decreased within GH (P<0.017). IGF-I significantly increased within GH (P<0.017) and significantly increased compared with C (P<0.05). Serum sodium significantly increased (P<0.017) and serum HCY, hsCRP, TSH and T4, significantly decreased within GH (all P<0.017). PRL significantly increased and T4 significantly decreased compared with C (both P<0.05). The findings of this study suggest that short term use of rhGH has beneficial effects on mental state in individuals who were previous abusers of AAS and appeared to have a beneficial effect on cardiovascular risk markers associated with adverse mental health.

Evidence for a decrease in cardiovascular risk factors following recombinant growth hormone administration in abstinent anabolic-androgenic steroid users.

OBJECTIVES: To determine whether six days recombinant human growth hormone (rhGH) in an abstinent anabolic-androgenic steroid (AAS) group had any cardiovascular and biochemical effects compared with a control group. METHODS: Male subjects (n=48) were randomly divided, using a single blind procedure into two groups: (1) control group (C) n=24, mean+/-SD, age 32+/-11 years; height 1.8+/-0.06m; (2) rhGH using group (0.058IUkg(-1)day(-1)) (GH) n=24, mean+/-SD, age 32+/-9 years; height 1.8+/-0.07m. Physiological responses, anthropometry, arterial pulse wave velocity (APWV), blood pressure (BP), heart rate (HR), peak oxygen uptake (VO(2) peak) and biochemical indices were investigated. RESULTS: Body mass index, fat-free mass index and VO(2) peak significantly increased while body fat significantly decreased within GH (all P<0.017). Insulin like growth factor-I significantly increased within GH (P<0.017) and compared with C (P<0.05). Serum sodium significantly increased (P<0.017) and serum homocysteine, high sensitivity C-reactive protein, thyroid stimulating hormone and tetra-iodothyronine (T(4)), significantly decreased within GH (all P<0.017). T(4) significantly decreased compared with C (P<0.05). Arterial pulse wave velocity, peak and recovery systolic and diastolic BP, significantly decreased compared with C (P<0.05). Resting HR and rate pressure product (RPP) significantly increased compared with C (P<0.05). CONCLUSION: The findings of this study suggest that short term use of rhGH may have beneficial effects on endothelial function and specific inflammatory markers of cardiovascular disease in abstinent AAS users, but may have an adverse effect on the cardiovascular system, as evidenced by the increase in resting RPP.

Vitamin C prophylaxis promotes oxidative lipid damage during surgical ischemia-reperfusion.

Reactive oxygen species (ROS) have been implicated in the cellular membrane damage and postoperative morbidity associated with obligatory ischemia-reperfusion (I-R) during vascular surgery. Thus, a clinical study was undertaken to evaluate the effects of ascorbate prophylaxis on ROS exchange kinetics in 22 patients scheduled for elective abdominal aortic aneurysm (AAA) or infra-inguinal bypass (IIB) repair. Patients were assigned double-blind to receive intravenous sodium ascorbate (2 g vitamin C, n=10) or placebo (0.9% saline, n=12) administered 2 h prior to surgery. Blood samples were obtained from the arterial and venous circulation proximal to the respective sites of surgical repair (local) and from an antecubital vein (peripheral) during cross-clamping (ischemia) and within 60 s of clamp release (reperfusion). Ascorbate supplementation increased the venoarterial concentration difference (v-adiff) of lipid hydroperoxides (LH), interleukin (IL)-6 and vascular endothelial growth factor (VEGF) protein during ischemia. This increased the peripheral concentration of LH, total creatine phosphokinase (CPK), and VEGF protein during reperfusion (P<0.05 vs placebo). Electron paramagnetic resonance (EPR) spectroscopy confirmed that free iron was available for oxidative catalysis in the local ischemic venous blood of supplemented patients. An increased concentration of the ascorbate radical (A.-) and alpha-phenyl-tert-butylnitrone (PBN) adducts assigned as lipid-derived alkoxyl (LO.) and alkyl (LC.) species were also detected in the peripheral blood of supplemented patients during reperfusion (P<0.05 vs ischemia). In conclusion, these findings suggest that ascorbate prophylaxis may have promoted iron-induced oxidative lipid damage via a Fenton-type reaction initiated during the ischemic phase of surgery. The subsequent release of LH into the systemic circulation may have catalyzed formation of second-generation radicals implicated in the regulation of vascular permeability and angiogenesis.

Manipulation of systemic oxygen flux by acute exercise and normobaric hypoxia: implications for reactive oxygen species generation.

Maximal exercise in normoxia results in oxidative stress due to an increase in free radical production. However, the effect of a single bout of moderate aerobic exercise performed in either relative or absolute normobaric hypoxia on free radical production and lipid peroxidation remains unknown. To examine this, we randomly matched {according to their normobaric normoxic VO2peak [peak VO2 (oxygen uptake)]} and assigned 30 male subjects to a normoxia (n = 10), a hypoxia relative (n = 10) or a hypoxia absolute (n = 10) group. Each group was required to exercise on a cycle ergometer at 55% of VO2peak for 2 h double-blinded to either a normoxic or hypoxic condition [FiO2 (inspired fraction of O2) = 0.21 and 0.16 respectively]. ESR (electron spin resonance) spectroscopy in conjunction with ex vivo spin trapping was utilized for the direct detection of free radical species. The main findings show that moderate intensity exercise increased plasma-volume-corrected free radical and lipid hydroperoxide concentration (pooled rest compared with exercise data, P < 0.05); however, there were no selective differences between groups (statexgroup interaction, P > 0.05). The delta change in free radical concentration was moderately correlated with systemic VO2 (r2 = 0.48, P < 0.05). The hyperfine coupling constants recorded from the ESR spectra [aN = 13.8 Gauss, and a(H)beta = 1.9 Gauss; where 1 Gauss = 10(-4) T (telsa)] are suggestive of oxygen-centred free radical species formed via the decomposition of lipid hydroperoxides. Peripheral leucocyte and neutrophil cells and total CK (creatine kinase) activity all increased following sustained exercise (pooled rest compared with exercise data, P < 0.05), but no selective differences were observed between groups (state x group interaction, P > 0.05). We conclude that a single bout of moderate aerobic exercise increases secondary free radical species. There is also evidence of exercise-induced muscle damage, possibly caused by the increase in free radical generation.

Metabolic implications of resistive force selection for oxidative stress and markers of muscle damage during 30 s of high-intensity exercise.

The purpose of this study was to compare power outputs, and blood concentrations of lipid hydroperoxides (LH), malondialdehyde (MDA), creatine kinase (CK), myoglobin (Mb) and lactate ([La-]B) following 30 s of maximal cycle ergometry when resistive forces were derived from total-body mass (TBM) or fat-free mass (FFM). Alpha-tocopherol (AT), retinol (R) and uric acid (UA) concentrations were also measured to qualify the activity of antioxidants. Cardiac troponin levels were determined to exclude myocardial damage and to verify that any CK was predominantly derived from skeletal muscle. Differences (P<0.05) in peak power output, pedal velocity and resistive forces were observed when the TBM and FFM protocols were compared [953 (114) W vs 1,020 (134) W; 134 (8) rpm vs 141 (7) rpm; 6 (1) kg vs 5 (1) kg respectively). LH and MDA concentrations increased immediately post-exercise during the TBM protocol only (P<0.05) and were greater when compared to FFM (P<0.05). LH and MDA values decreased 24 h post-exercise. Increases in CK concentrations were recorded immediately post-exercise for both the TBM and FFM protocols with greater concentrations recorded for TBM (P<0.05). Decreases were observed 24 h post-exercise. Mb concentrations were greater immediately post-exercise for the TBM protocol and were greater than those recorded for FFM (P<0.05). Values decreased 24 h later (P<0.05). AT and UA concentrations decreased immediately post-exercise for both protocols (P<0.05) and increased 24 h later (P<0.05). There were no changes observed in R concentrations at any of the blood sampling stages. [La-]B increased (P<0.05) immediately post-exercise for both protocols, and decreased 24 h later (P<0.05). The results of the study suggest that greater power outputs are obtainable with significantly less oxidative stress and muscle disruption when resistive forces reflect FFM mass as opposed to TBM.

Symptoms of infection and acute mountain sickness; associated metabolic sequelae and problems in differential diagnosis.

Infections and acute mountain sickness (AMS) are common at high altitude, yet their precise etiologies remain elusive and the potential for differential diagnosis is considerable. The present study was therefore designed to compare clinical nonspecific symptoms associated with these pathologies and basic changes in free radical and amino-acid metabolism. Nineteen males were examined at rest and after maximal exercise at sea level before (SL(1)/SL(2)) and following a 20 +/- 5 day ascent to Kanchenjunga base camp located at 5100 m (HA). Four subjects with symptoms consistent with an ongoing respiratory and recent gastrointestinal infection were also diagnosed with clinical AMS on the evening of day 1 at HA. These and six other subjects recovering from symptoms consistent with a respiratory infection presented with a greater increase (HA minus SL(1)) in AMS scores and resting venous concentration of lipid hydroperoxides (LH) and in total creatine phosphokinase and ratio of free tryptophan/branched chain amino acids, and greater decrease in glutamine (Gln) compared to healthy controls (n = 9, p < 0.05). The decrease in Gln was consistently related to the altitude/exercise-induced increase in LH (r = -0.69/r = -0.45; p < 0.05) and altitude-induced increase in myoglobin (r = -0.73, p < 0.05). These findings highlight the potential for the misdiagnosis of altitude illness due to the similarity of nonspecific constitutional symptoms associated with infection and AMS. Both conditions were characterized by parallel changes in peripheral biomarkers related to free-radical, skeletal muscle damage and amino acid metabolism. While clearly not establishing cause and effect, free radical-mediated changes in peripheral amino acid metabolism known to influence immune and cerebral serotoninergic function may enhance susceptibility to and/or delay recovery from altitude illness.