Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men.

Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126 +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.     

The effect of exercise on the production and clearance of testosterone in well trained young men

Tritium-labelled testosterone was infused into four well-trained subjects at rest and during one hour of exercise at about 60% of their maximum aerobic power. This exercise regime led to a mean increase of 27% (range 10-51%) in plasma testosterone concentration. At the same time there were significant decreases in the estimated hepatic plasma flow (EHPF) (45%; range 28-67%), metabolic clearance rate of testosterone (MCRT) (29%; range 18-37%) and plasma volume (8.2%; range 3-10%). The production rate of testosterone decreased by 10% (range 9-22%) but this was not statistically significant. The ratio MCRT:EHPF increased in 3 out of 4 subjects in response to exercise but there was considerable inter-subject variation both at rest and during exercise. These findings suggest that the exercise-induced elevation of testosterone level is due solely to the reduction in the rate at which testosterone is cleared from the plasma. The principal cause of the reduction in MCRT is probably the reduction in EHPF but the variation in the ratio MCRT:EHPF suggests that changes in the extrahepatic clearance of testosterone may also be involved.     

Total and free testosterone in plasma of hypo- and agonadal men.

Plasma total testosterone (T), apparently free T and testosterone binding globulin (TeBG) capacity determined in 14 normal men aged 30-40 years were 461 +/- 100 ng/100 ml, 9.4 +/- 3.0 ng/100 ml and 5.7 +/- 1.9 X 10(-8) M, respectively, whereas in 16 hypogonadal men the corresponding values were 38.6 +/- 27.2 ng/100 ml, 0.47 +/- 0.41 ng/100 ml and 10.4 +/- 3.4 X 10(-8) M showing the TeBG capacity significantly higher (p less than 0.001) in hypogonadal than in normal men. Treatment of 5 hypogonadal subjects with 250 mg testosterone enanthate plus 50 mg testosterone propionate decreased (p less than 0.001) the TeBG level from 14.7 +/- 2.5 X 10(-8YM to 8.3 +/- 1.4 X 10(-8) M on day 8 after a single injection. According to this difference in TeBG, the free T fraction in plasma rose from 0.94% to 1.9% of the total T concentration. These results suggest that alteration of total plasma T affected the TeBG capacity. Decreased T levels raised and increased T concentrations suppressed TeBG, but with a delayed response to the changed T concentrations. The initial mean values in 12 patients with prostatic cancer aged 60-74 years were 397 +/- 165 ng/100 ml, 4.05 +/- 1.8 ng/100 ml and 11.9 +/- 3.3 X 10(-8) M, respectively. The TeBG capacity in these patients was significantly higher and the free T concentration significantly lower (p less than 0.001) than those of the younger normal males. After treatment with 12 g diethylstilbestrol diphosphate and orchidectomy, the TeBG increased to 33.3 +/- 13.1 X 10(-8) M and the plasma free T concentration decreased to the minimal value of 0.053 +/- 0.04 ng/100 ml.     

No effect of short-term testosterone manipulation on exercise substrate metabolism in men.

Compared with women, men use proportionately more carbohydrate and less fat during exercise at the same relative intensity. Estrogen and progesterone have potent effects on substrate use during exercise in women, but the role of testosterone (T) in mediating substrate use is unknown. The purpose of this investigation was to assess how large variations in the concentration of blood T would impact substrate use during exercise in men. Nine healthy, active men were studied in three distinct hormonal conditions: physiological T (no intervention), low T (pharmacological suppression of endogenous T with a gonadotrophin-releasing hormone antagonist), and high T (supplementation with transdermal T). Total carbohydrate oxidation, blood glucose rate of disappearance, and estimated muscle glycogen use were assessed by using stable isotope dilution and indirect calorimetry at rest and while bicycling at approximately 60% of peak O2 consumption for 90 min. Relative to the physiological condition (T = 5.5 +/- 0.5 ng/ml), total plasma T was considerably suppressed in low T (0.8 +/- 0.1) and elevated in high T (10.9 +/- 1.1). Despite the large changes in plasma T, carbohydrate oxidation, glucose rate of disappearance, and estimated muscle glycogen use were very similar across the three conditions. There were also no differences in plasma concentrations of glucose, insulin, lactate, or free fatty acids. Plasma estradiol (E) concentrations were elevated in high T, but correlations between substrate use and plasma concentrations of T, E, or the T-to-E ratio were very weak (r2 < 0.20). In conclusion, unlike the effect of acute elevation in E to constrain carbohydrate use in women, acute changes in circulating T concentrations do not appear to alter substrate use during exercise in men.     

Baby cries and nurturance affect testosterone in men

Testosterone (T) is generally theorized within a trade-off framework that contrasts parenting and low T with competitive challenges and high T. Paradoxically, baby cues increase T, prompting questions of whether T or its behavioral expression has been mischaracterized. We tested 55 men using a novel interactive infant doll paradigm, and results supported our hypotheses: We showed for the first time that baby cries do decrease T in men, but only when coupled with nurturant responses. In contrast, baby cries uncoupled from nurturant responses increased T. These findings highlight the need to partition infant cues and interactions into nurturant versus competitive-related contexts to more accurately conceptualize T, as per the Steroid/Peptide Theory of Social Bonds. This experiment also supports the utility of this paradigm for studying effects of infant interactions on hormonal responses, which may provide critical insights into ameliorating the darker sides of caregiving (e.g. anger, frustration, violence) and enhancing the positive sides (e.g. intimacy, nurturance, reward).     

Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting.

Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). Testosterone and exercise increase muscle mass in men with AWS, with unclear effects on muscle composition. We examined muscle composition in 54 eugonadal men with AWS who were randomized to 1) testosterone (200 mg im weekly) or placebo and simultaneously to 2) resistance training or no training in a 2 x 2 factorial design. At baseline and after 12 wk, we performed assessments of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition. Leaner muscle has greater attenuation. Baseline muscle attenuation correlated inversely with whole body fat mass (r = -0.52, P = 0.0001). This relationship persisted in a model including age, body mass index, testosterone level, viral load, lean body mass, and thigh muscle cross-sectional area (P = 0.02). Testosterone (P = 0.03) and training (P = 0.03) increased muscle attenuation. These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training. Anabolic therapy in these patients increases muscle leanness.     

Diurnal variations of plasma testosterone in men

Plasma testosterone (T) levels were assayed by a Competitive Protein Binding (CPB) technique in a group of 31 healthy males. In 22 subjects a single blood sample was taken between 8:00 and 9:00 A.M. and the mean T concentration was 6.84 ± 2.11 ng/ml. In the other 9 normal men, blood samples were taken every 4 hours. The existence of temporal variations for testosterone was confirmed by finding the highest mean plasma levels at 4:00 A.M. (9.28 ± 1.17 ng/ml) and lowest mean levels at 8:00 P.M. (2.66 ± 0.52 ng/ml).     

Acute suppression of endogenous testosterone levels by exogenous testosterone in normal men

The effect of exogenous testosterone on endogenous plasma testosterone was studied in normal men. Intramuscularly administered testosterone-19,19,19-d3 rapidly appeared in the systemic circulation in large amounts. Endogenous plasma testosterone was suppressed to near-castrate levels. The suppressed level began to rise between 6 and 10 h, and reached a preinjection level at 24 h after the injection. Plasma LH decreased with a concomitant decrease in endogenous testosterone and began to rise as soon as plasma total testosterone returned to physiological levels.     

LH secretion and testosterone concentrations are blunted after resistance exercise in men.

This study examined the hypothesis that exercise-induced changes in circulating testosterone would be centrally mediated via hypothalamic-pituitary release of luteinizing hormone (LH). We tested this hypothesis by examining overnight LH, total and free testosterone (TT and FT), and cortisol (C) concentrations in 10 young healthy men (21 +/- 1 yr) during two experimental sessions: a control and an acute heavy-resistance exercise bout (50 total sets consisting of squats, bench press, leg press, and latissimus dorsi pull-down). Exercise was performed from 1500 to 1700, and blood sampling began at 1700 and continued until 0600 the next morning. Blood was sampled every 10 min for LH and every hour for TT, FT, and C. Hormonal concentrations were determined via RIA, and the secretion characteristics of LH were analyzed with deconvolution analysis. When overnight postexercise concentrations were compared with control concentrations, no statistically significant (P < or = 0.05) differences were observed for LH half-life, LH pulse frequency, interpulse interval, pulse amplitude, or pulse mass. Significant differences were observed for LH production rate (13.6 +/- 4 and 17.9 +/- 5 IU. l distribution volume(-1) x day(-1) for exercise and control, respectively, a 24% reduction). For the ANOVA marginal main effect means due to condition, C was significantly elevated (5.9 +/- 0.7 vs. 4.0 +/- 0.4 microg/dl), while TT (464 +/- 23 vs. 529 +/- 32 ng/dl) and FT (15.6 +/- 0.7 vs. 18.3 +/- 0.9 pg/ml) were significantly decreased for the exercise condition. These data demonstrate that the decline in overnight testosterone concentrations after acute heavy-resistance exercise is accompanied by a blunted LH production rate and elevated C concentrations.     

Serum testosterone concentration and penile tumescence changes in men

Serum testosterone concentration of 24 human males was correlated with penile diameter changes in response to erotic stimuli. Mean testosterone concentration was significantly and negatively correlated with latency to maximum tumescence and it is hoped that this finding will shed light on the psychophysiological mechanisms involved in normal and impaired erectile function.     

Attractive men induce testosterone and cortisol release in women

Recently, Roney et al. (Roney, J.R., Lukaszewski, A.W., Simmons, Z.L., 2007. Rapid endocrine responses of young men to social interactions with young women. Horm. Behav. 52, 326-33; Roney, J.R., Mahler, S.V., Maestripieri, D., 2003. Behavioral and hormonal responses of men to brief interactions with women. Evol. Hum. Behav. 24, 365-375) demonstrated that men release testosterone and cortisol in response to brief social interactions with young women. The current experiment examined whether women show a similar endocrine response to physically and behaviorally attractive men. 120 women (70 naturally-cycling and 50 using hormonal contraceptives) were shown one of four 20-minute video montages extracted from popular films, depicting the following scenarios: 1) an attractive man courting a young woman (experimental stimulus), 2) a nature documentary (video clip control), 3) an unattractive older man courting a woman (male control), and 4) an attractive woman with no men present (female control). Saliva samples were taken before and after presentation of the stimulus, and were later analyzed for testosterone and cortisol content via enzyme immunoassay. Naturally-cycling women experienced a significant increase in both testosterone and cortisol in response to the experimental stimulus but to none of the control stimuli. Participants taking hormonal contraceptives also showed a significant cortisol response to the attractive man. Women may release adrenal steroid hormones to facilitate courtship interactions with high mate-value men.     

Plasma testosterone in prepubertal cryptorchid boys under long-term HCG therapy.

Plasma testosterone concentrations were determined before and after 6 weeks of human chorionic gonadotropin treatment in 36 prepubertal boys with bilateral or unilateral cryptorchidism. Mean +/- SD basal and post-treatment values (ng/100 ml) in the bilateral group were: treatment successful (n = 14): 32 +/- 19 and 302 +/- 49, treatment unsuccessful (n = 12): 20 +/- 15 and 176 +/- 73. The figures for the unilateral group were: treatment successful (n = 6): 23 +/- 9 and 244 +/- 41, treatment unsuccessful (n = 5): 22 +/- 11 and 264 +/- 102. In the bilateral group significant differences in the T response emerged when successfully treated boys were compared to unsuccessfully treated ones. It is concluded that Leydig cell function may be impaired in some cases of cryptorchidism.     

Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men

Muscle mass and strength losses during aging may be associated with declining levels of serum testosterone (T) in men. Few studies have shown a direct relationship between T and muscle mass and strength. Subjects were 262 men, aged 24-90 yr, from the Baltimore Longitudinal Study of Aging, who had T and sex hormone-binding globulin sex hormone-binding globulin (SHBG) measurements, from which the free T index (FTI) was calculated (T/SHBG) from serum samples collected longitudinally since 1963, total body fat mass and arm and leg fat-free mass (FFM) by dual-energy X-ray absorptiometry and arm and leg strength by dynanomometry. Mixed-effects models estimated T and FTI at the time of mass and strength measurements. Age, total body fat, arm and leg FFM, T, and FTI were significantly associated with concentric and eccentric strength. FTI, not T, was modestly, but directly, related to arm and leg strength after fat, arm and leg FFM, height, and age were accounted for and indirectly through body mass. FTI is a better predictor of arm and leg strength than T in aging men.