Distinguishing Increased Adiposity and/or Aerobic Deconditioning as Moderators of Low VO2peak in Obese Men

Peak oxygen uptake (V̇O2peak) in a cardiopulmonary exercise test (CPET) is a strong predictor of morbidity, mortality, and quality of life. V̇O2peak in obese individuals is typically below the lower limit of normal (2 transport and utilization, i.e. aerobic deconditioning; or both. We hypothesized a modified CPET, to measure the fraction of maximum isokinetic power that can be supported by aerobic metabolism, will distinguish between adiposity and deconditioning effects on V̇O2peak. PURPOSE: To compare V̇O2peak and isokinetic neuromuscular performance in obese vs non-obese men. METHODS: A modified CPET with maximal (3 s) isokinetic cycling power at baseline and the limit of ramp-incremental (RI) exercise was used to calculate: A) baseline maximum isokinetic power (Piso); B) tolerance index (TI), % of Piso at V̇O2peak; C) fatigue index (FI), % reduction in Piso per RI-watt at V̇O2peak; D) power reserve (PR), isokinetic power available at V̇O2peak expressed as % RI-wattpeak. The FRIEND nomogram was used to predict V̇O2peak. Data are mean(SD) and were assessed by t-test. RESULTS: Compared to controls (n=24), obese men (n=20) were older (32(5) vs 26(7) yr), had greater BMI (38(6) vs 23(2) kg/m2), but were not different in stature (177(5) vs 180(7) cm) or predicted V̇O2peak (3.49(0.49) vs 3.58(0.36) L/min). Obese men had lower V̇O2peak (2.84(0.42) vs 3.71(0.45) L/min, p2peak (82(15) vs 104(12) %, pIndependent of body mass, obese men had preserved leg strength (normal Piso), but the fraction of maximum isokinetic power supported by aerobic metabolism at RI intolerance was reduced (low TI) with greater fatigability (high FI); each consistent with aerobic deconditioning. A modified CPET with maximal isokinetic power measurements can distinguish the effects of increased adiposity from aerobic deconditioning on V̇O2peak in obese men

Testosterone Administration Decreases Generosity in the Ultimatum Game

How do human beings decide when to be selfish or selfless? In this study, we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design. We also confirmed participants' testosterone levels before and after treatment through blood draws. Using the Ultimatum Game from behavioral economics, we find that men with artificially raised T, compared to themselves on placebo, were 27% less generous towards strangers with money they controlled (95% CI placebo: (1.70, 2.72); 95% CI T: (.98, 2.30)). This effect scales with a man's level of total-, free-, and dihydro-testosterone (DHT). Men in the lowest decile of DHT were 560% more generous than men in the highest decile of DHT. We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them. Our results continue to hold after controlling for altruism. We conclude that elevated testosterone causes men to behave antisocially

Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone.

ObjectiveRecent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial.MethodsThe Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable.ResultsOf 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20).ConclusionAmong older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression

Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests

Semen analysis is the first step to identify male factor infertility. Standardized methods of semen analysis are available allowing accurate assessment of sperm quality and comparison among laboratories. Population-based reference ranges are available for standard semen and sperm parameters. Sperm numbers and morphology are associated with time to natural pregnancy, whereas sperm motility may be less predictive. Routine semen analysis does not measure the fertilizing potential of spermatozoa and the complex changes that occur in the female reproductive tract before fertilization. Whether assisted reproduction technology (ART) is required depends not only on male factors but female fecundity. Newer tests should predict the success of fertilization in vitro and the outcome of the progeny

Testosterone Replacement Therapy in Hypogonadal Men

All approved testosterone replacement methods, when used according to recommendations, can restore normal serum testosterone concentrations, and relieve symptoms in most hypogonadal men. Selection of the method depends on the patient's preference with advice from the physician. Dose adjustment is possible with most delivery methods but may not be necessary in all hypogonadal men. The use of hepatotoxic androgens must be avoided. Testosterone treatment induces reversible suppression of spermatogenesis; if fertility is desired in the near future, human chronic gonadotropin, selective estrogen receptor modulator, estrogen antagonist, or an aromatase inhibitor that stimulates endogenous testosterone production may be used

A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men.

BackgroundA novel formulation of oral testosterone undecanoate (TU) was studied in a long- and short-term phase III trial to evaluate safety and efficacy.MethodsHypogonadal men (age 18-65 years; two morning serum testosterone (T) <300 ng/dl with signs/symptoms) were recruited into a 365 day (trial I) or 105 day (trial II), randomized, multicenter trial. Patients were randomized 1:1 to oral TU (n = 161) or T-gel (n = 160) in trial I, and 3:1 to oral TU, twice daily (BID) JATENZO® (n = 166) or a topical T product [Axiron® (n = 56)] in trial II. Dose adjustments were based on average T concentrations (Cavg). Efficacy was assessed based on T levels, body composition and bone density. Safety was assessed by standard clinical measures.ResultsOral TU efficacy (% of patients with eugonadal T Cavg) was 84% (serum Cavg = 628 ± 343 ng/dl) and 87% (serum T equivalent Cavg ≈ 489 ± 155 ng/dl) in trials I and II, respectively. Oral TU significantly (p <0.0001) improved all Psychosexual Daily Questionnaire parameters in trials I and II. In trial I, lean mass increased 3.2 ± 2.7 kg and fat decreased by 2.4 ± 3.6 kg (both p <0.0001) and bone density improved in hip (+0.012 ± 0.0225 g/cm2) and spine (+0.018 ± 0.0422 g/cm2) after 365 days (both p <0.0001). Oral TU-associated adverse effects were consistent with other T-replacement therapies but oral TU patients experienced a greater number of mild gastrointestinal adverse effects. Oral TU subjects in both studies exhibited an increase in mean systolic blood pressure of about 3-5 mmHg. Oral TU was not associated with liver toxicity nor did it cause an elevation in high-sensitivity C-reactive protein or lipoprotein-associated phospholipase A2 (cardiovascular safety biomarkers) after 365 days of therapy.ConclusionA new oral TU formulation was safe and effective and represents a significant therapeutic advance for the treatment of appropriate hypogonadal men

A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men.

BackgroundA novel formulation of oral testosterone undecanoate (TU) was studied in a long- and short-term phase III trial to evaluate safety and efficacy.MethodsHypogonadal men (age 18-65 years; two morning serum testosterone (T) <300 ng/dl with signs/symptoms) were recruited into a 365 day (trial I) or 105 day (trial II), randomized, multicenter trial. Patients were randomized 1:1 to oral TU (n = 161) or T-gel (n = 160) in trial I, and 3:1 to oral TU, twice daily (BID) JATENZO® (n = 166) or a topical T product [Axiron® (n = 56)] in trial II. Dose adjustments were based on average T concentrations (Cavg). Efficacy was assessed based on T levels, body composition and bone density. Safety was assessed by standard clinical measures.ResultsOral TU efficacy (% of patients with eugonadal T Cavg) was 84% (serum Cavg = 628 ± 343 ng/dl) and 87% (serum T equivalent Cavg ≈ 489 ± 155 ng/dl) in trials I and II, respectively. Oral TU significantly (p <0.0001) improved all Psychosexual Daily Questionnaire parameters in trials I and II. In trial I, lean mass increased 3.2 ± 2.7 kg and fat decreased by 2.4 ± 3.6 kg (both p <0.0001) and bone density improved in hip (+0.012 ± 0.0225 g/cm2) and spine (+0.018 ± 0.0422 g/cm2) after 365 days (both p <0.0001). Oral TU-associated adverse effects were consistent with other T-replacement therapies but oral TU patients experienced a greater number of mild gastrointestinal adverse effects. Oral TU subjects in both studies exhibited an increase in mean systolic blood pressure of about 3-5 mmHg. Oral TU was not associated with liver toxicity nor did it cause an elevation in high-sensitivity C-reactive protein or lipoprotein-associated phospholipase A2 (cardiovascular safety biomarkers) after 365 days of therapy.ConclusionA new oral TU formulation was safe and effective and represents a significant therapeutic advance for the treatment of appropriate hypogonadal men

A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men

Background: A novel formulation of oral testosterone undecanoate (TU) was studied in a long- and short-term phase III trial to evaluate safety and efficacy. Methods: Hypogonadal men (age 18–65 years; two morning serum testosterone (T) <300 ng/dl with signs/symptoms) were recruited into a 365 day (trial I) or 105 day (trial II), randomized, multicenter trial. Patients were randomized 1:1 to oral TU ( n  = 161) or T-gel ( n  = 160) in trial I, and 3:1 to oral TU, twice daily (BID) JATENZO® ( n  = 166) or a topical T product [Axiron® ( n  = 56)] in trial II. Dose adjustments were based on average T concentrations ( C avg). Efficacy was assessed based on T levels, body composition and bone density. Safety was assessed by standard clinical measures. Results: Oral TU efficacy (% of patients with eugonadal T C avg) was 84% (serum C avg = 628 ± 343 ng/dl) and 87% (serum T equivalent C avg ≈ 489 ± 155 ng/dl) in trials I and II, respectively. Oral TU significantly ( p  <0.0001) improved all Psychosexual Daily Questionnaire parameters in trials I and II. In trial I, lean mass increased 3.2 ± 2.7 kg and fat decreased by 2.4 ± 3.6 kg (both p  <0.0001) and bone density improved in hip (+0.012 ± 0.0225 g/cm 2 ) and spine (+0.018 ± 0.0422 g/cm 2 ) after 365 days (both p  <0.0001). Oral TU-associated adverse effects were consistent with other T-replacement therapies but oral TU patients experienced a greater number of mild gastrointestinal adverse effects. Oral TU subjects in both studies exhibited an increase in mean systolic blood pressure of about 3–5 mmHg. Oral TU was not associated with liver toxicity nor did it cause an elevation in high-sensitivity C-reactive protein or lipoprotein-associated phospholipase A 2 (cardiovascular safety biomarkers) after 365 days of therapy. Conclusion: A new oral TU formulation was safe and effective and represents a significant therapeutic advance for the treatment of appropriate hypogonadal men