Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men

The aging male: investigation, treatment and monitoring of late-onset hypogonadism in males

Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. The demographics clearly demonstrate the increasing percentage of the population that is in the older age groups. The data also support the concept that testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adults (age 20-30 years) men. The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment on multiple target organs of hypogonadal men and recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. Long-term data on the effects of testosterone treatment in the older population are limited and specific risk data on the prostate and cardiovascular systems are needed. Answers to key questions of functional benefits that may retard frailty of the elderly are not yet available. The recommendations described below were prepared for the International Society of Andrology (ISA) and the International Society for the Study of the Aging Male (ISSAM) following a panel discussion with active participation from the audience sponsored by the ISA on the topic at the 4th ISSAM Congress in Prague in February 2004.peer-reviewe

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

Prevalence of Pituitary Hormone Dysfunction, Metabolic Syndrome, and Impaired Quality of Life in Retired Professional Football Players: A Prospective Study

Hypopituitarism is common after moderate and severe traumatic brain injury (TBI). Herein, we address the association between mild TBI (mTBI) and pituitary and metabolic function in retired football players. Retirees 30–65 years of age, with one or more years of National Football League (NFL) play and poor quality of life (QoL) based on Short Form 36 (SF-36) Mental Component Score (MCS) were prospectively enrolled. Pituitary hormonal and metabolic syndrome (MetS) testing was performed. Using a glucagon stimulation test, growth hormone deficiency (GHD) was defined with a standard cut point of 3 ng/mL and with a more stringent body mass index (BMI)-adjusted cut point. Subjects with and without hormonal deficiency (HD) were compared in terms of QoL, International Index of Erectile Function (IIEF) scores, metabolic parameters, and football career data. Of 74 subjects, 6 were excluded because of significant non-football-related TBIs. Of the remaining 68 subjects (mean age, 47.3±10.2 years; median NFL years, 5; median NFL concussions, 3; mean BMI, 33.8±6.0), 28 (41.2%) were GHD using a peak GH cutoff of <3 ng/mL. However, with a BMI-adjusted definition of GHD, 13 of 68 (19.1%) were GHD. Using this BMI-adjusted definition, overall HD was found in 16 (23.5%) subjects: 10 (14.7%) with isolated GHD; 3 (4.4%) with isolated hypogonadism; and 3 (4.4%) with both GHD and hypogonadism. Subjects with HD had lower mean scores on the IIEF survey (p=0.016) and trended toward lower scores on the SF-36 MCS (p=0.113). MetS was present in 50% of subjects, including 5 of 6 (83%) with hypogonadism, and 29 of 62 (46.8%) without hypogonadism (p=0.087). Age, BMI, median years in NFL, games played, number of concussions, and acknowledged use of performance-enhancing steroids were similar between HD and non-HD groups. In summary, in this cohort of retired NFL players with poor QoL, 23.5% had HD, including 19% with GHD (using a BMI-adjusted definition), 9% with hypogonadism, and 50% had MetS. Although the cause of HD is unclear, these results suggest that GHD and hypogonadism may contribute to poor QoL, erectile dysfunction, and MetS in this population. Further study of pituitary function is warranted in athletes sustaining repetitive mTBI

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