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Purpose: To better understand the effects of aging, metabolic syndrome, diurnal variation, and seasonal variation on serum testosterone levels in the context of current guideline statements on testosterone deficiency., Methods: This cross-sectional study utilized the United Kingdom Biobank. Physical examination, anthropomorphic measurements, and laboratory evaluation were performed at the time of enrollment from 2006 to 2010. The primary outcomes were the effect of age, the presence of metabolic syndrome, the time of day, and the month of the year on serum testosterone levels., Results: Among 197,883 included men, the 5th, 25th, 50th, 75th and 95th percentile testosterone levels in men without metabolic syndrome were significantly higher than those in men with metabolic syndrome at every decade of life (p < 0.001). The average testosterone level within each group (men without metabolic syndrome vs. men with) was clinically similar across decade of life (12.43 in 40's 12.29 in 50's 12.24 in 60's vs. 10.69 in 40's 10.56 in 50's 10.63 in 60's respectively). Average testosterone levels decreased with blood draws later in the day ranging from 10.91 to 12.74 nmol/L (p < 0.01). Similarly, there was seasonal variation in serum testosterone ranging from 11.86 to 12.18 nmol/L (p < 0.01)., Conclusions: We found significant variation in serum testosterone according to the presence of metabolic syndrome and time of laboratory draw, but not according to age. These data challenge the prior dogma of age-related hypogonadism and favor an individualized approach towards serum testosterone measurement and interpretation. However, further studies are needed to correlate these population-based data with individuals' hypogonadal symptoms., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: To investigate the association between elevated endogenous testosterone levels and deleterious effects associated with testosterone therapy. Elevated serum testosterone levels in men receiving testosterone therapy have been associated with side effects, though precise thresholds above which these occur are unknown. Data on the association between naturally elevated endogenous testosterone levels and their physiologic effects is sparse., Methods: We examined National Health and Nutrition Examination Survey data between 2011 and 2016, analyzing men aged 18 and older not on testosterone or androgen ablation therapy, excluding men who had testosterone <300 ng/dL, to compare men with elevated testosterone (>800 ng/dL) to men with normal testosterone (300-800 ng/dL). We used multivariable logistic and linear regressions for comparison., Results: After excluding men with testosterone levels <300 ng/dL, 3673 men met inclusion criterion. Only 146 (4%) of men had a testosterone >800 ng/dL. When compared to men with normal testosterone, men with high testosterone had similar rates of sleep disorders, urinary symptoms, and depression. Men with elevated testosterone had higher hematocrit regression coefficient (βi 1.30, 95% confidence interval [CI] 0.69-1.90 P < .01), AST (βi 8.48, 95% CI 0.31-16.66, P = .04) and ALT (βi 12.23, 95% CI 0.70-23.77, P = .04) compared to men with normal testosterone., Conclusion: No association was found between higher endogenous testosterone levels and adverse events associated with testosterone therapy. Men with higher testosterone had increased hematocrit, but this was not clinically significant. This challenges what is considered a safe target for testosterone therapy and prompts future prospective studies to delineate the safety of elevated endogenous and exogenous modulated levels of testosterone., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Exercise and weight loss have been shown to improve serum testosterone (T) in obese individuals. However, the association between low T levels and guideline-based exercise thresholds has not been determined., Objective: Using the recently updated Physical Activity Guidelines Advisory Committee (PAGAC) recommendations, we sought to investigate the relationship between recommended activity levels and the prevalence of low T levels., Materials and Methods: The2011-2016 National Health and Nutrition Examination Survey (NHANES) was used to identify men ages 18 to 80 years who answered the physical activity questionnaire and underwent serum T testing. Men were categorized based on PAGAC activity level: less than recommended, recommended and greater than recommended. Multivariable logistic regressions were used to determine the association between low T (<300 ng/dL) and activity level across body mass index (BMI) categories while adjusting for potential confounders., Results: Of the 7372 men who met the inclusion criteria, the majority (4372, 59.3%) exceeded the recommended amount of activity, whereas only 2326 (31.6%) exercised less than the recommended amount. On multivariable analysis, obese men whose activity exceeded the recommended amount were less likely to have low T (OR 0.523, 95% CI 0.409-0.669, P < .001) compared with men who did not meet the recommended activity level., Discussion and Conclusions: Using a large, nationally representative cohort, we demonstrated that obese men whose activity exceeded PAGAC recommendations had a decreased likelihood of having low T levels. Given the numerous benefits of exercise, these data provide a basis for counseling obese patients regarding the association between exercise and decreased prevalence of low T., (© 2020 American Society of Andrology and European Academy of Andrology.)

Recent data have suggested that short-term NSAID use induces a state of compensated hypogonadism. Our aim was to investigate the association between chronic, regular NSAID use and compensated hypogonadism in a large, nationally representative cohort, the US National Health and Nutrition Examination Survey (NHANES) database. Men 20-80 years who answered the analgesic use questionnaire and underwent hormonal testing were included. Multivariable regression was utilised to determine the relationship between NSAID use and serum testosterone (T), anti-Mullerian hormone (AMH) and T:AMH ratio. Among 3,749 men, 505 (13.5%) reported regular NSAID use and 3,244 (86.5%) did not. Regular users had lower T (440.7 ± 27.0 vs. 557.0 ± 24.9 ng/dl, p = .005) and albumin (43.8 ± 0.2 vs. 45.1 ± 0.1, p < .001) compared to nonregular users. On multivariable analysis, only active smoking was significantly associated with T, AMH and T:AMH ratio (p < .001, p = .036 and p = .005 respectively). Regular NSAID use was not associated with T, AMH or T:AMH ratio (p = .523, p = .974, and p = .872 respectively). In this nationally representative sample of US men, regular and chronic NSAID use was not associated with alterations in T or compensated hypogonadism. These data should reassure patients and clinicians regarding the safety of NSAID use with respect to the risk of alteration in the hypothalamic-pituitary-gonadal axis., (© 2020 Blackwell Verlag GmbH.)

Purpose: We examined the relationship of the serum testosterone level to low fat, Mediterranean and low carbohydrate diets in a large, nationally representative patient sample., Materials and Methods: We queried the NHANES (National Health and Nutrition Examination Survey) from 1999 to 2000, 2003 to 2004 and 2011 to 2012. Men 18 to 80 years old who completed the 2-day dietary history and underwent serum testosterone testing were included in analysis. Diets were categorized as low fat, Mediterranean, low carbohydrate or nonrestrictive. Multivariable modeling was used to determine the relationship between diet and serum testosterone., Results: Of the 3,128 men who met study inclusion criteria 457 (14.6%) and 764 (24.4%) met the criteria for a low fat and a Mediterranean diet, respectively. Only 2 men (less than 0.1%) met the criteria for a low carbohydrate diet, which was removed from further analysis. Mean ± SD serum testosterone was 435.5 ± 6.7 ng/dl. Mean testosterone was lower among men with a low fat diet (410.8 ± 8.1 vs 443.5 ± 7.3, p=0.005) and a Mediterranean diet (412.9 ± 9.1 vs 443.5 ± 7.3, p=0.002). Multivariable analysis controlling for age, body mass index, activity level, diabetes, comorbidities and prostate cancer showed that men with a nonrestrictive diet had higher serum testosterone than those adhering to a low fat diet (ß -57.2, 95% CI -105.6 to -8.8, p <0.05)., Conclusions: Men adhering to low fat diets had lower serum testosterone levels even when controlling for comorbidities, age, body mass index and activity levels. As differences in serum testosterone between the diets were modest, the avoidance of fat restrictive diets should be weighed against the potential benefits on an individual basis.