Genetic influences on hippocampal volume differ as a function of testosterone level in middle-aged men.
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ABSTRACT:
SUBMITTER: Panizzon MS
PROVIDER: S-EPMC3230702 | biostudies-literature | 2012 Jan
REPOSITORIES: biostudies-literature
Publications
Genetic influences on hippocampal volume differ as a function of testosterone level in middle-aged men.
Panizzon Matthew S MS Hauger Richard L RL Eaves Lindon J LJ Chen Chi-Hua CH Dale Anders M AM Eyler Lisa T LT Fischl Bruce B Fennema-Notestine Christine C Franz Carol E CE Grant Michael D MD Jacobson Kristen C KC Jak Amy J AJ Lyons Michael J MJ Mendoza Sally P SP Neale Michael C MC Prom-Wormley Elizabeth E Seidman Larry J LJ Tsuang Ming T MT Xian Hong H Kremen William S WS
NeuroImage 20111001 2
The hippocampus expresses a large number of androgen receptors; therefore, in men it is potentially vulnerable to the gradual age-related decline of testosterone levels. In the present study we sought to elucidate the nature of the relationship between testosterone and hippocampal volume in a sample of middle-aged male twins (average age 55.8 years). We found no evidence for a correlation between testosterone level and hippocampal volume, as well as no indication of shared genetic influences. Ho ...[more]
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Project description:To investigate the impact of metabolic components and body composition indices on prostate volume (PV) in a population of middle-aged men receiving health check-ups.Six hundred and sixteen men receiving health assessments were stratified to large and small prostates based on the cut-off of median PV. Their demographic data, health history, and international prostate symptoms scores (IPSS) were collected. Metabolic components and body composition indices were compared between subjects with large and small prostates. Moreover, the correlations between these parameters and PV were analyzed by multivariate logistic regression.The median PV was 27 mL and mean age was 54.8 years. Subjects with large PV were older (56.5 vs. 52.7 years) and had higher serum prostate specific antigen (PSA) level (1.73 vs. 0.96 ng/mL), higher IPSS score (8.37 vs. 6.16), and higher body fat, body mass, and waist circumference (all p<0.05). In multivariate analysis, age (OR, 2.45; 95%CI, 1.74-3.45), serum PSA (OR, 2.75; 95%CI, 1.96-3.86), waist circumference (OR, 1.45; 95%CI, 1.02-2.07), fatness (OR, 1.47; 95%CI, 1.04-2.09), and body fat mass (OR, 1.43; 95%CI, 1.00-2.03) were significantly correlated with PV of study subjects. In subgroup analysis, raised waist circumference (OR, 1.89; 95%CI, 1.00-3.59) was the independent predictor of PV in subjects with bothersome lower urinary tract symptoms.Several metabolic components and body composition indices are significantly associated with PV of middle-aged men, including raised waist circumference, fatness, and body fat mass. Raised waist circumference is the only independent predictor of PV in middle-aged men with bothersome LUTS.
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Project description:BackgroundLow vitality is a common symptom of testosterone deficiency; however, clinical trial results remain inconclusive regarding the responsiveness of this symptom to hormone replacement.AimThe aim of the present study was to determine if the relationship between circulating testosterone levels and vitality would be moderated by the CAG repeat length in the androgen receptor (AR) gene, which influences the receptor's sensitivity to testosterone.MethodsWe examined 676 men in the Vietnam Era Twin Study of Aging when they were, on average, 55.4 years old (SD = 2.5). Salivary testosterone levels were measured by using 3 samples collected at waking on 3 nonconsecutive days. The average testosterone level was classified as low, normal, or high based on 1-SD cutoffs. Analyses were conducted using multilevel, mixed linear models, which accounted for the nonindependence of the twin data, and adjusted for the effects of age, ethnicity, BMI, chronic health conditions, depressive symptoms, and sleep quality.OutcomesVitality was measured using the 36-item Short Form (SF-36) vitality subscale.ResultsWe observed a significant interaction between salivary testosterone and the AR-CAG repeat length. When the repeat length was short, men with low testosterone had significantly lower vitality. As the AR-CAG repeat length increased, the magnitude of the testosterone effect decreased.Clinical translationThe observed interaction between testosterone and variation in the AR gene suggests that men with more sensitive ARs, as indicated by a shorter AR-CAG repeat, are more likely to experience symptoms of age-related testosterone deficiency.Strengths & limitationsStrengths of the present study include our use of a large community-based sample, the use of multiple testosterone measurements, and the availability of a comprehensive set of covariates that may impact the association of interest. Limitations include the homogeneous nature of the sample with respect to ethnicity, the brevity of the 36-item Short Form vitality subscale, and our inability to establish change in testosterone levels because of the cross-sectional nature of data.ConclusionsThe association between testosterone and vitality appears to be clinically meaningful and is in part dependent on variation in the AR gene. Panizzon MS, Bree K, Hsieh T-C, et al. Genetic Variation in the Androgen Receptor Modifies the Association Between Testosterone and Vitality in Middle-Aged Men. J Sex Med 2020;17:2351-2361.
| S-EPMC7718411 | biostudies-literature
Project description:ImportanceRecent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk.ObjectiveTo test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume.Design, setting, and participantsDouble-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014.InterventionTestosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months.Main outcomes and measuresThe primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis).ResultsOf 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group.Conclusions and relevanceAmong older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.Trial registrationclinicaltrials.gov Identifier: NCT00799617.
| S-EPMC5465430 | biostudies-literature