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The HOMA-IR, E2 and E2/T of the type 2 diabetes group and DO group were significantly increased, whereas the bone mineral density, ISI, T and sex hormone binding globulin were decreased compared with those of the normal control group. Serum testosterone levels of the type 2 diabetes group and DO group were negatively correlated to the HOMA-IR (r = -0.496, -0.506; P < 0.05), whereas they were positively correlated to the fasting insulin (r = 0.281, 0.292; P < 0.05) and ISI (r = 0.364, 0.403; P < 0.05). testosterone.

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Of the 321,674 total men, 10,133 (3.2%) underwent testing with a serum total testosterone (mean age of 55.2 ± 14.1 years). The frequency of testing increased from 2.5% to 3.6% during the study period (P < 0.001). Multivariable analysis demonstrated that TM were significantly (P < 0.001) more likely to be Caucasian and have increased body mass index. In addition, TM were significantly more likely to have comorbid conditions including decreased libido (adjusted odds ratio [aOR] 10.0, 95% confidence interval [CI] 8.5, 11.7), infertility (aOR 4.8, 95% CI 3.6, 6.6), erectile dysfunction (aOR 3.6, 95% CI 3.4, 3.8), osteoporosis (aOR 3.3, 95% CI 2.8, 3.8), depression (aOR 1.7, 95% CI 1.6, 1.8), prostate cancer (aOR 1.7, 95% CI 1.5, 1.8), hypertension (aOR 1.3. 95% CI 1.2, 1.4), chronic obstructive pulmonary disease (aOR 1.2, 95% CI 1.0, 1.4), and benign prostatic hyperplasia (aOR 1.2, 95% CI 1.1, 1.2). Among TM, only 889 (9%) men underwent testing between 7 am and 12 pm. testosterone.

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Accurately assessing the contribution of cytochrome P450 (P450) isoforms to overall metabolic clearance is important for prediction of clinical drug-drug interactions (DDIs). The relative activity factor (RAF) approach in P450 reaction phenotyping assumes that the interaction between P450-selective probes and testing systems is the same as the interaction of drug candidate with those systems. To test this assumption, an intersystem clearance ratio (ICR) was created to evaluate the difference in values between RAF-scaled intrinsic clearance (CLint) and measured CLint in human liver microsomes (HLMs). The RAF value for CYP3A4 or CYP2C9 derived from a particular P450-selective probe reaction was applied to calculate RAF-scaled CLint for other probe reactions of the same P450 isoform in a crossover manner and compared with the measured HLM CLint When RAF derived from midazolam or nifedipine was used for CYP3A4, the ICR for testosterone 6β-hydroxylation was 31 and 25, respectively, suggesting significantly diverse interactions of CYP3A4 probes with the testing systems. Such ICR differences were less profound among probes for CYP2C9. In addition, these RAF values were applied to losartan and meloxicam, whose metabolism is mostly CYP2C9 mediated. Only using the RAF derived from testosterone for CYP3A4 produced the expected CYP2C9 contribution of 72%-87% and 47%-69% for metabolism of losartan and meloxicam, respectively. RAF derived from other CYP3A4 probes would have attributed predominantly to CYP3A4 and led to incorrect prediction of DDIs. Our study demonstrates a significant impact of probe substrate selection on P450 phenotyping using the RAF approach, and the ICR may provide a potential solution. testosterone.

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Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level. Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in serum are associated with serum concentrations of male reproductive hormones and semen quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP on semen quality and reproductive hormones. A cross-sectional sample of 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men gave semen and blood samples and were interviewed. Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography tandem mass spectrometry in serum. The metabolites were summed according to their molar weight. We observed significant inverse associations between serum levels of the metabolites, the proxies and serum testosterone. Negative associations were also discovered between some metabolites and sex hormone-binding globulin, semen volume and total sperm count. Findings are compatible with a weak anti-androgenic action of DEHP metabolites, but less so for DiNP metabolites. Metabolic pathways differed significantly between the three study sites, but without major effect on semen quality or reproductive hormones. testosterone.

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The ferritin is an important participant of iron-storage but its regulation and related factors were not well defined. The present objective was to explore the potential association between serum ferritin levels and sex hormones. testosterone.

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We investigated the renal effects of a high-intensity exercise (HIE) program based on strength training. 20 Wistar rats were randomly assigned to 2 experimental groups performing HIE or control over 12 weeks. Urinary volume, pH, citrate and calcium, and plasma urea, total proteins, creatinine, albumin, lactate dehydrogenase, creatine kinase (CK), calcium, magnesium, corticosterone and testosterone were measured. We also studied renal morphology with the Fibrosis HR(®) software. Plasma urea and CK concentrations were higher in the HIE compared to the control group (p < 0.05), whereas plasma creatinine was lower (p < 0.01). Plasma corticosterone was higher (p < 0.05) and testosterone lower (p < 0.01) in the HIE group. Except for the higher urinary volume found in the HIE group (p < 0.05), no differences between groups were observed in the rest of urinary parameters analyzed. Renal interstitial connective tissue was ~30% higher in the HIE group (p < 0.05). Glomerular tufts and mesangial areas were also higher in the HIE group (all, p < 0.05). No differences between groups were observed in the glomerular area. Overall, HIE promoted a worse morphological renal profile that might be associated with a higher risk for incidence of kidney disease in the long-term. The stress induced by the type of exercise performed could be on the basis of this worse morphological renal status. testosterone.

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