Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.
Context: Testosterone abuse is conventionally assessed by the urinary testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered suspicious. The large variation in testosterone glucuronide (TG) excretion and its strong association with a deletion polymorphism in the uridine diphospho-glucuronosyl transferase (UGT) 2B17 gene challenge the accuracy of the T/E ratio test.Objective: Our objective was to investigate whether genotype-based cutoff values will improve the sensitivity and specificity of the test. Design:This was an open three-armed comparative study.Participants: A total of 55 healthy male volunteers with either two, one, or no allele [insertion/ insertion, insertion/deletion, or deletion/deletion (del/del)] of the UGT2B17 gene was included in the study.Intervention: A single im dose of 500 mg testosterone enanthate was administered.Main Outcome Measures: Urinary excretion of TG after dose and the T/E ratio during 15 d were calculated. Results:The degree and rate of increase in the TG excretion rate were highly dependent on the UGT2B17 genotype with a 20-fold higher average maximum increase in the insertion/insertion group compared with the del/del group. Of the del/del subjects, 40% never reached the T/E ratio of 4.0 on any of the 15 d after the dose. When differentiated cutoff levels for the del/del (1.0) and the other genotypes (6.0) were applied, the sensitivity increased substantially for the del/del group, and false positives in the other genotypes were eliminated.Conclusions: Consideration of the genetic variation in disposition of androgens will improve the sensitivity and specificity of the testosterone doping test. This is of interest not only for combating androgen doping in sports, but also for detecting and preventing androgen abuse in society. (J Clin Endocrinol Metab 93: 2500 -2506, 2008) T estosterone (T) was identified as the male sex hormone in the mid-1930s. It has been clinically used for nearly seven decades (1), primarily for androgen replacement therapy in men with androgen deficiency. Over the recent decades, testosterone and other androgens have been increasingly abused for muscle building and enhancement of physical performance (2). A recent study showed that power lifters with current or previous abuse of anabolic steroids have increased cross-sectional area of muscle
BackgroundLow serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of respiratory tract infections (RTIs). Clinical trials with vitamin D3 against various infections have been carried out but data are so far not conclusive. Thus, there is a need for additional randomised controlled trials of effects of vitamin D3 on infections.ObjectiveTo investigate if supplementation with vitamin D3 could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs.DesignA double-blind randomised controlled trial.SettingKarolinska University Hospital, Huddinge.Participants140 patients with antibody deficiency (selective IgA subclass deficiency, IgG subclass deficiency, common variable immune disorder) and patients with increased susceptibility to RTIs (>4 bacterial RTIs/year) but without immunological diagnosis.InterventionVitamin D3 (4000 IU) or placebo was given daily for 1 year.Primary and secondary outcome measuresThe primary endpoint was an infectious score based on five parameters: symptoms from respiratory tract, ears and sinuses, malaise and antibiotic consumption. Secondary endpoints were serum levels of 25-hydroxyvitamin D3, microbiological findings and levels of antimicrobial peptides (LL-37, HNP1–3) in nasal fluid.ResultsThe overall infectious score was significantly reduced for patients allocated to the vitamin D group (202 points) compared with the placebo group (249 points; adjusted relative score 0.771, 95% CI 0.604 to 0.985, p=0.04).LimitationsA single study centre, small sample size and a selected group of patients. The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level.ConclusionsSupplementation with vitamin D3 may reduce disease burden in patients with frequent RTIs.
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