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

Abstract:The main aim of this study was to test the hypothesis whether 25-hydroxyvitamin D (25OHD) levels <50 nmol/L at baseline could predict statin-induced myopathy during the course of treatment. In addition, we analysed the association between a genetic polymorphism in the vitamin D receptor (VDR) and the risk of statin-induced myopathy. We used serum samples from a prospective, observational study in statin-treated patients in Sweden who were thoroughly followed with interviews and questionnaires regarding muscular symptoms (n = 127). In this cohort, 16 developed muscular symptoms and 111 had no muscular symptoms associated with statin treatment during the first year of follow-up. Patients with 25OHD levels <50 nmol/L before starting on statin treatment had four times higher risk of developing muscular symptoms compared with individuals having 25OHD levels >50 nmol/L (RR 4.2; 95% CI 1.7-10.2; p < 0.01). The mean levels of 25OHD at baseline were 50 AE 4 nmol/L among patients developing myopathy and 60 AE 2 nmol/L among patients without myopathy (p < 0.01). Individuals homozygous for the C allele in the VDR polymorphism TaqI (rs731236) had a four times higher risk of developing muscular symptoms; (RR 4.37, 95% CI 1.9-10.1, p < 0.01). In conclusion, 25OHD levels <50 nmol/L might be a useful marker to predict muscular adverse events during statin treatment. In addition, the finding that the VDR polymorphism TaqI was associated with myopathy may indicate a causal relationship between vitamin D function and myopathy, but larger studies are needed before firm conclusions can be drawn.

Previous in vitro studies have shown that microRNA‐27b (miR‐27b) may regulate mRNA levels of CYP3A4, vitamin D receptor (VDR), and Peroxisome proliferator‐activated receptor α (PPAR α) as well as CYP3A4 protein expression and activity. In vitro studies have also shown that vitamin D may affect the expression of CYP3A4. The primary aim of this pilot study was to investigate the association between miR‐27b and CYP3A expression and activity. The secondary aim was to investigate the association between 25‐hydroxy vitamin D in serum and CYP3A activity. Mi‐RNA‐27b was quantified using real‐time PCR in serum samples (n = 28) and 25‐hydroxyvitamin D was measured and correlated with the levels of the endogenous CYP3A activity marker 4β‐hydroxycholesterol. In addition, the correlation between miR‐27b and CYP3A activity, measured by dextromethorphan N‐demethylation and 6β‐hydroxylation of testosterone and the gene expression of CYP3A4, VDR and PPAR α were assessed in 20 human liver samples. A significant association between circulatory miR‐27b levels and 4β‐hydroxycholesterol ratio was found; P = 0.04, and between hepatic miR‐27b levels and CYP3A activity, measured by dextromethorphan N‐demethylation in human liver (P = 0.04). There was no association between hepatic miR‐27b and mRNA levels of CYP3A4, VDR or PPAR α. There was a significant association between serum 25‐hydroxyvitamin D levels and 4β‐hydroxycholesterol ratio, P = 0.002. In conclusion, this pilot‐study supports the hypothesis that miR‐27b levels as well as 25‐hydroxyvitamin D may affect CYP3A activity in vivo. The results indicate that miR‐27b exerts its inhibitory effect on a translational level rather than affecting mRNA levels.