Multiple factors place adults with haemophilia at risk for depression. Health outcomes can be compromised in depressed patients secondary to increased risk taking behaviour and poor compliance with treatment recommendations. To assess the prevalence and risk factors associated with depression in adult patients with haemophilia treated at a haemophilia treatment centre. Adults with haemophilia were screened for depression during their annual clinic visit using the Patient Health Questionnaire 9 (PHQ-9), a validated tool for depression screening in adults. Depression was defined as a PHQ-9 score ≥ 5. Risk factors associated with depression were collected by chart review and correlated with depression scores. A total of 41 adult patients consented to the study and 37% met criteria for depression. Fifty-three per cent of patients with depression reported moderate to severe symptoms of depression (PHQ-9 score >10). Seventy-six per cent of patients with depression reported suffering functional impairment due to their depressive symptoms. Lack of social support and unemployment were significantly associated with higher PHQ-9 scores (P = 0.04 and P = 0.01 respectively). Adult patients with haemophilia have a high prevalence of depression. The addition of depression screening to the comprehensive care of adults with haemophilia may result in improved overall health outcomes and treatment adherence.

We have investigated the influence of oral\ud miconazole administration on the urinary concentrations of\ud endogenous anabolic androgenic steroids of doping relevance,\ud specifically considering all these compounds routinely monitored in doping control analysis, in the framework of the\ud steroidalmodule of the ‘‘athlete biologicalpassport’’, and other\ud steroids, including dehydroepiandrosterone, 5a-dihydrotestosterone, and the hydroxylated metabolites recently\ud proposed as additional markers of the intake of testosteronerelated steroids (16a-hydroxy-androsterone, 16a-hydroxyetiocholanolone, 6b-hydroxy-androsterone, 6b-hydroxy-etiocholanolone, 7a-hydroxy-dehydroepiandrosterone, and 7bhydroxy-dehydroepiandrosterone). Urinary concentrations of\ud the final metabolic products of the glucocorticoid biosynthetic\ud pathways (11b-hydroxy-androsterone and 11b-hydroxy-etiocholanolone, the formerly used as an endogenous reference\ud compound for the gas chromatography–combustion-isotope\ud ratio mass spectrometry confirmation analysis) were also\ud monitored. Two healthy Caucasian volunteers exhibiting\ud physiologically high testosterone/epitestosterone ratios and\ud elevated concentrations of the main target steroids were\ud selected for the study. Miconazole was administered orally\ud (500 mg/day) for 1 week. Multiple urine samples were\ud collected for 1 week before and during the treatment, and\ud analyzed according to a validated analytical procedure based\ud on gas chromatography–electron ionization-mass spectrometry in selected ion monitoring mode. Our results indicated that\ud oral administration of miconazole decreased the urinary concentrations of androsterone, and to a lesser extent, of etiocholanolone (both detected as the sum of free and glucuronated\ud steroids), and consequently the androsterone/testosterone and\ud androsterone/etiocholanolone ratios. Furthermore, the urinary\ud concentrations of 16a-hydroxy-etiocholanolone, 16a-hydroxy-androsterone, 7b-hydroxy-dehydroepiandrosterone,\ud 6b-hydroxy-etiocholanolone, 7a-hydroxy-dehydroepiandrosterone, 6b-hydroxy-androsterone, 11b-hydroxy-androsterone,\ud and 11b-hydroxy-etiocholanolone were significantly suppressed. This evidence suggests the potential intake of\ud miconazole whenever the urinary steroid profile is characterized by abnormally low concentrations of the above-mentioned steroids

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Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. Following the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“oral turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including the synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights into the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations to the D-ring.

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Rationale Although the metabolism of methyltestosterone (MT) has been extensively studied since the 1950s using different techniques, the aim of this study was to investigate the hydroxylation in positions C2, C4 and C6 after in vitro experiments and in vivo excretion studies using gas chromatography time‐of‐flight (GC/TOF) and gas chromatography/tandem mass spectrometry (GC/MS/MS). The results could be influenced by the mass spectrometric analyser used. Methods Incubations were carried out with human liver microsomes and six enzymes belonging to the cytochrome P450 family using MT as a substrate. The trimethylsilyl derivatives of the samples were analysed using GC/TOF and GC/MS/MS once the correct MS/MS transitions had been selected, mainly for 6‐hydroxymethyltestosterone (6‐OH‐MT) to avoid artefact interferences. A urinary excretion study was then performed after the administration of a 10 mg single oral dose of MT to a volunteer. Results The formation of hydroxylated metabolites of MT in the C6, C4 and C2 positions after both in vitro and in vivo experiments was observed. Sample evaluation using GC/TOF showed an interference for 6‐OH‐MT that could only be resolved in GC/MS/MS by monitoring specific transitions. The transitory detection of these hydroxylated metabolites in urine agrees with previous investigations that had described this metabolic route as being of little significance. Conclusions In doping analysis, the formation of 4‐hydroxymethyltestosterone (oxymesterone) from MT cannot be underestimated. Although it is only detected as a minor and short‐term excretion metabolite, it cannot be overlooked as it was found in both in vitro and in vivo experiments. The use of a combination of different mass spectrometric instruments allowed reliable conclusions to be reached, and it was shown that special attention must be given to artefact formation.

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