The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebocontrolled study of testosterone treatment (gel) was done on 38 men, aged 60-78 years, with bioavailable testosterone <7.3 nmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b=1.9 kg, p=0.003) increased while HDL-cholesterol (b=−0.12 mmol/l, p=0.043) and TFM decreased (b=−1.2 kg, p=0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b=5.65 mg/min/m 2 , p=0.045) increased and basal glucose oxidation (b=−9.71 mg/min/m 2 , p = 0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b=−0.01mg/min/m 2 , p=0.92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.

Objective: Testosterone therapy increases lean body mass and decreases total fat mass in aging men with low normal testosterone levels. The major challenge is, however, to determine whether the metabolic consequences of testosterone therapy are overall positive. We have previously reported that 6-month testosterone therapy did not improve insulin sensitivity. We investigated the effect of testosterone therapy on regional body fat distribution and on the levels of the insulin-sensitizing adipokine, adiponectin, in aging men with low normal bioavailable testosterone levels. Design: A randomized, double-blinded, placebo-controlled study on 6-month testosterone treatment (gel) in 38 men, aged 60-78 years, with bioavailable testosterone !7.3 nmol/l, and a waist circumference O94 cm. Methods: Central fat mass (CFM) and lower extremity fat mass (LEFM) were measured by dual X-ray absorptiometry. Subcutaneous abdominal adipose tissue (SAT), visceral adipose tissue (VAT), and thigh subcutaneous fat area (TFA) were measured by magnetic resonance imaging. Adiponectin levels were measured using an in-house immunofluorometric assay. Coefficients (b) represent the placebocontrolled mean effect of intervention. Results: LEFM was decreased (bZK0.47 kg, PZ0.07) while CFM did not change significantly (bZK0.66 kg, PZ0.10) during testosterone therapy. SAT (bZK3.0%, PZ0.018) and TFA (bZK3.0%, P!0.001) decreased, while VAT (bZ1.0%, PZ0.54) remained unchanged. Adiponectin levels decreased during testosterone therapy (bZK1.3 mg/l, PZ0.001). Conclusion: Testosterone therapy decreased subcutaneous fat on the abdomen and lower extremities, but visceral fat was unchanged. Moreover, adiponectin levels were significantly decreased during testosterone therapy.

SAT rather than VAT was inversely associated with adiponectin levels, and, interestingly, fat on the lower extremities was positively associated with adiponectin. Focusing on insulin resistance, SAT rather than VAT and TFA independently predicted a higher HOMA-IR. The observation that adiponectin was independently associated with lower HOMA-IR must be repeated in other populations.

This study aimed to review digital interventions in the treatment of Autism Spectrum Disorder (ASD). A systematic review and meta-analysis was conducted. Nineteen studies were included. The interventions aimed to improve social skills (n=11), developmental skills (n=2) and 6 other different targets. Technology used were computer programs (n=14), tablet apps (n=3), a robot (n=1) and an interactive DVD (n=1). The meta-analysis resulted in an overall effect size (Cohen's d) of 0.32 [0.12-0.51], indicating a small effect. Heterogeneity between studies was high (I 2 =100%), limiting the generalization of results. Therefore, we recommend larger RCT studies, and guidelines for the development of trials evaluating digital interventions for ASD, for making comparison of future studies possible. Autism spectrum disorder (ASD) is characterized by difficulties in social communication and unusually restricted, repetitive behavior and interests. The most effective interventions are behavioral and educational (Lai, Lombardo, & Baron-Cohen, 2014). However, many families are unable to access interventions due to time consumption and substantial costs (Peters-

The cardiovascular effects of testosterone treatment are debated. Osteoprotegerin (OPG) is an independent marker of cardiovascular risk. We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels. A randomized, double-blinded, placebo-controlled study of 6 months testosterone therapy (gel) in 38 men aged 60-78 years with bioavailable testosterone <7.3 nmol/l and waist circumference >94 cm was performed. Clinical evaluation, OPG, and C-reactive protein (CRP) measurements were carried out. Lean body mass (LBM), total fat mass, and bone mineral density (BMD) were established by dual X-ray absorptiometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by magnetic resonance imaging. Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased LBM (Δ LBM positive), n=14. Data are presented as median (interquartile range). Testosterone therapy decreased total fat mass and SAT, whereas VAT was unchanged (n=38). OPG levels decreased during testosterone therapy (from 2.0 (1.9-2.5) to 1.9 (1.6-2.2) ng/ml, p<0.05 vs. placebo), whereas CRP levels were unchanged (n=38). In responders to testosterone therapy (n=14), ΔOPG levels were inversely associated with ΔSAT (r= - 0.60, p=0.03) and positively associated with ΔVAT (r=0.56, p=0.04). OPG levels decreased during testosterone therapy suggesting decreased cardiovascular risk. Decreased OPG levels were associated with changes in regional fat distribution and future studies are needed to further evaluate the association between OPG and regional fat mass distribution.

Objective: This study examined the validity of childhood depression diagnoses in the Danish Psychiatric Central Research Register (DPCRR) and identified predictors of validity. Methods: A nationwide random sample of 500 children (6-17 years) diagnosed with depression between 1996 and 2016 was identified in the DPCRR. Psychiatric hospital records were reviewed and rated using an online checklist. The primary outcome was whether depressive symptoms and functional impairment documented in hospital records justified a depressive disorder diagnosis based on ICD-10 or DSM-5 diagnostic criteria. Diagnostic validity was calculated as the positive predictive value. Binary logistic regression analysis was used to identify potential predictors of diagnostic validity, and these were included in a multiple logistic regression. Results: Psychiatric hospital records were available for 393 patients (78.6%). The documentation in the records justified an ICD-10 depressive episode diagnosis in 72.8%, and DSM-5 major depressive disorder in 73.3% of the patients registered with a depression diagnosis. We identified three predictors of diagnostic validity: (i) The validity increased almost linearly from 2000 to 2016 (OR 1.14, 95% CI 1.07-1.20, p < 0.001), (ii) antidepressant use was associated with increased diagnostic validity (OR 2.27, 95% CI 1.35-3.82, p = 0.002) and (iii) emergency department admission predicted low diagnostic validity (OR 0.33, 95% CI 0.12-0.93, p = 0.036).

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