Transgender healthcare: metabolic outcomes and cardiovascular risk.

Transgender identity is often associated with gender dysphoria and minority stress. Gender-affirming hormone treatment (GAHT) includes masculinising or feminising treatment and is expected to be lifelong in most cases. Sex and sex hormones have a differential effect on metabolism and CVD in cisgender people, and sex hormone replacement in hypogonadism is associated with higher vascular risk, especially in ageing individuals. Using narrative review methods, we present evidence regarding metabolic and cardiovascular outcomes during GAHT and propose recommendations for follow-up and monitoring of metabolic and cardiovascular risk markers during GAHT. Available data show no increased risk for type 2 diabetes in transgender cohorts, but masculinising GAHT increases lean body mass and feminising GAHT is associated with higher fat mass and insulin resistance. The risk of CVD is increased in transgender cohorts, especially during feminising GAHT. Masculinising GAHT is associated with a more adverse lipid profile, higher haematocrit and increased BP, while feminising GAHT is associated with pro-coagulant changes and lower HDL-cholesterol. Assigned male sex at birth, higher age at initiation of GAHT and use of cyproterone acetate are separate risk factors for adverse CVD markers. Metabolic and CVD outcomes may improve during gender-affirming care due to a reduction in minority stress, improved lifestyle and closer surveillance leading to optimised preventive medication (e.g. statins). GAHT should be individualised according to individual risk factors (i.e. drug, dose and form of administration); furthermore, doctors need to discuss lifestyle and preventive medications in order to modify metabolic and CVD risk during GAHT. Follow-up programmes must address the usual cardiovascular risk markers but should consider that biological age and sex may influence individual risk profiling including mental health, lifestyle and novel cardiovascular risk markers during GAHT.

Acromegaly management in the Nordic countries: A Delphi consensus survey.

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

Educational outcomes and the role of comorbidity among adolescents with type 1-diabetes in Denmark.

AIMS: To examine educational outcomes among adolescents with type 1 diabetes and determine the role of comorbidity. METHODS: We conducted a nationwide register-based cohort study including 3370 individuals born between 1991 and 2003 and diagnosed with type 1 diabetes before the age of 16. They were all matched with up to four individuals without type 1 diabetes on age, gender, parents' educational level and immigration status. Information on comorbidity was based on hospital diagnoses. The individuals were followed in registers to determine whether they finished compulsory school (9th grade, usually at the age of 15-16 years), and were enrolled in secondary education by age 18 years. RESULTS: Individuals with type 1 diabetes were more likely not to complete compulsory school (OR 1.44, 95% CI 1.26-1.64), and not being enrolled in an upper secondary education by age 18 (OR 1.50, 95% CI 1.31-1.73) compared to their peers. A total of 1869 (56%) individuals with type 1 diabetes were registered with at least one somatic (n = 1709) or psychiatric comorbidity (n = 389). Those with type 1 diabetes and psychiatric comorbidity were more likely not to complete compulsory school (OR 2.47, 95% CI 1.54-3.96), and not being enrolled in an upper secondary education by age 18 (OR 3.66, 95% CI 2.27-5.91) compared to those with type 1 diabetes only. Further, there was a tendency towards an association between having somatic comorbidity and adverse educational outcomes (OR 1.25, 95% CI 0.97-1.63; OR 1.26, 95% CI 0.95-1.66) among adolescents with type 1 diabetes. The associations differed markedly between diagnostic comorbidity groups. CONCLUSION: Type 1 diabetes affects educational attainment and participation among adolescents. Psychiatric comorbidity contributes to adverse educational outcomes in this group, and there is a tendency that somatic comorbidity also plays a role.

Formation of ß-Configured Thioglycosides of d-Glucosamine and d-Galactosamine and Synthesis of Protected Human Milk Oligosaccharides.

We report on the stereoselective multigram scale preparation of cyclohexyl- and phenyl thioglycosides of 2-azido-2-deoxy-ß-d-gluco- and galactopyranosides from d-N-acetylglucosamine using a catalytic and solvent-free method. Two of the prepared building blocks were used as key intermediates for the synthesis of human milk oligosaccharides LNT and LNnT in their protected form.

Effects of testosterone therapy on constructs related to aggression in transgender men: A systematic review.

BACKGROUND: Transgender men are assigned female sex at birth, but identify as men. The anabolic and androgenic sex hormone testosterone has been positively associated with aggression. Therefore, transgender men are warned of increasing aggression when initiating testosterone therapy. AIM: To explore the literature regarding the effects of testosterone therapy on aggression-related constructs in transgender men. METHODS: Following PRISMA-guidelines, PsycINFO, MEDLINE®, EMBASE, and PubMed® were searched in November 2019. Risk of bias was analyzed using the Newcastle-Ottawa-Scale, and result-synthesis was grouped by aggression-outcome. RESULTS: Seven prospective cohort studies investigating aggression-dimensions pre- and post-testosterone therapy, reporting on data from 664 transgender men, were eligible. The studies had moderate to high risk of bias due to non-randomization, lack of appropriate control groups, and reliance on self-report. The behavioral tendency to react aggressively increased in three studies out of four (at three months follow-up), whereas only one study out of five found angry emotions to increase (at seven months follow-up). In contrast, one out of three studies reported a decrease in hostility after initiation of testosterone therapy. The remaining studies found no change in aggressive behavior, anger or hostility during hormone therapy. DISCUSSION AND CONCLUSION: Four out of seven studies reported an increase in aggression-related constructs, while one study reported a decrease. In all studies reporting changes, the follow-up period was less than 12 months, indicating that gender-affirming testosterone therapy could have a short-term impact on aggression-related constructs. However, the available studies carried a risk of bias, which indicates a need for further research.

Risk of adverse perinatal outcomes in infants born to mothers with mental health conditions.

INTRODUCTION: Maternal mental health conditions have been shown to affect perinatal outcomes negatively. However, knowledge on the impact of different types and severities of maternal mental health conditions is needed. The objective of this study was to determine the association between maternal mental health status and perinatal health outcomes in the infant. MATERIAL AND METHODS: This register-based cohort study included all live-born infants in Denmark born between 2000 and 2016. Exposed infants were grouped based on whether the mothers received mental health care in primary care settings only (minor conditions) or required specialized psychiatric intervention (moderate-severe conditions) within 12 months before childbirth. Modified Poisson regression analyses were applied to produce adjusted risk ratios (aRRs) for each perinatal outcome of interest. The primary outcomes were neonatal mortality, 5-minute Apgar scores <7 and <4 and newborn hospital admission during the neonatal period. Secondary outcomes included several neonatal morbidities such as respiratory distress syndrome and abstinence syndrome. RESULTS: A total of 952 071 infants were included in the analysis; 4.0% had mothers with minor mental health conditions and 2.9% had mothers with moderate-severe conditions. The risk of neonatal death in exposed infants was aRR 1.08 (95% CI 0.93-1.27) for minor mental health conditions and aRR 0.93 (95% CI 0.78-1.11) for moderate-severe conditions. Both exposure groups had increased risks of 5-minute Apgar scores <7 (minor: aRR 1.28, 95% CI 1.16-1.41; moderate-severe: aRR 1.49, 95% CI 1.34-1.66); 5-minute Apgar scores <4 (minor: aRR 1.10, 95% CI 0.93-1.30; moderate-severe: aRR 1.18, 95% CI 0.98-1.43), and hospital admission during the neonatal period (minor: aRR 1.20, 95% CI 1.17-1.23; moderate-severe: aRR 1.22, 95% CI 1.19-1.26) along with several neonatal morbidities. An explicit high risk was seen for abstinence syndrome (minor: aRR 10.30, 95% CI 8.40-12.63; moderate-severe: aRR 12.13, 95% CI 10.17-15.67). CONCLUSIONS: Infants of mothers with moderate-severe and minor mental health conditions were at increased risks of multiple adverse perinatal outcomes. Effective supportive interventions to improve outcomes in both groups are needed.

Effect of Metformin vs. Placebo in Combination with Insulin Analogues on Bone Markers P1NP and CTX in Patients with Type 2 Diabetes Mellitus.

Preclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and insulin before entering the study. Bone formation and resorption were assessed by measuring, N-terminal propeptide of type I procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) at baseline and end of study. The influence of gender, age, smoking, body mass index (BMI), T2DM duration, glycosylated hemoglobin A1c (HbA1c), c-reactive protein (CRP) and insulin dosage was also included in the analyses. The levels of bone formation marker P1NP and bone resorption marker CTX increased significantly in both groups during the trial. P1NP increased less in the Metformin + Insulin compared to the placebo + insulin group (p = 0.001) (between group difference change), while the increases in CTX levels (p = 0.11) were not different. CRP was inversely associated (p = 0.012) and insulin dosage (p = 0.011) was positively related with change in P1NP levels. BMI (p = 0.002) and HbA1C (p = 0.037) were inversely associated with change in CTX levels. During 18 months of treatment with metformin or placebo, both in combination with insulin, bone turnover increased in both groups. But the pattern was different as the bone formation marker (P1NP) increased less during Metformin + Insulin treatment, while change in bone resorption (CTX) was not significantly different between the two groups.

Progression in risk factors during 36 years of follow-up and prediction of carotid intima-media thickness in a large cohort of adults with and without diabetes.

Carotid intima-media thickness (IMT) can assess the cumulative effect of atherosclerotic risk factors and provides an independent predictor of future cardiovascular (CV) risk. The aim of this study was to investigate the progression of conventional risk factors in 933 long-term survivors from a Danish cohort with and without diabetes mellitus (DM) as predictors for attained carotid IMT during 35.6 (0.7) years of follow-up. Persons who participated in the first, the last and one of the intermediate rounds of the Copenhagen City Heart Study, and who had had an ultrasound-derived measure of the carotid IMT performed at the last examination were included in the analyses. The risk factors varied between persons with and without DM during the 36 years, but the difference in blood pressure disappeared in the fifth examination, where, in addition, total cholesterol was found to be lower in persons with DM. In this cohort there were no difference in attained carotid IMT between persons with and without DM at the last examination. The following risk factors were found to best predict carotid IMT: age, maximum systolic BP, average systolic BP, average BMI, minimum BMI, sex and years of smoking. The prediction of carotid IMT was clinically poor with a root mean-squared error of prediction (RMSEP) of 0.134 mm and a 95% prediction error probability interval of (-0.22; 0.30). Furthermore, the distribution of prediction errors was skewed to the right indicating that the prediction errors were larger among persons with high carotid IMT.

Disruption, worries and autonomy in the everyday lives of adolescents with type 1 diabetes and their family members: A qualitative study of intrafamilial challenges.

AIM: To explore daily life with type 1 diabetes in families with an adolescent with type 1 diabetes. BACKGROUND: Management of adolescent type 1 diabetes is carried out in the context of everyday life, thus involving and affecting the entire family. Type 1 diabetes causes disruption of family life, but the specific experiences and challenges of adolescents with type 1 diabetes, siblings and parents are not well-explored. Specifically, research is lacking on the siblings' experience of adolescents with type 1 diabetes. DESIGN: A qualitative design using participatory workshops. METHODS: A sample of 21 families comprising adolescents with type 1 diabetes (aged 8-18) (N = 20), their parents (N = 29) and siblings (N = 10) participated in four workshops exploring everyday life in families with adolescent diabetes from the perspective of all family members. Data were analysed using systematic text condensation. The COREQ checklist was used preparing the manuscript. RESULTS: Family life with type 1 diabetes was characterised by three overarching themes: (a) the perpetual challenges and disruptive nature of life with diabetes, (b) different ways of worrying about diabetes and (c) diabetes autonomy and emancipation from parents. All family members' lives were marked by these aspects, however in different ways and to varying degrees. CONCLUSIONS: Our findings emphasise that type 1 diabetes is indeed a family illness affecting all family members. The study provides insight into the unique experiences of adolescents with diabetes, their parents and siblings, all of whom encounter diabetes-related challenges in their daily lives. RELEVANCE TO CLINICAL PRACTICE: The findings call for the inclusion of all family members of adolescents with type 1 diabetes in both research and healthcare practice. Family-oriented approaches targeting adolescents with diabetes as well as their parents and siblings will enable provision of nursing care that can meet the needs of the entire family.

Modern tragedies in self-help literature, blogs and online universes: conceptions of resilience as a literary phenomenon.

Focusing on the configuration of the relationship between fate and freedom of action, this article analyses recent self-help literature and online communities, particularly the genre that centres on the concept of resilience. The selected works and websites all address readers who suffer from depression, anxiety and stress. The article focuses on how the relationship between fate and freedom is represented in three literary figures: the reader, who is promised recovery; the narrator, who promises to save the reader from the mental illnesses; and the plot that the reader forms by his or her personal thoughts, feelings and experiences. Furthermore, fate and freedom will be analysed in a series of allegories and metaphors. We argue that each literary figure reflects a radical understanding of individual autonomy, that is, freedom of action. However, we also argue that each literary figure has a shadowy disadvantage, which activates a tragic reversal of fate. The article analyses how this self-help genre reflects a notion of tragedy in relation to mental suffering.

Patterns and predictors for prescription of psychotropics and mood-stabilizing antiepileptics during pregnancy in Denmark 2000-2016.

AIMS: To analyse prescribing patterns during pregnancy for antipsychotics (APs), antidepressants (ADs) and mood-stabilizing antiepileptics (AEDs) in Denmark from 2000 to 2016. METHODS: Data were obtained from the Danish Medical Birth Register, the Register for Legally Induced Abortions, the Danish National Patient Register and the Register of Medicinal Product Statistics. Data were linked through a unique personal identifier by Statistics Denmark. RESULTS: The use of APs increased 2.5-fold from a prevalence of 1.5 per 1000 pregnancies to 3.8 for pregnancies ending in a delivery. Use of mood-stabilizing AEDs increased from a prevalence of 0.1 to 2.1 during the study period. The prevalence for APs and mood-stabilizing AEDs was nearly twice as high for pregnancies ending in miscarriage or termination compared to pregnancies ending in delivery. A marked increase in the prevalence of ADs use during pregnancy was seen from 2000-2011 (from 6 to 41 per 1000 pregnancies ending in a delivery) but appears slightly in decline. Age, smoking, obesity and social status were generally associated with increased use of psychotropic drugs. CONCLUSIONS: The use of APs, ADs and mood-stabilizing AEDs during pregnancy has increased substantially in Denmark from 2000-2016. The use of ADs appears to be slightly in decline since 2011.

Carotid intima media thickness and ankle brachial index are inversely associated in subjects with and without diabetes.

Carotid intima-media thickness (IMT) and ankle brachial index (ABI) are non-invasive indicators of generalised atherosclerosis. The aim was to determine the association between carotid IMT and ABI in subjects with and without diabetes mellitus (DM), and to analyse specific age change-points. We included 2744 subjects from the Copenhagen City Heart Study (mean age (SD) 56.6 (17.2) years, 56.8% women and body mass index (BMI) 25.4 (4.1) kg/m2). Carotid IMT and ABI measurements were performed during the fifth examination. Of the 2744 subjects, 125 subjects (4.6%) had DM. Average carotid IMT was 0.667 (0.145) mm and ABI was 1.06 (0.14). Subjects with DM were older, had higher BMI and systolic blood pressure (SBP) (all p < .001). Carotid IMT was higher in subjects with DM (0.754 (0.150) mm) compared to subjects without DM (0.662 (0.144) mm) (p < .001), whereas there was no difference in ABI between the two groups. ABI was inversely associated with carotid IMT (slope = -0.17 [-0.207; -0.137] (p < .001). The association remained significant after adjustment for risk factors both in subjects with DM (slope = -0.168 [-0.328; -0.007], p = .040), and in subjects without DM (slope = -0.100 [-0.148; -0.052], p < .001), with a stronger effect of carotid IMT on ABI among subjects with DM. Carotid IMT and ABI were inversely associated in subjects with DM and without DM, but with a stronger effect in subjects with DM. Age and ABI revealed a change-point with a stronger inverse association among subjects aged >60 years.

Are freestanding midwifery units a safe alternative to obstetric units for low-risk, primiparous childbirth? An analysis of effect differences by parity in a matched cohort study.

BACKGROUND: Intrapartum complications and the use of obstetric interventions are more common in primiparous childbirth than in multiparous childbirth, leading to concern about out of hospital birth for primiparous women. The purpose of this study was to determine whether the effect of birthplace on perinatal and maternal morbidity and the use of obstetric interventions differed by parity among low-risk women intending to give birth in a freestanding midwifery unit or in an obstetric unit in the North Denmark Region. METHODS: The study is a secondary analysis of data from a matched cohort study including 839 low-risk women intending birth in a freestanding midwifery unit (primary participants) and 839 low-risk women intending birth in an obstetric unit (individually matched control group). Analysis was by intention-to-treat. Conditional logistic regression analysis was applied to compute odds ratios and effect ratios with 95% confidence intervals for matched pairs stratified by parity. RESULTS: On no outcome did the effect of birthplace differ significantly between primiparous and multiparous women. Compared with their counterparts intending birth in an obstetric unit, both primiparous and multiparous women intending birth in a freestanding midwifery unit were significantly more likely to have an uncomplicated, spontaneous birth with good outcomes for mother and infant and less likely to require caesarean section, instrumental delivery, augmented labour or epidural analgesia (although for caesarean section this trend did not attain statistical significance for multiparous women). Perinatal outcomes were comparable between the two birth settings irrespective of parity. Compared to multiparas, transfer rates were substantially higher for primiparas, but fell over time while rates for multiparas remained stable. CONCLUSIONS: Freestanding midwifery units appear to confer significant advantages over obstetric units to both primiparous and multiparous mothers, while their infants are equally safe in both settings. Our findings thus support the provision of care in freestanding midwifery units as an alternative to care in obstetric units for all low-risk women regardless of parity. In view of the global rise in caesarean section rates, we consider it an important finding that freestanding midwifery units show potential for reducing first-birth caesarean.

Marker-dependent associations among oxidative stress, growth and survival during early life in a wild mammal.

Oxidative stress (OS) is hypothesized to be a key physiological mechanism mediating life-history trade-offs, but evidence from wild populations experiencing natural environmental variation is limited. We tested the hypotheses that increased early life growth rate increases OS, and that increased OS reduces first-winter survival, in wild Soay sheep (Ovis aries) lambs. We measured growth rate and first-winter survival for four consecutive cohorts, and measured two markers of oxidative damage (malondialdehyde (MDA), protein carbonyls (PC)) and two markers of antioxidant (AOX) protection (total AOX capacity (TAC), superoxide dismutase (SOD)) from blood samples. Faster lamb growth was weakly associated with increased MDA, but not associated with variation in the other three markers. Lambs with higher SOD activity were more likely to survive their first winter, as were male but not female lambs with lower PC concentrations. Survival did not vary with MDA or total TAC. Key predictions relating OS to growth and survival were therefore supported in some OS markers, but not others. This suggests that different markers capture different aspects of the complex relationships between individual oxidative state, physiology and fitness, and that overarching hypotheses relating OS to life-history variation cannot be supported or refuted by studying individual markers.

The insulinotropic effect of exogenous glucagon-like peptide-1 is not affected by acute vagotomy in anaesthetized pigs.

What is the central question of this study? We investigated whether intestinal vagal afferents are necessary for the insulinotropic effect of glucagon-like peptide-1 (GLP-1) infused into a mesenteric artery or a peripheral vein before and after acute truncal vagotomy. What is the main finding and its importance? We found no effect of truncal vagotomy on the insulinotropic effect of exogenous GLP-1 and speculate that high circulating concentrations of GLP-1 after i.v. and i.a. infusion might have overshadowed any neural signalling component. We propose that further investigations into the possible vagal afferent signalling of GLP-1 would best be pursued using enteral stimuli to provide high subepithelial levels of endogenous GLP-1. Glucagon-like peptide 1 (GLP-1) is secreted from the gut in response to luminal stimuli and stimulates insulin secretion in a glucose-dependent manner. As a result of rapid enzymatic degradation of GLP-1 by dipeptidyl peptidase-4, a signalling pathway involving activation of intestinal vagal afferents has been proposed. We conducted two series of experiments in α-chloralose-anaesthetized pigs. In protocol I, pigs (n = 14) were allocated for either i.v. or i.a. (mesenteric) GLP-1 infusions (1 and 2 pmol kg(-1)  min(-1) , 30 min) while maintaining permissive glucose concentrations at 6 mmol l(-1) by i.v. glucose infusion. The GLP-1 infusions were repeated after acute truncal vagotomy. In protocol II, pigs (n = 27) were allocated into six groups. Glucagon-like peptide 1 was infused i.v. or i.a. (mesenteric) for 1 h at 3 or 30 pmol kg(-1)  min(-1) . During the steady state (21 min into the GLP-1 infusion), glucose (0.2 g kg(-1) , i.v.) was administered over 9 min to stimulate ß-cell secretion. Thirty minutes after the glucose infusion, GLP-1 infusions were discontinued. Following a washout period, the vagal trunks were severed in four of six groups (vagal trunks were left intact in two of six groups), whereupon all infusions were repeated. We found no effect of vagotomy on insulin or glucagon secretion during administration of exogenous GLP-1 in any experiment. We speculate that the effect of exogenous GLP-1 overshadowed any effect occurring via the vagus. Within dosage groups, total GLP-1 concentrations were similar, but intact GLP-1 concentrations were much lower when infused via the mesenteric artery because of extensive degradation of GLP-1 in the splanchnic bed. This demonstrates the effectiveness with which intestinal capillary dipeptidyl peptidase-4 protects the systemic circulation from intact GLP-1, consistent with a local role for GLP-1 involving activation of vagal pathways.

Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition.

PURPOSE: We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. METHODS: Double-blinded, placebo-controlled study in 54 men aged 60-78 years with bioavailable testosterone < 7.3 nmol/L and waist > 94 cm randomized to TT (gel, 50-100 mg/day, n = 20), placebo (n = 18) or ST (n = 16) for 6 months. Moreover, the ST group was randomized to TT (ST + TT, n = 7) or placebo (ST + placebo, n = 9) after 3 months. OUTCOMES: sCD36, total and regional fat mass were established by Dual X-ray absorptiometry and magnetic resonance imaging. Data are presented as median (quartiles). Kruskal-Wallis and Mann-Whitney tests were performed on delta values at 0, 3 and 6 months. RESULTS: ST + placebo decreased sCD36 levels by 21% [from 0.80 (0.68-1.22) to 0.63 (0.51-0.73) rel. units] vs. TT and vs. placebo (p < 0.05). ST + placebo did not change bioavailable testosterone and lean body mass. Fat mass measures significantly improved during ST + placebo, ST + TT, and TT vs. placebo. During ST + placebo, delta sCD36 was associated with delta total fat mass (r = 0.81) and delta central fat mass (r = 0.84). CONCLUSIONS: Compared to testosterone treatment, six months of strength training reduced sCD36 levels suggesting decreased cardiovascular risk, possibly due to a reduction in central fat mass.

Whole-body oxidative stress reduction during testosterone therapy in aging men: A randomized placebo-controlled trial.

BACKGROUND: Testosterone replacement therapy in aging men increases lean body mass and decreases whole-body fat. The safety of testosterone replacement therapy concerning cardiovascular disease is unresolved and assessment of whole-body oxidative stress may contribute to future decision making. OBJECTIVES: To determine whole-body oxidative stress during testosterone replacement therapy and placebo in aging men and evaluate if a change in oxidative stress was mediated by changed body composition. MATERIALS AND METHODS: This was a double-blinded, randomized, placebo-controlled study for 24 weeks in 38 men aged 60-78 years with bioavailable testosterone <7.3 nmol/L and waist circumference ≥94 cm who were randomized to testosterone replacement therapy (testosterone gel) (N = 20) or placebo (N = 18). At baseline and after 24 weeks, whole-body oxidative stress was assessed by oxidized derivatives of nucleic acids, 8-oxoguanosine and 8-oxo-2'-deoxyguanosine in 24-h urine samples by ultra-performance liquid chromatography tandem mass spectrometry. Lean body mass and whole-body fat were measured by dual X-ray absorptiometry. Subcutaneous and visceral adipose tissue were estimated by magnetic resonance imaging. Testosterone replacement therapy versus placebo was compared by Mann-Whitney tests on ∆-values (24-0 weeks). RESULTS: Baseline age was 67 (64-72) years (median [interquartile range]), body mass index 29.8 (26.6-33.3) kg/m2 , waist 107 (99-117) cm, and bioavailable testosterone 4.7 (3.7-5.9) nmol/L. During testosterone replacement therapy, 8-oxoguanosine in 24-h urine samples decreased from 21.6 (19.8; 27.7) nm to 15.0 (12.2; 18.8) nm (p = 0.038 vs. placebo), lean body mass increased (p < 0.01) and whole-body fat (p = 0.02) and subcutaneous adipose tissue (p < 0.01) decreased. 8-Oxoguanosine in 24-h urine samples was inversely associated with Δ-lean body mass (ρ = -0.38, p = 0.03), which remained significant after adjusting for Δ-total testosterone. 8-Oxo-2'-deoxyguanosine in 24-h urine samples was unchanged (p = 0.06) during testosterone replacement therapy and Δ-8-oxo-2'-deoxyguanosine in 24-h urine samples was associated with Δ-whole-body fat (kg) (ρ = 0.47, p < 0.01). Δ-Values of oxidative stress biomarkers were not associated with Δ-fasting insulin or Δ-homeostatic model assessment of insulin resistance. DISCUSSION: Oxidative stress decreased during testosterone replacement therapy compared to placebo, which could be mediated by changed body composition. CONCLUSION: Whole-body oxidative stress decreased during 24 weeks of testosterone replacement therapy in aging men.

A characterization of patients with low soluble urokinase plasminogen activator receptor who died within 90 days of hospital discharge.

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry-based study. Compared to patients with low suPAR who survived (n = 15 122), those who died within 90 days (n = 87) had higher age (75.4 years), higher medication use (7.0; 71.3% with polypharmacy) and more blood tests outside reference intervals (5.0) (including C-reactive protein, neutrophils and albumin), and the most common diagnoses were chronic pulmonary disease (27.6%), cerebrovascular disease (18.4%) and dementia (11.5%). Patients with low suPAR were more morbid than what was reflected by suPAR alone. Future studies must determine which factors that contribute the most to potential algorithms when stratifying patients based on their risk of adverse clinical outcomes. These data indicate that inclusion of medication data could be relevant.

Impact of androgenic anabolic steroid use on cardiovascular and mental health in Danish recreational athletes: protocol for a nationwide cross-sectional cohort study as a part of the Fitness Doping in Denmark (FIDO-DK) study.

INTRODUCTION: The use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational studies. This large-scale study aims to investigate the impact of AAS use on vascular plaque formation, preclinical coronary disease, cardiac function, circulating cardiovascular risk markers, quality of life (QoL) and mental health in a broad population of illicit AAS users. METHODS AND ANALYSES: A nationwide cross-sectional cohort study including a diverse population of men and women aged ≥18 years, with current or previous illicit AAS use for at least 3 months. Conducted at Odense University Hospital, Denmark, the study comprises two parts. In part A (the pilot study), 120 recreational athletes with an AAS history will be compared with a sex-matched and age-matched control population of 60 recreational athletes with no previous AAS use. Cardiovascular outcomes include examination of non-calcified coronary plaque volume and calcium score using coronary CT angiography, myocardial structure and function via echocardiography, and assessing carotid and femoral artery plaques using ultrasonography. Retinal microvascular status is evaluated through fundus photography. Cardiovascular risk markers are measured in blood. Mental health outcomes include health-related QoL, interpersonal difficulties, body image concerns, aggression dimensions, anxiety symptoms, depressive severity and cognitive function assessed through validated questionnaires. The findings of our comprehensive study will be used to compose a less intensive investigatory cohort study of cardiovascular and mental health (part B) involving a larger group of recreational athletes with a history of illicit AAS use. ETHICS AND DISSEMINATION: The study received approval from the Regional Committee on Health Research Ethics for Southern Denmark (S-20210078) and the Danish Data Protection Agency (21/28259). All participants will provide signed informed consent. Research outcomes will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT05178537.