Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males, whereas evidence for affected autistic girls is sparse. Therefore, a comprehensive gas chromatography mass spectrometry-based steroid hormone metabolite analysis was conducted from autistic girls. Results show increased levels of several steroid hormones, especially in the class of androgens in autistic girls such as testosterone or androstenediol. The increase of the majority of steroid hormones in autistic girls is probably best explained multifactorially by a higher substrate provision in line with the previously developed cholesterol hypothesis of autism.

Objectives: It is common nowadays to refer to autism as a spectrum. Increased evidence of the involvement of steroid metabolites has been shown by the presence of stronger alterations in Kanner’s syndrome compared with Asperger syndrome. Methods: 24 h urine samples were collected from 20 boys with Asperger syndrome, 21 boys with Kanner’s syndrome, and identically sized control groups, each matched for age, weight, and height for comprehensive steroid hormone metabolite analysis via gas chromatography–mass spectrometry. Results: Higher levels of most steroid metabolites were detected in boys with Kanner’s syndrome and Asperger syndrome compared to their matched controls. These differences were more pronounced in affected individuals with Kanner’s syndrome versus Asperger syndrome. Furthermore, a specific and unique pattern of alteration of androsterone, etiocholanolone, progesterone, tetrahydrocortisone, and tetrahydrocortisol was identified in boys with Kanner’s syndrome and Asperger syndrome. Interestingly, in both matched samples, only androsterone, etiocholanolone, progesterone, tetrahydrocortisone, tetrahydrocortisol, and 5a-tetrahydrocortisol groups were positively correlated. In the Asperger syndrome group, all metabolites showed a positive correlation. In the Kanner’s syndrome group, 5-a tetrahydrocortisol with androsterone showed a positive correlation. Conclusions: Due to differences in the level of alteration, the premise that Asperger syndrome is on the mild side of the autism spectrum and that Kanner’s syndrome is on the severe side is supported, but alteration patterns yield different phenotypic expressions.

Various disturbances of social behavior, such as autism, depression, or posttraumatic stress disorder, have been associated with an altered steroid hormone homeostasis and a dysregulation of the hypothalamus–pituitary–adrenal axis. A link between steroid hormone antagonists and the treatment of stress-related conditions has been suggested. We evaluated the effects of stress induction on social behavior in the three chambers and its potential reversibility upon specific steroid hormone antagonism in mice. C57BL/6 mice were stressed twice daily for 8 days by chronic swim testing. Social behavior was evaluated by measuring, first, the preference for sociability and, second, the preference for social novelty in the three-chamber approach before and after the chronic swim test. The reversibility of behavior upon stress induction was analyzed after applying steroid hormone antagonists targeting glucocorticoids with etomidate, mineralocorticoids with potassium canrenoate, and androgens with cyproterone acetate and metformin. In the chronic swim test, increased floating time from 0.8 ± 0.2 min up to 4.8 ± 0.25 min was detected (p < 0.01). In the three-chamber approach, increased preference for sociability and decreased preference for social novelty was detected pre- versus post-stress induction. These alterations of social behavior were barely affected by etomidate and potassium canrenoate, whereas the two androgen antagonists metformin and cyproterone acetate restored social behavior even beyond baseline conditions. The alteration of social behavior was better reversed by the androgen as compared with the glucocorticoid and mineralocorticoid antagonists. This suggests that social behavior is primarily controlled by androgen rather than by glucocorticoid or mineralocorticoid action. The stress-induced changes in preference for sociability are incompletely explained by steroid hormone action alone. As the best response was related to metformin, an effect via glucose levels might confound the results and should be subject to future research.

Introduction: There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher production of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione/androstenediol seems especially present in autism. Methods: An encompassing literature analysis was performed, searching for altered androgens in children with autism and using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Included were all studies published before 31 March 2021 found using the following electronic databases: PubMed, Google Scholar, Cochrane Library, Scopus, and TRIP. Eight studies with boys and three studies with girls where steroid hormone measurements were performed from either plasma, urine, or saliva were found and analyzed. Analyses were performed for DHEA(-S/-C), androstenedione/androstenediol, and testosterone. Effect sizes were calculated for each parameter between mean concentrations for children with autism versus healthy controls. Results: Higher levels of androgens in autism were detected, with the majority of calculated effect sizes being larger than one. Conclusions: We found higher levels of the main testosterone precursors DHEA, androstenedione, and androstenediol, likely causing an additionally higher level of testosterone, and an increased 17, 20-lyase activity is therefore implied. Medications already used in PCOS such as metformin might be considered to treat hyperandrogenism in autism following further research.

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BackgroundThe efficiency of aerobic energy provision to working skeletal muscle is affected by aerobic fitness and a prominent insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE-I/D) gene for the major modulator of tissue perfusion. We assessed whether variability in the fitness state is dependent on the contribution of multiple aspects of oxygen transport to the development of muscle power, and the respective control coefficients, are associated with the ACE-I/D genotype.MethodsTwenty-five women and 19 men completed a ramp test of cycling exercise to exhaustion during which serial steps of oxygen transport [oxygen uptake (L O2 min−1) (VO2), minute ventilation in (L min−1) (VE), cardiac output in equivalents of L min−1 (Q), arterial oxygen saturation (SpO2), muscle oxygen saturation (SmO2), and total hemoglobin concentration (g dL−1) (THb) in Musculus vastus lateralis and Musculus gastrocnemius, respiration exchange ratio (RER)], blood lactate and glucose concentration, were continuously monitored. The contribution/reliance of power output (PO) on the parameters of oxygen transport was estimated based on the slopes in Pearson's moment correlations (|r| &gt; 0.65, p &lt; 0.05) vs. power values over the work phase of the ramp test, and for respective fractional changes per time (defining control coefficients) over the rest, work, and recovery phase of the ramp test. Associations of variability in slopes and control coefficients with the genotype and aerobic fitness were evaluated with ANOVA.ResultsAll parameters characterizing aspects of the pathway of oxygen, except THb, presented strong linear relationships [(|r| &gt; 0.70) to PO]. Metabolic efficiency was 30% higher in the aerobically fit subjects [peak oxygen uptake (mL O2 min−1) (VO2peak) ≥ 50 ml min−1 kg−1], and energy expenditure at rest was associated with the fitness state × ACE-I/D genotype, being highest in the fit non-carriers of the ACE D-allele. For VO2, VE, and RER the power-related slopes of linear relationships during work demonstrated an association with aerobic fitness, being 30–40% steeper in the aerobically fit than unfit subjects. For VE the power-related slope also demonstrated an association with the ACE-I/D genotype. For increasing deficit in muscle oxygen saturation (DSmO2) in Musculus vastus lateralis (DSmO2 Vas), the power-related slope was associated with the interaction between aerobic fitness × ACE-I/D genotype.ConclusionLocal and systemic aspects of aerobic energy provision stand under influence of the fitness state and ACE-I/D genotype. This especially concerns the association with the index of the muscle's mitochondrial respiration (SmO2) which compares to the genetic influences of endurance training.

The aim of this study was to analyse if better orienteers run more constant yielding to suggest the better the place, the more constant the pace. In principle, this premise is supported from a biological point of view of the aerobe-anaerobic threshold concept, which is well elucidated in long distance running and implies that a constant pace slightly below the threshold leads to maximal performance through regularly use of cardiopulmonary and musculoskeletal system. To test this assumption race times of orienteers from the world championships at the Swedish Westcoast in Strömstad / Tanum were analysed concerning their steadiness of speed during the final course of middle and long-distance races. Interestingly statistical analyses mainly support the premise of relevance of steadiness in running. In woman, for long/middle distance a coefficient of determination between time and steadiness (calculated as standard deviation of all percentage deviations of individual split times and best time) of R 2 = 0.254 respectively of R 2 = 0.825 was detected. In men, for long/middle distance of R 2 = 0.176 respectively of R 2 = 0.472. Although, the method does not allow to strictly distinguish between cognitive and biological factors, it is implied that world class orienteers or more general orienteers get best results if running as constant as possible probably slightly below anaerobic threshold.

Background: Skiing is a popular outdoor sport posing different requirements on musculoskeletal and cardiorespiratory function to excel in competition. The extent to which genotypic features contribute to the development of performance with years of ski-specific training remains to be elucidated. We therefore tested whether prominent polymorphisms in genes for angiotensin converting enzyme (ACE-I/D, rs1799752), tenascin-C (TNC, rs2104772), actinin-3 (ACTN3, rs1815739) and PTK2 (rs7460 and rs7843014) are associated with the differentiation of cellular hallmarks of muscle metabolism and contraction in high level skiers. Material & Methods: Forty-three skiers of a world-leading national ski team performed exhaustive cardiopulmonary exercise testing as well as isokinetic strength testing for single contractions, whereby 230 cardiopulmonary measurements were performed in the period from 2015–2018. A total of 168 and 62 data measurements were from the Alpine and Nordic skiing squads, respectively. Ninety-five and one hundred thirty-five measurements, respectively, were from male and female athletes. The average (± SD) age was 21.5 ± 3.0 years, height 174.0 ± 8.7 cm, and weight 71.0 ± 10.9 kg for the analysed skiers. Furthermore, all skiers were analysed concerning their genotype ACE-I/D, Tenascin C, ACTN3, PTK2. Results: The genotype distribution deviated from Hardy–Weinberg equilibrium for the ACTN3 genotype, where rs1815739-TT genotypes (corresponding to the nonsense mutation) were overrepresented in world-class skiers, indicating a slow muscle fibre phenotype. Furthermore, the heterozygous rs2104772-AT genotypes of TNC also demonstrated the best scaled peak power output values during ramp exercise to exhaustion. The highest values under maximum performance for heart rate were associated with the rs1799752-II and rs1815739-CC genotypes. The lowest values for peak power of single contractions were achieved for rs1815739-CC, rs1799752-II and rs7843014-CT genotypes. The skiing discipline demonstrated a main influence on cardiorespiratory parameters but did not further interact with genotype-associated variability in performance. Discussion: Classically, it is pointed out that muscles of, for example, alpine skiers do not possess a distinct fibre type composition, but that skiers tend to have a preponderance of slow-twitch fibres. Consequently, our findings of an overrepresentation of ACTN3-TT genotypes in a highly selective sample of elite world class skiers support the potential superiority of a slow fibre type distribution. Conclusion: We suggest that one competitive advantage that results from a slow, typically fatigue-resistant fibre type distribution might be that performance during intense training days is better preserved, whereby simply a higher technical training volume can be performed, yielding to a competitive advantage.