Professional athletes undertake a variety of training programs to enhance their physical performance, technical-tactical skills, while protecting their health and well-being. Regular exercise induces widespread changes in the whole body in an extremely complex network of signaling, and evidence indicates that phenotypical sex differences influence the physiological adaptations to player load of professional athletes. Despite that there remains an underrepresentation of women in clinical studies in sports, including football. The objectives of this study were twofold: to study the association between the external load (EPTS) and urinary metabolites as a surrogate of the adaptation to training, and to assess the effect of sex on the physiological adaptations to player load in professional football players. Targeted metabolic analysis of aminoacids, and tryptophan and phenylalanine metabolites detected progressive changes in the urinary metabolome associated with the external training load in men and women’s football teams. Overrepresentation analysis and multivariate analysis of metabolic data showed significant differences of the effect of training on the metabolic profiles in the men and women teams analyzed. Collectively, our results demonstrate that the development of metabolic models of adaptation in professional football players can benefit from the separate analysis of women and men teams, providing more accurate insights into how adaptation to the external load is related to changes in the metabolic phenotypes. Furthermore, results support the use of metabolomics to understand changes in specific metabolic pathways provoked by the training process.

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Background: Single-nucleotide polymorphisms (SNPs) in collagen genes are predisposing factors for anterior cruciate ligament (ACL) rupture. Although these events are more frequent in females, the sex-specific risk of reported SNPs has not been evaluated. Purpose: We aimed to assess the sex-specific risk of historic non-contact ACL rupture considering candidate SNPs in genes previously associated with muscle, tendon, ligament and ACL injury in elite footballers. Study Design: This was a cohort genetic association study. Methods: Forty-six (twenty-four females) footballers playing for the first team of FC Barcelona (Spain) during the 2020–21 season were included in the study. We evaluated the association between a history of non-contact ACL rupture before July 2022 and 108 selected SNPs, stratified by sex. SNPs with nominally significant associations in one sex were then tested for their interactions with sex on ACL. Results: Seven female (29%) and one male (4%) participants had experienced non-contact ACL rupture during their professional football career before the last date of observation. We found a significant association between the rs13946 C/C genotype and ACL injury in women footballers (p = 0.017). No significant associations were found in male footballers. The interaction between rs13946 and sex was significant (p = 0.027). We found that the C-allele of rs13946 was exclusive to one haplotype of five SNPs spanning COL5A1. Conclusions: The present study suggests the role of SNPs in genes encoding for collagens as female risk factors for ACL injury in football players. Clinical Relevance: The genetic profiling of athletes at high risk of ACL rupture can contribute to sex-specific strategies for injury prevention in footballers.