Females and males are known to have different abilities to cope with stress and disease. This study was designed to investigate the effect of sex on properties of a complex interlinked network constructed of central biochemical metabolites. The study involved the blood collection and analysis of a large set of blood metabolic markers from a total of 236 healthy participants, which included 140 females and 96 males. Metabolic profiling yielded concentrations of 168 metabolites for each subject. A differential correlation network analysis approach was developed for this study that allowed detection and characterization of interconnection differences in metabolites in males and females. Through topological analysis of the differential network that depicted metabolite differences in the sexes, we identified metabolites with high centralities in this network. These key metabolites were identified as 10 phosphatidylcholines (PCaaC34:4, PCaaC36:6, PCaaC34:3, PCaaC42:2, PCaeC38:1, PCaeC38:2, PCaaC40:1, PCaeC34:1, PC aa C32:1 and PC aa C40:6) and 4 acylcarnitines (C3-OH, C7-DC, C3 and C0). Identification of these metabolites may help further studies of sex-specific differences in the metabolome that may underlie different responses to stress and disease in males and females.

Menopause is an endocrine-related transition that induces a number of physiological and potentially pathological changes in middle-aged and elderly women. The intention of this research was to investigate the influence of menopause on the intricate relationships between major biochemical metabolites. The study involved metabolic profiling of 186 metabolic markers measured in blood plasma collected from 120 healthy female participants. We developed a method of network analysis using differential correlation that enabled us to detect and characterize differences in metabolites and changes in inter-relationships in pre- and post-menopausal women. A topological analysis was performed on the differential network that uncovered metabolite differences in pre-and post-menopausal women. In this analysis, our method identified two key metabolites, sphingomyelins and phosphatidylcholines, which may be useful in directing further studies into menopause-specific differences in the metabolome, and how these differences may underlie the body's response to stress and disease following the transition from pre- to post-menopausal status for women.