The Women4Health cohort: a unique cohort to study women-specific mechanisms of cardio-metabolic regulation

Abstract

Aims: Epidemiological research has shown relevant differences between sexes in clinical manifestations, severity, and progression of cardiovascular and metabolic disorders. To date, the mechanisms underlying these differences remain unknown. Given the rising incidence of such diseases, gender-specific research on established and emerging risk factors, such as dysfunction of glycaemic and/or lipid metabolism, of sex hormones and of gut microbiome, is of paramount importance. The relationships between sex hormones, gut microbiome, and host glycaemic and/or lipid metabolism are largely unknown even in the homoeostasis status. Yet this knowledge gap would be pivotal to pinpoint to key mechanisms that are likely to be disrupted in disease context.

Methods and results: Here we present the Women4Health (W4H) cohort, a unique cohort comprising up to 300 healthy women followed up during a natural menstrual cycle, set up with the primary goal to investigate the combined role of sex hormones and gut microbiota variations in regulating host lipid and glucose metabolism during homoeostasis, using a multi-omics strategy. Additionally, the W4H cohort will take into consideration another ecosystem that is unique to women, the vaginal microbiome, investigating its interaction with gut microbiome and exploring-for the first time-its role in cardiometabolic disorders.

Conclusion: The W4H cohort study lays a foundation for improving current knowledge of women-specific mechanisms in cardiometabolic regulation. It aspires to transform insights on host-microbiota interactions into prevention and therapeutic approaches for personalized health care.

Keywords: Cardiovascular diseases; Lipids; Microbiome; Multi-omics study; Sex hormones; Women.

Figure 1

Scheme of the study design. Schematic representation of study design, showing data collection, study period, and enrolment criteria. The arrow in the first panel points to phenotypes considered as outcomes. The figure was designed using infographics downloaded from Freepik.com.

Figure 2

Variation of sex hormones by week of collection. Box plots describing the distribution of sex hormones at each time point. In each box plot, the tick line represents the median while the edges of the box represent the 25% and 75% of the distribution; whiskers represent 5% and 95% percentiles. For each trait, P-values of both the Friedman test for overall differences and the Wilcoxon test for pairwise differences are reported. 17BE, 17beta-oestradiol (pg/mL); PROG, progesterone (ng/mL); LH, luteinizing hormone (mIU/mL); FSH, follicular-stimulating hormone (mIU/mL); PRL, prolactin (ng/mL).