Background Are the observed biological differences between men and women physiological, liked to sexual dimorphism, or can they be explained, at least in part, by social gender mechanisms ? We applied several methodological strategies to answer 4 questions: (1) Are there biological differences between men and women, and to what extent? (2) Do these differences vary when the early environment varies? (3) Are these differences explained, at least in part, by gender mechanisms? (4) Do these differences vary when socio-behavioral characteristics over the life course vary?

Methods We used two databases: the British birth cohort NCDS-58 and the French cohort CONSTANCES. We explored anthropometric measures; cardiovascular, metabolic, inflammatory, neuroendocrine biomarkers and an allostatic score. Three conceptualizations of gender were used: (a) gender as an individual characteristic, measured by a gender score defined using socio-behavioural characteristics; (b) gender as the effect of sex on socio-behavioural characteristics; and (c) gender as the interaction between sex and the social environment. For the analyses, we relied on the methodology of causal analyses, mediation analyses, and interaction analyses, based on conterfactual reasoning. We estimated the different effects using the g-computation method on bootstrapped and imputed data.

Results We observed that the levels of all biomarkers, except cortisol, were significantly different between women and men. Effect sizes of sex were larger than effect sizes of early social disadvantage, except for two inflammatory biomarkers. Biological measures were more unfavourable in men, except for lung function and most inflammatory biomarkers. Early social deprivation had a stronger effect in women for lipid levels, BMI, some inflammatory markers, and allostatic scores. We identified three types of gender mechanism to explain these Male-Female differences: (1) Mediation of the sex effect by gender mechanisms ; (2) Attenuation of the sex effect by gender mechanisms; and (3) Difference in sex effect according to early social environment and to socio-behavioral characteristics over the life course.

Conclusion The biological differences between men and women involve many biomarkers and are wider than those observed between other social groups. However, they are not purely explained by biological mechanisms and vary according to the social environment at the beginning and during life. These results open up new perspectives, both in terms of potential applications and in terms of methodology and understanding of gendered biological incorporation.