From sex hormone decrease to hormonal treatment: impacts on cardiovascular risk with ageing

Ageing plays a critical role in the deterioration of artery function and structure, and clearly represents the first cardiovascular (CV) risk factor in men but also in women. Coronary and cerebral arteries are particularly prone to atheroma, and the tissues they perfuse are particularly vulnerable to ischaemia. In both sexes, the age-related decrease in sex hormones (menopause and andropause) has deleterious effects on CV health. The extent to which hormonal supplementation can limit the CV risks increased by ageing remains controversial. The Women Health Initiative study, the main clinical intervention designed to evaluate the benefit/risk ratio of hormone treatment after menopause, revealed in 2002 an unexpected increase in CV events in aged women (>70 years) given estrogens plus a peculiar synthetic progestin medroxyprogesterone acetate, whereas estrogens alone were not harmful but even protective in younger women (<60 years). This pointed out the double problem of the progestin (now natural progesterone is preferred) and of the age. The clinical situation is not yet clear for testosterone and CV disease in men. Related to these questions, we will analyse and summarize: (i) the importance of the doses and concentrations of estrogens and testosterone, both in humans and in experimental models, allowing to define relevant/physiological or pharmacological actions of sex hormones in respect to their medical modulations in practice; (ii) the main clinical studies conducted with estrogens or androgens, in terms of CV protection and the impact of age on these effects; (iii) the mechanisms underlying these actions; (iv) the gender-affirming hormone therapy, as these sex hormones are the cornerstone of gender transition care management.