Women’s cardiovascular health - what about menopause and atherosclerotic cardiovascular disease?

Women will undergo menopause usually between 48 and 52 years of age. Menopause is characterised by a decrease in 17β-oestradiol (E2) and an increase in follicle-stimulating hormone (FSH). This hormonal shift during menopause is believed to increase the risk for atherosclerotic cardiovascular disease (ACVD) in women. However, establishing a causal relationship between menopause-driven metabolic changes and subsequent ACVD is complicated. For one, the timing of menopause is different for every woman. Further, menopause is also associated with an increase in body fat percentage which is also a well-known risk factor for ACVD.

An elegant recent study by Karpinnen et al. (1) circumvented some of these challenges by employing a longitudinal study design. The authors used data from the Estrogenic Regulation of Muscle Apoptosis (ERMA) prospective cohort study to assess the association between menopause status and circulating metabolites. For their analysis, linear mixed-effects models with random intercept were employed with menopausal status as exposure and metabolite concentration as outcome. A total of 183 women were included in the main analysis. All of these women had experienced natural menopause. In addition to their main analysis, two exploratory approaches were used to determine the direct and indirect effects of the menopausal hormonal shift and metabolite changes as well as the effect of oestrogen-containing menopausal hormone therapy. Interestingly, the menopause-induced hormonal shift was associated with a proatherogenic metabolic fingerprint (e.g. higher levels of very low density lipoprotein and low density lipoprotein). These results were independent of body fat percentage and consistent with findings in women who use menopausal hormone therapy. Using a sensitivity analysis the authors further showed that the reduction in E2 was more important for the observed associations compared the increase in FSH. Overall, these findings highlight the importance of menopause with regards to women’s cardiovascular health.