21/07/2025
Age-standardised rates of cardiovascular disease (CVD) are higher in men than women. The female rates are below the male rates at all ages, although the rates get closer with increasing age post menopause. CVD is a leading cause of death in women, worldwide, however this is under-recognised.
Menopause transition with reduction in s*x hormone levels is associated with certain metabolic changes such as central body fat accumulation, decreased energy expenditure, weight gain, insulin resistance and an altered lipid profile which can all have an adverse effect on blood vessel walls/atherosclerosis.
Women with premature ovarian insufficiency certainly have heightened CVD risk (lifestyle interventions and HRT at least until age of 51 recommended) and those with severe menopausal symptoms may have a more adverse cardiometabolic profile.
Eating healthy balanced diet with portion control, regular physical activity, weight management, quitting smoking/reducing alcohol consumption and treating high blood pressure/diabetes/abnormal lipid profile adequately - these are the main steps to prevent CVD. Hormone replacement therapy (HRT) when prescribed for treatment of menopausal symptoms or prevention of osteoporosis has a beneficial effect on cardiometabolic risk factors when started early within 10 years of onset of natural menopause in healthy women.
What are the other risk factors within the reproductive history that link up with raised CVD risk?
Here is an interesting paper from Bertomeu-Gonzalez et al. whose study aimed to assess the risk factors for incidence of major adverse cardiovascular events (MACE) exclusive to postmenopausal women.
It was a prospective cohort study in postmenopausal women 40 years and above.who were included in the UK Biobank cohort between 2006 and 2010 and followed to 2021 (12 years). A total of 156,787 women were followed for a median of 12.5 years and MACE risk was assessed using risk models.
The cumulative incidence of cardiovascular morbidity and mortality was 1.2% (0.97 cases per 1000 women-years). Postmenopausal women had significant, female-specific risks for cardiovascular morbidity and mortality. Findings suggested that not having taken contraceptive pills, nulliparity, and early menarche (≤12 years) were independently associated with cardiovascular morbidity and mortality. This association was independent of classic cardiovascular risk factors.
Data from both the literature and the present study clearly indicate that oestrogens protect women against cardiovascular disease. But above results also illustrate the complexity of this relationship with a higher risk found both in women who started menopause at younger ages and in women with early menarche suggesting that later the menstrual cycles start and end, the lower the risk will be.
The exogenous administration of oestrogens also showed paradoxical behaviour in this study with taking oral contraceptives reducing cardiovascular risk. We know that hormone replacement therapy could reduce cardiovascular risk when administered early in menopause, but this benefit appears to be lost if treatment is started 10 years later than onset. More evidence is needed to elucidate the complex relationship between pregnancies/live births and cardiovascular health as conflicting reports exist to the findings of this study.
Limitations of this study - the cohort might not adequately represent the general UK population and extrapolation of the results to populations in other countries warrants caution.
It is really important that we continue to do good quality research which is female specific to understand the complexities involved in hormone pathways and cardiovascular health in women.
Bertomeu-Gonzalez V, Cordero A, Ruiz-Nodar JM, Sánchez-Ferrer F, López-Pineda A, Quesada JA. Risk factors for major adverse cardiovascular events in postmenopausal women: UK Biobank prospective cohort study. Atherosclerosis. 2023 Dec;386:117372.
https://www.atherosclerosis-journal.com/article/S0021-9150(23)05293-0/fulltext
