The study showed that compared to pre-menopausal women, post-menopausal women have a:1
- 13% increased risk of metabolic syndrome (MetS)
- 28% increased risk of hypertension
- 7% increased risk of elevated triglycerides
- 71% increased risk of elevated plasma glucose
- 95% risk of higher waist-to-hip ratios.
The above-mentioned are all well-known risk factors for cardiovascular diseases (CVD). Women >40-years are at greatest risk of ischaemic heart disease (IHD). This may be due to changes in hormone levels associated with menopause, and the accumulation of body fat, such as abdominal obesity due to ageing.2
Post-menopausal women also show a greater increases in systolic blood pressure (BP), and total cholesterol and triglyceride levels, as well as low density lipoprotein (LDL) associated with the development of CVD.2
Mortality and morbidity associated with IHD among post-menopausal women is higher than that of men in the same age group.2
According to the authors of the new study, their findings underscore the urgent need for public health policies that focus on early monitoring and interventions targeted at reducing CMD risk and related adverse outcomes in menopausal women in LMICs.1
As a result of their increased risk of CMD, post-menopausal women may develop insulin resistance, type 2 diabetes (T2DM), non-alcoholic fatty liver disease/metabolic associated fatty liver disease.3
Influence of lifestyle and environmental factors on the risk of CMD
Regional variations in the risk of CMD highlight the influence of lifestyle and environmental factors. In an earlier study, Chikwati et al compared the risk factors for CMD between women from four sub-Saharan African countries (Ghana, Burkina Faso, Kenya, and South Africa). A total of 3 609 women (1 740 pre-menopausal and 1 869 post-menopausal) were recruited.4
The prevalence rates of risk factors for CMD were higher in South and East Africa, irrespective of menopausal stage. A lower risk was observed in women from West Africa, which may be due to differences in environmental and/or lifestyle related factors, postulate the authors.4
West African populations are predominantly subsistence farmers whereas women recruited from the East and South African sites were more urbanised.4
In addition, the West African study participants had a lower dietary intake of bread, soft drinks and fruit than observed at the other study sites and obesity was far less prevalent in the West African population.4
Another interesting finding from this study is that no differences were observed in waist circumference, subcutaneous fat, diastolic and systolic BP, carotid intima media thickness, LDL-cholesterol and triglyceride levels between pre- and post-menopausal South and East African women.4
Decline of metabolic health during menopause
As mentioned, CMD increases the risk of CVD post-menopause. CVD risks associated with menopause have been documented since the mid-1970s when Framingham investigators noted a 2.6-fold increase in CV events in age-matched post-menopausal women compared to pre-menopausal women.3
This trend persisted across subsequent observational studies. The hypothesis is that the heightened risk in older women results from the mid-life decline in endogenous sex steroids during the menopausal transition.3
Several observations support this hypothesis. Menopause is linked to a more atherogenic lipid profile, with increased total cholesterol, triglycerides, and LDL-cholesterol, along with reduced high-density lipoprotein- (HDL) cholesterol.3
According to the North American Menopause Society (NAMS), the menopause transition is associated with changes in body composition, including increased body fat, decreased lean body mass, and altered fat-to-lean ratio.5
On average, women experience a yearly weight gain of 0.6kg during the menopause transition period, with a shift in central fat distribution. This pattern, known as gynoid-to-android, is observed around two years after the final menstrual period, and weight changes tend to stabilise thereafter.5
Furthermore, menopause is linked to a higher percentage of epicardial and paracardial adipose tissue, which are risk factors for IHD. Oestrogen, the hormone affected by menopause, plays a role in systemic factors regulation, influencing serum lipids, coagulation systems, antioxidant systems, and vasoactive molecules.3
Oestrogen acts through both genomic and non-genomic pathways, the former regulating gene transcription, and the latter facilitating rapid effects like arterial vasodilation.3
Oestrogen's vascular effects vary based on atherosclerosis presence. Its anti-atherosclerotic impact may diminish in diseased arteries due to reduced oestrogen receptor expression. Studies suggest that the anti-atherosclerotic effects of oestrogen are more apparent when minimal underlying atherosclerosis is present.3
Managing metabolic disorders to prevent CVD
Managing metabolic disorders in menopausal women involves a multifaceted approach, which includes pharmacotherapy, and lifestyle modifications.6
Pharmacotherapy is aimed at addressing hypertension, dyslipidaemia, and abnormalities in glucose metabolism, including T2DM. BP goals involve maintaining levels <120/80mmHg, with pharmacotherapy recommended if values >140/90mmHg.3
Lipid targets include LDL-cholesterol <2.5mmol/l, HDL-cholesterol >1.2mmol/l, triglycerides <1.6mmol/l, and non-HDL-cholesterol <3.3mmol/l, with pharmacotherapy recommended to achieve these goals.3
Lifestyle modifications, including physical activity (regular moderate exercise ) and a calorie-controlled diet, play a pivotal role. Healthy diets, incorporating seafood, seaweeds, grains, dairy products, vegetables, and fruits, are associated with reduced risk of CVD.3
Smoking cessation, limited alcohol consumption, as well as maintaining a BMI <25 or waist size <88cm are also recommended. Additionally, nutrition and supplementation with vitamin D, omega-3 fatty acids, antioxidants, phytochemicals, and probiotics are recommended, although further research is needed to establish their efficacy.3,5
Consideration when initiating hormone therapy
According to a Women's Health Initiative (WHI) study, hormone therapy - specifically continuous-combined conjugated equine oestrogen (CEO) plus medroxyprogesterone acetate (MPA) - has shown a significant 19% reduction in the incidence of T2DM in women. The reduction in new diagnoses of T2DM was 14% for CEO alone.5
Additionally, a meta-analysis indicated that oestrogen-progestogen therapy (OPT) resulted in a 30% decrease in T2DM incidence. Another meta-analysis confirmed these findings and reported better glycaemic control in women with T2DM using oestrogen therapy or OPT. However, it should be noted that the benefits reverse upon discontinuation.5
OPT has demonstrated no significant impact on weight or, in some cases, is associated with less weight gain compared to women not using therapy. A WHI study showed that women using CEE with or without MPA did not show a statistically significant difference in weight gain or waist circumference increase over the initial three years of therapy compared to those receiving a placebo.5
Can hormone therapy prevent CVD?
Hormone therapy is not indicated as primary or secondary prevention of CVD. Patient characteristics, initiation timing, and types are critical factors influencing hormone therapy’s preventive effect on CVD events.3,5
CVD risk assessment is vital for women considering hormone therapy. Women with a high risk of CVD include those with a family history of premature atherosclerotic CVD (ASCVD), hypercholesterolaemia, MetS, chronic kidney disease, chronic inflammatory conditions, premature menopause, pregnancy-related conditions (eg pre-eclampsia), high-risk race/ethnicity, persistently elevated triglycerides, high lipoprotein, high apolipoprotein B, and ankle-brachial index <0.9.3
Women with high-risk scores are not suitable candidates for hormone therapy, while low-risk individuals may be suitable.3
According to NAMS, observational data and reanalysis of older studies, including WHI studies, suggest that for healthy women within 10 years of menopause onset, the benefits of hormone therapy outweigh its risks, especially in reducing CVD events in younger versus older women.5
Initiation of hormone therapy within this timeframe shows favourable effects on surrogate markers of coronary heart disease (CHD) and clinical outcomes.5
Studies focusing on women within 10 years of menopause onset indicate potential benefits in reducing atherosclerosis progression measured by coronary artery calcification and subclinical ASCVD.5
The Early Versus Late Intervention Trial With Estradiol demonstrated a reduction in subclinical ASCVD progression when hormone therapy was initiated within six years of menopause onset but not when started ≥10-years afterward.5
Meta-analyses of trial data support the idea that hormone therapy initiated within 10 years of menopause onset lowers the risk of CHD and all-cause mortality while showing no increased risk of stroke but an elevated risk of venous thromboembolism (VTE).5
During the intervention phase, CHD, myocardial infarction (MI), and coronary procedures showed a lowered hazard ratio in women aged <60-years and within 10 years of menopause onset. Subsequent cumulative follow-up studies also demonstrated significant age-treatment interactions, indicating a reduction in MI risk and all-cause mortality in the 50- to 59-year-old age group.5
For women initiating hormone therapy >10-years from menopause onset or aged >60-years, meta-analyses consistently show no evidence of a beneficial effect on CHD or all-cause mortality, with an increased risk of stroke and VTE.5
Stroke risk attributable to hormone therapy in women aged <60-years or within 10 years of menopause onset is rare and statistically non-significant for some formulations, such as CEO plus MPA, while findings for CEO alone are inconsistent.5
Observational studies suggest lower doses of oral or transdermal oestrogen may confer less risk of stroke, but no clear association with age has been established. VTE risk is elevated in women who initiated hormone therapy aged >60-years or >10-years since menopause but not in those aged <60- years or within 10 years of menopause. Comparative data on different formulations and routes of delivery are limited.5
Conclusion
Studies emphasise the significant impact of menopause on increasing susceptibility to CMDs. The identified risks include MetS, hypertension, elevated triglycerides, and glucose levels - all established precursors to CVD. Regional variations in CMD risk underscore the influence of lifestyle and environmental factors.
The prevention of CVDs in post-menopausal women involves a comprehensive approach, incorporating pharmacotherapy, and lifestyle modifications.
While hormone therapy is not recommended as primary or secondary prevention for CVD, observational and re-analysed studies, particularly focusing on initiation within 10 years of menopause onset, suggest potential benefits in reducing CVD events.
Further research is crucial to address these uncertainties and establish the role of hormone therapy in preventing CVD in post-menopausal women, particularly in diverse populations.
REFERENCES
- Chikwati RP, Chikowore T, Mahyoodeen, et al. The association of menopause with cardiometabolic disease risk factors in low- and middle-income countries: a systematic review and meta-analyses. Menopause, 2024.
- Ra JS, Kim HS, Jeong YH. Associated Factors of Ischemic Heart Disease Identified Among Post-Menopausal Women. Osong Public Health Res Perspect, 2019.
- Prabakaran S, Schwartz A, Lundberg G. Cardiovascular risk in menopausal women and our evolving understanding of menopausal hormone therapy: risks, benefits, and current guidelines for use. Ther Adv Endocrinol Metab, 2021.
- Chikwati RP, Mayoodeen NG, Jaff NG, et al. Cardiometabolic disease risk factors in pre- and postmenopausal women from four sub-Saharan African countries: A cross-sectional study. Maturitas, 2023.
- Faubion SS, Crandall CJ, Davis L, et al. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause, 2022.
- Jeong HG, Park H. Metabolic Disorders in Menopause. Metabolites, 2022.
