Could exercise reduce the risk of cardiovascular disease for postmenopausal women?

The physiological changes women experience during and after the menopause can increase their risk of developing cardiovascular disease. The endothelium plays a significant role in this. In this Q&A with Lindsay Lew, Queen’s University, Canada, she discusses the impact of exercise on endothelial function and whether it is a beneficial intervention to maintain cardiovascular health as women age.

Lindsay Lew, Queen’s University, Canada

Firstly, what is the vascular endothelium?

The vascular endothelium is a single layer of cells that lines the inside of our blood vessels and these cells play an important role in regulating our cardiovascular health. Endothelial cells release an important molecule called nitric oxide that allows our blood vessels to widen, which is important for the delivery of oxygen to other tissues, like our muscles (1). Nitric oxide also helps protect our arteries against the development of atherosclerotic plaque (2).

What happens to the endothelium as we age? 

Endothelial function decreases as we age, primarily due to a decreased availability of nitric oxide (3, 4). As we age there is also an increase in oxidative stress, which is an increase in reactive oxygen species compared to antioxidants (5). This oxidative stress reduces nitric oxide bioavailability, contributing to endothelial dysfunction, which is when the blood vessels in our body cannot dilate as much (3, 4). Endothelial function is predictive of cardiovascular disease risk (6). Therefore, the decline in endothelial function with ageing means greater risk of developing atherosclerosis (the build up of fatty substances on the inner wall of the arteries) and cardiovascular disease.

Is the age-related decline the same for men and women?

Males experience a steady deterioration in endothelial function at an earlier age while females experience a steep decline in endothelial function at a later age (7, 8). This sudden decline in endothelial function coincides with the average age of menopause, which results in a deficiency in the primary female sex hormone, oestrogen. Oestrogen can protect the cardiovascular system as it can increase the production of nitric oxide (9).

Why is exercise training suggested as an intervention for postmenopausal women? How much research evidence supports this strategy?

Exercise is a well-established strategy to improve endothelial function and decrease cardiovascular disease risk in young adults and older men (10, 11). The increase in blood flow during exercise causes a frictional force against endothelial cells increasing the production of nitric oxide (12). In our review approximately two thirds of the 35 studies we examined showed that postmenopausal participants experienced a beneficial effect of exercise on endothelial function.

What inspired you to carry out this research?

Menopause is a biological event that all women experience so we wanted to better understand whether exercise is an effective intervention to combat endothelial dysfunction in postmenopausal women specifically. In general, there is a lack of exercise physiology research conducted in female participants. We recently conducted a different systematic review which found that women encompassed only a third of participants included in exercise-based studies measuring endothelial function (13). In this current study we aimed to summarise what was known about the effect of exercise in postmenopausal women, and more importantly to identify the gaps in our understanding of exercise in this understudied population.

What are the key findings?

Approximately two thirds of all studies investigated found that exercise training does benefit endothelial function of our large and small vessels in postmenopausal women, which is an encouraging finding. However, about a third of the studies did not find a beneficial change in endothelial function with exercise. Several factors may influence the effectiveness of exercise, such as the timing of exercise in relation to the onset of menopause. Women earlier in menopause (one to five years) may experience greater vascular benefits of exercise compared to women later in menopause (more than five years), although more research is required to confirm this.

Do certain types of training, duration and frequency yield greater improvements on endothelial function e.g. aerobic vs resistance?

The studies in this review varied greatly in the type of exercise and population characteristics. We were not able to establish a clear link between duration and frequency of exercise on endothelial function. We were also not able to make strong comparisons between exercise modalities as there are very few studies that have investigated the impact of resistance and alternative forms of exercise on endothelial function. More randomised control trials should be conducted to compare exercise modalities, duration and frequency.

What are the health benefits of exercise for postmenopausal women?

In addition to the cardiovascular benefits of exercise training, postmenopausal women may experience benefits to musculoskeletal function, bone health (14), cognitive function (15, 16), and mental health (17).

From these findings, what are the implications for exercise training strategies for postmenopausal women? Does the current guidance need to be updated?

These findings support encouraging postmenopausal women to engage in exercise to preserve cardiovascular health. Although more research is needed to specify the most effective exercise programs to improve endothelial function. One important thing that we need to determine is whether starting exercise earlier rather than later following menopause may help optimise the beneficial effects on vascular function.

Read the Systematic Review published in Experimental Physiology to find out more about the research and the findings.

References

1. Green DJ, Dawson EA, Groenewoud HM, Jones H, Thijssen DH. Is flow-mediated dilation nitric oxide mediated?: A meta-analysis. Hypertension. 2014;63(2):376-82.
2. Matthys KE, Bult H. Nitric oxide function in atherosclerosis. Mediators Inflamm. 1997;6(1):3-21.
3. Donato AJ, Eskurza I, Silver AE, Levy AS, Pierce GL, Gates PE, et al. Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB. Circulation research. 2007;100(11):1659-66.
4. Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, et al. Age-related reduction of NO availability and oxidative stress in humans. Hypertension. 2001;38(2):274-9.
5. Golden TR, Hinerfeld DA, Melov S. Oxidative stress and aging: beyond correlation. Aging Cell. 2002;1(2):117-23.
6. Ras RT, Streppel MT, Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int J Cardiol. 2013;168(1):344-51.
7. Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. Journal of the American College of Cardiology. 1994;24(2):471-6.
8. Taddei S, Virdis A, Ghiadoni L, Mattei P, Sudano I, Bernini G, et al. Menopause is associated with endothelial dysfunction in women. Hypertension. 1996;28(4):576-82.
9. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340(23):1801-11.
10. Montero D, Padilla J, Diaz-Cañestro C, Muris DM, Pyke KE, Obert P, et al. Flow-mediated dilation in athletes: influence of aging. Medicine & Science in Sports & Exercise. 2014;46(11):2148-58.
11. Early KS, Stewart A, Johannsen N, Lavie CJ, Thomas JR, Welsch M. The Effects of Exercise Training on Brachial Artery Flow-Mediated Dilation: A Meta-analysis. J Cardiopulm Rehabil Prev. 2017;37(2):77-89.
12. Laughlin MH, Newcomer SC, Bender SB. Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. J Appl Physiol (1985). 2008;104(3):588-600.
13. Lew LA, Williams JS, Stone JC, Au AKW, Pyke KE, MacDonald MJ. Examination of Sex-Specific Participant Inclusion in Exercise Physiology Endothelial Function Research: A Systematic Review. Frontiers in Sports and Active Living. 2022;4.
14. Martyn-St James M, Carroll S. High-intensity resistance training and postmenopausal bone loss: a meta-analysis. Osteoporosis International. 2006;17(8):1225-40.
15. Hwang MH. Cognitive Enhancement through Improved Central Artery Stiffness in Postmenopausal Women: Potential Benefit of High-Intensity Aerobic Exercise. Iran J Public Health. 2020;49(8):1571-2.
16. Keawtep P, Wichayanrat W, Boripuntakul S, Chattipakorn SC, Sungkarat S. Cognitive Benefits of Physical Exercise, Physical–Cognitive Training, and Technology-Based Intervention in Obese Individuals with and without Postmenopausal Condition: A Narrative Review. International Journal of Environmental Research and Public Health. 2022;19(20):13364.
17. Fausto DY, Leitão AE, Silveira J, Martins JBB, Dominski FH, Guimarães ACA. An umbrella systematic review of the effect of physical exercise on mental health of women in menopause. Menopause. 2023;30(2):225-34.