The exercise timing hypothesis: can exercise training compensate for the reduction in blood vessel function after menopause if timed right?

Abstract

As women enter menopause at mid‐life, oestrogen production ceases and its many beneficial effects on cardiovascular health are lost whereby the age‐related risk of cardiovascular disease is accelerated. Oestrogen acts via oestrogen receptors and can activate the oestrogen response element leading to upregulation of a number of proteins of importance for vascular health, including the vasodilator and anti‐atherogenic enzyme endothelial nitric oxide synthase and angiogenic factors. Hormone replacement therapy can to some extent counteract the loss of oestrogen although studies have shown that such treatment may only be effective if initiated soon after menopause, the so‐called timing hypothesis. An attractive alternative to hormone therapy is regular physical activity, as it is known that exercise induces many of the same cardiovascular health protective effects as oestrogen. Nevertheless, results from studies on the effect of physical activity on vascular function and cardiovascular health are inconsistent, with some studies showing a lack of effect of a physical activity programme and others showing a beneficial effect. The reason for this divergence is unclear but here we explore whether there may be a timing aspect also for exercise training, the exercise timing hypothesis, in which initiation of exercise interventions soon after menopause may be more effective than initiation many years after. The possibility that oestrogen‐related receptor‐α and oxidative stress may play a role in such a timing effect is discussed.

Aerobic High-Intensity Exercise Training Improves Cardiovascular Health in Older Post-menopausal Women

“…In accordance, lifelong well-trained women also have a higher protein level of ERRα in muscle than sedentary age-matched women (Gliemann and Hellsten, 2019). It is thus plausible that the ERRα pathway may be more responsive early after menopause, in particular as ERRα protein appears to be downregulated with time after menopause (Gliemann and Hellsten, 2019). However, the effect of an exercise training intervention on the expression of ERRα in late post-menopausal women has not been examined.…”

Cerebral and peripheral vascular differences between pre- and postmenopausal women

“…Age is an independent determinant of cardiovascular disease (CVD) 1 and is accompanied by increased traditional CVD risk factors, including body mass index (BMI), blood pressure (BP), and cholesterol levels 2 . For women, increased CVD risk coincides with the onset of menopause, characterised by a reduction in the sex hormone oestrogen 3 . As a result, the menopause is associated with a greater decline in peripheral vascular function compared to pre-and peri-menopause via diminished nitric oxide bio-availability at the endothelium 4 .…”

Hypertension is associated with blunted NO-mediated leg vasodilator responsiveness that is reversed by high-intensity training in postmenopausal women

“…Exercise training is considered a cornerstone in the prevention and treatment of hypertension, and has been shown effective to decrease blood pressure in hypertensive postmenopausal women (≥6 years since last menstrual cycle) (16; 40). Despite the suggested decrease in trainability after years with loss of estrogens (9) and lack of change in smooth muscle cell NO responsiveness with training in the forearm of postmenopausal women (27; 35), the smooth muscle cell NO responsiveness may still be trainable in postmenopausal women with hypertension (16), which is supported by a recent observation in hypertensive men (11). However, whether exercise training can improve NO-mediated smooth muscle cell sensitivity in the leg of postmenopausal women is unknown.…”