Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high‐intensity exercise training are enhanced in the early postmenopausal phase

Abstract

Exercise training leads to favourable adaptations within skeletal muscle; however, this effect of exercise training may be blunted in postmenopausal women as a result of the loss of oestrogens. Furthermore, postmenopausal women may have an impaired vascular response to acute exercise. We examined the haemodynamic response to acute exercise in matched pre- and postmenopausal women before and after 12 weeks of aerobic high intensity exercise training. Twenty premenopausal and 16 early postmenopausal (mean ± SEM: 3.1 ± 0.5 years after final menstrual period) women only separated by 4 years of age (mean ± SEM: 50 ± 0 years vs. 54 ± 1 years) were included. Before training, leg blood flow, O delivery, O uptake and lactate release during knee-extensor exercise were similar in pre- and postmenopausal women. Exercise training reduced (P < 0.05) leg blood flow, O delivery, O uptake, lactate release, blood pressure and heart rate during the same absolute workloads in postmenopausal women. These effects were not detected in premenopausal women. Quadriceps muscle protein contents of mitochondrial complex II, III and IV; endothelial nitric oxide synthase (eNOS); cyclooxygenase (COX)-1; COX-2; and oestrogen-related receptor α (ERRα) were increased (P < 0.05) with training in postmenopausal women, whereas only the levels of mitochondrial complex V, eNOS and COX-2 were increased (P < 0.05) in premenopausal women. These findings demonstrate that vascular and skeletal muscle mitochondrial adaptations to aerobic high intensity exercise training are more pronounced in recent post- compared to premenopausal women, possibly as an effect of enhanced ERRα signalling. Also, the hyperaemic response to acute exercise appears to be preserved in the early postmenopausal phase.

Limb vascular function in women-Effects of female sex hormones and physical activity

“…A similar pattern was observed for infusion of acetylcholine, although the difference between the 2 groups at baseline was smaller. Exercise training improved the amount of eNOS and cyclooxygenase in the muscle of the post‐menopausal women . This finding is in congruence with reports of training‐induced increases in eNOS in ovariectomized animals .…”

“…In endothelial cells from internal mammary artery of post‐menopausal women, eNOS expression is reduced compared to endothelial cells from pre‐menopausal women, and hormone replacement therapy has been shown to increase circulating levels of NO metabolites in post‐menopausal women, suggesting that chronic changes in estrogen levels have implications for the NO system. On the other hand, the protein content of eNOS and prostacyclin synthase in whole muscle homogenate from pre‐ and early post‐menopausal women do not seem to differ . This inconsistency could be linked to the smaller age difference between the pre‐ and post‐menopausal women in the latter study …”

“…On the other hand, the protein content of eNOS and prostacyclin synthase in whole muscle homogenate from pre‐ and early post‐menopausal women do not seem to differ . This inconsistency could be linked to the smaller age difference between the pre‐ and post‐menopausal women in the latter study …”

“…Several studies on rodents, in which vascular function has been assessed in isolated arteries, have demonstrated that exercise training is effective in female ovariectomized rodents . Moreover, 2 recent studies on late pre‐menopausal and early post‐menopausal women, who were on average 3 years within the menopausal transition, have shown that exercise training induces similar, and, for some variables, even better effects on vascular function and markers of vascular function in post‐menopausal compared to pre‐menopausal women . Vascular function was assessed as the change in vascular conductance during femoral arterial infusion of acetylcholine and epoprostenol.…”

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

“…In support of this theory, it has been shown that a period of exercise training increases the expression of ERRα in recent postmenopausal women, but not in premenopausal women, in parallel with a greater increase in the eNOS expression in the recent postmenopausal women, suggesting that activation of the ERRα pathway is of greater importance for the training adaptations in the recent postmenopausal group and that the presence of oestrogen in the premenopausal group may limit the ERRα pathway (Nyberg et al . ). Unpublished observations from our lab also indicate that the expression of ERRα is reduced as a function of years after menopause in sedentary women (see Fig.…”