The postmenopausal phase is associated with an accelerated rate of rise in the prevalence of vascular dysfunction and hypertension; however, the mechanisms underlying these adverse vascular changes and whether exercise training can reverse the decline in vascular function remains unclear. We examined the function of the vascular prostanoid system in matched pre- and postmenopausal women before and after 12 weeks of exercise training. Twenty premenopausal and 16 early postmenopausal (3.1±0.5 [mean±SE] years after final menstrual period) women only separated by 4 (50±0 versus 54±1) years of age were included. Before the training period, the vasodilator response to intra-arterial infusion of either the prostacyclin analog epoprostenol or acetylcholine was lower (≈13%–41%; P <0.05) in the postmenopausal compared with the premenopausal women. Acetylcholine infusion induced a similar release of prostacyclin (6-keto prostaglandin F 1a ). To elucidate the role of vasoconstrictor prostanoids, acetylcholine infusion was combined with the cyclooxygenase inhibitor ketorolac and here the vascular response to acetylcholine was reduced to a similar extent in pre- and postmenopausal women. Exercise training increased ( P <0.05) the vasodilator response to epoprostenol (≈100%–150%) and acetylcholine (≈100%–120%) infusion in the postmenopausal group. These findings demonstrate that the early postmenopausal phase is associated with a marked reduction in vascular function. Despite of a reduced sensitivity to prostacyclin, the overall balance between vasodilator and vasoconstrictor prostanoids does not seem to be altered. Exercise training can reverse the decline in vascular sensitivity to epoprostenol and acetylcholine, suggesting that beneficial vascular adaptations with exercise training are preserved in recent postmenopausal women.

Cardiovascular risk factors are similar in late premenopausal and early postmenopausal women, matched by age and body composition, with the exception that postmenopausal women have higher high- and low-density lipoprotein-cholesterol levels. A 3-month intervention of high-intensity aerobic training reduces risk factors for type 2 diabetes and cardiovascular disease to a similar extent in late premenopausal and early postmenopausal women.

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.

Background The risk of atherothrombotic events increases after the menopause. Regular physical activity has been shown to reduce platelet reactivity in younger women, but it is unknown how regular exercise affects platelet function after the menopause. Objectives To examine the effects of regular aerobic exercise in late premenopausal and recent postmenopausal women by testing basal platelet reactivity and platelet sensitivity to prostacyclin and nitric oxide. Methods Twenty-five sedentary, but healthy, late premenopausal and 24 matched recently postmenopausal women, mean (95% confidence interval) 49.1 (48.2-49.9) and 53.7 (52.5-55.0) years old, participated in an intervention study: 3-month high-intensity supervised aerobic spinning-cycle training (1 h, × 3/week). Basal platelet reactivity was analyzed in platelet-rich plasma from venous blood as agonist-induced % aggregation. In a subgroup of 13 premenopausal and 14 postmenopausal women, platelet reactivity was tested ex vivo after femoral arterial infusion of prostacyclin, acetylcholine, a cyclooxygenase inhibitor, and after acute one-leg knee extensor exercise. Results Basal platelet reactivity (%aggregation) to TRAP-6 (1 μm) was higher in the postmenopausal, 59% (50-68), than the premenopausal women, 45% (35-55). Exercise training reduced basal platelet reactivity to collagen (1 μg mL ) in the premenopausal women only: from 63% (55-71%) to 51% (41-62%). After the training intervention, platelet aggregation was more inhibited by the arterial prostacyclin infusion and the acute exercise in both premenopausal and postmenopausal women. Conclusions These results highlight previously unknown cardioprotective aspects of regular aerobic exercise in premenopausal and postmenopausal women, improving their regulation of platelet reactivity through an increased platelet sensitivity to prostacyclin, which may counterbalance the increased atherothrombotic risk associated with the menopause.

Insulin sensitivity was reduced in early postmenopausal women. However, postmenopausal women increased peripheral insulin sensitivity, skeletal muscle insulin-stimulated glucose uptake, and skeletal muscle mass to the same extent as premenopausal women after 3 months of high-intensity exercise training.

The menopausal transition is accompanied by changes in adipose tissue storage, leading to an android body composition associated with increased risk of type 2 diabetes and cardiovascular disease in post-menopausal women. Estrogens probably affect local adipose tissue depots differently. We investigated how menopausal status and exercise training influence adipose tissue mass, adipose tissue insulin sensitivity and adipose tissue proteins associated with lipogenesis/lipolysis and mitochondrial function. Healthy, normal-weight pre- ( n = 21) and post-menopausal ( n = 20) women participated in high-intensity exercise training three times per week for 12 weeks. Adipose tissue distribution was determined by dual-energy x-ray absorptiometry and magnetic resonance imaging. Adipose tissue glucose uptake was assessed by positron emission tomography/computed tomography (PET/CT) by the glucose analog [18F]fluorodeoxyglucose ([18F]FDG) during continuous insulin infusion (40 mU·m −2 ·min −1 ). Protein content associated with insulin signaling, lipogenesis/lipolysis, and mitochondrial function were determined by western blotting in abdominal and femoral white adipose tissue biopsies. The mean age difference between the pre- and the post-menopausal women was 4.5 years. Exercise training reduced subcutaneous (~4%) and visceral (~6%) adipose tissue masses similarly in pre- and post-menopausal women. Insulin-stimulated glucose uptake, assessed by [18F]FDG-uptake during PET/CT, was similar in pre- and post-menopausal women in abdominal, gluteal, and femoral adipose tissue depots, despite skeletal muscle insulin resistance in post- compared to pre-menopausal women in the same cohort. Insulin-stimulated glucose uptake in adipose tissue depots was not changed after 3 months of high-intensity exercise training, but insulin sensitivity was higher in visceral compared to subcutaneous adipose tissue depots (~139%). Post-menopausal women exhibited increased hexokinase and adipose triglyceride lipase content in subcutaneous abdominal adipose tissue. Physical activity in the early post-menopausal years reduces abdominal obesity, but insulin sensitivity of adipose tissue seems unaffected by both menopausal status and physical activity.

BackgroundWe examined the role of menopause on cardiac dimensions and function and assessed the efficacy of exercise training before and after menopause.Methods and ResultsTwo groups of healthy premenopausal (n=36, 49.4±0.3 years) and postmenopausal (n=37, 53.5±0.5 years) women with no history of cardiovascular disease and with a mean age difference between groups of only 4 years were studied. Cardiac dimensions and systolic and diastolic function were determined by transthoracic echocardiography with tissue Doppler imaging and 2‐dimensional speckle tracking. Measurements were performed at baseline and after a 12‐week period of high‐intensity aerobic cycle training. LV internal diastolic diameter and LV mass were similar in the 2 groups at baseline and increased by ≈2% to 8% (P=0.04–0.0007) with training in both groups. Left atrial end‐diastolic and end‐systolic volumes were similar for both groups and increased by 23% to 36% (P=0.0006–0.0001) with training. Systolic function assessed by mean global strain was similar in both groups at baseline and increased by ≈8% (P=0.0004) with training in the postmenopausal group. LV displacement increased by ≈3% (P=0.04) in the premenopausal women only. Diastolic function assessed by E/A ratio was similar at baseline and increased by ≈7% (P=0.01) in the premenopausal group and 11% (P=0.0001) in the postmenopausal group with training.ConclusionsThese results suggest that training‐induced cardiac adaptations are preserved in the early postmenopausal phase. Furthermore, the hormonal changes associated with the menopausal transition do not appear to affect cardiac dimensions and function.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02135575.

The influence of the menopausal transition, with a consequent loss of oestrogen, on capillary growth in response to exercise training remains unknown. In the present study, we evaluated the effect of a period of intense endurance training on skeletal muscle angiogenesis in late pre-menopausal and recently post-menopausal women with an age difference of <4 years. Skeletal muscle biopsies were obtained from the thigh muscle prior to and after 12 weeks of intense aerobic cycle training, and analyzed for capillarization, fiber type distribution and content of vascular endothelial growth factor (VEGF). At baseline, there was no difference in capillary per fiber ratio (C:F; 1.41 ± 0.22 vs 1.40 ± 0.30), capillary density (CD; 305±61 vs 336±52 mm2), muscle fiber area (MFA) or percentage distribution of muscle fiber type I (47.3±10.1 vs 49.3±15.1 %) and type II (52.7±10.1 vs 50.7±15.1%) between the pre- and post-menopausal women. The training period resulted in a similar increase in C:F in pre- and post-menopausal women (by 9.2 vs 12.1 %, respectively) and CD (by 6.9 vs 8.9 %, respectively), whereas MFA and fiber type distribution remained unaltered. Skeletal muscle VEGF protein content was similar between groups at baseline and increased to a similar extent with training (by 21.1 vs 27.2 %, respectively) in the pre- and post-menopausal women. In conclusion, the loss of oestrogen per se at menopause does not influence the capillary growth response to intense aerobic exercise training.