Exercise and adult women’s health

Exercise and adult women’s health Amos Pines

Be fit – be healthy Ways to measure fitness: Ordinary exercise testing Walk test Parameters used to measure the intensity of exercise: • Heart rate • Oxygen consumption (VO2) • Energy expenditure (METs or k/cal spent during a time unit)

Measuring energy expenditure 1 Metabolic Equivalent Task (MET) = calories spent while resting(the individual basal metabolic rate (BMR) is adjusted for body size) The intensity of physical activity is measured by METs per time unit: 2 METs/h means spending twice the calories needed at rest during 1 hour

Exercise improvescardiovascular risk profile • Body mass index • Total, abdominal (subcutaneous and visceral) fat • Waist circumference • Glucose metabolism/insulin resistance • Blood pressure • Lipids • Endothelial function/intima-media thickness IMPROVED

Benefits of exercise in postmenopausal women 70% maximal heart rate; 45 minutes; 3-4 times weekly for 6 months Control (n = 13) Exercise (n = 10) Pre Post Pre Post Age (years) 59.1 ± 1.5 58.0 ± 1.8 Body weight (kg) 73.7 ± 4.07 73.7 ± 4.30 67.4 ± 2.76 64.4 ± 2.83* Lean body mass (kg) 41.7 ± 1.4 41.8 ± 1.6 40.6 ± 1.6 40.7 ± 1.7 Fat mass (kg) 30.0 ± 3.1 30.0 ± 3.2 26.9 ± 3.4 23.6 ± 3.5* % Body fat 42.3 ± 2.2 41.2 ± 1.9 39.3 ± 1.2 36.1 ± 2.0* BMI (kg/m2) 27.1 ± 1.4 27.1 ± 1.4 24.6 ± 1.1 23.6 ± 1.4* Waist-hip ratio 0.84 ± 0.03 0.83 ± 0.03 0.77 ± 0.03 0.77 ± 0.02 VO2-max (ml/kg/min) 26.5 ± 1.4 26.4 ± 1.4 28.7 ± 1.9 34.9 ± 2.8* MHR (bpm) 165 ± 3.7 163 ± 4.0 162 ± 4.2 166 ± 3.7 MRQ 1.19 ± 0.03 1.20 ± 0.02 1.21 ± 0.04 1.25 ± 0.03 • ˙ Values are mean ± SE. MRQ, maximal respiratory quotient; MHR, maximal heart rate *p < 0.05 (significant changes with exercise and significantly different from the control group) • Santa-Clara H, et al. Metabolism 2006;55:1358–64

Exercise and the Metabolic Syndrome: DREW Study data.Sedentary, overweight, moderately hypertensive PMW; 6 months of exercise training at 50%, 100%, 150% of the NIH Recommendations for physical activity (4, 8, and 12 kcal/kg of energy expenditure/wk [KKW]) vs. nonexercise controls. Earnest CP, et al. Am J Cardiol 2013;111:1805-11. Effects of exercise on waist circumference, glucose, SBP, DBP, TG, HDL-c

Exercise and cardiovascular morbidity The WHI observational trial data: • Up to 45% decreased risk for cardiovascular events, correlated with the degree of energy expenditure (MET) • 1.2 • 1.0 • 0.8 • 0.6 • 0.4 • 0.2 • 0.0 • 1.00 • 0.85 • 0.70 • 0.66 • 0.55 • 1 2 3 4 5 • Lowest Highest • Quintile of total MET score • White women (n = 61,574) • p < 0.001 • Manson JE, et al. N Engl J Med 2002;347:716

WHI observational study: CV events inversely correlated with walking pace • Adjusted for age and walking time (p < 0.001) • Multivariate (p = 0.002) • 1.07 • 1.06 • 1.1 • 1.0 • 0.9 • 0.8 • 0.7 • 0.6 • 0.5 • 0.4 • 0.3 • 0.2 • 0.1 • 0.0 • 1.00 • 1.00 • 0.86 • 0.76 • 0.73 • 0.58 • 0.57 • Relative risk of casrdiovascular disease • 0.40 • Rarely ornever walk(n = 10,896) • < 2 mph(easy casual)(n = 10,690) • 2–3 mph(average)(n = 30,523) • 3–4 mph(brisk)(n = 17,555) • > 4 mph(very brisk)(n = 990) • Walking pace (mph) among walkers • Manson JE, et al. NEJM 2002;347:716

WHI observational study data: physical activity and death rate Seguin R, et al. Am J Prev Med 2014;46:122-35 Physical functioning – a subjective score - whether current health limits physical function

WHI observational study dataSeguin R, et al. Am J Prev Med 2014;46:122-35 Sedentary time – daily sitting time plus lying time minus sleeping time

Exercise and mortality The Nurses’ Health Study data:the more active, the better prognosis(mean age at baseline 48 years) • Relative risk (95% confidence interval) • Non-cancer, non-cardiovascular, Cardiovascular Cancer non-diabetes RespiratoryPhysical activity deaths deaths causes of death deaths(hours/week) (n = 923) (n = 2727) (n = 1040) (n = 181) • < 1 1.0 1.0 1.0 1.0 • 2–3.9 0.74 (0.62–0.88) 0.85 (0.76–0.94) 0.57 (0.48–0.67) 0.46 (0.34–0.63) • ≥ 7 0.69 (0.49–0.97) 0.87 (0.72–1.04) 0.46 (0.33–0.64) 0.23 (0.11–0.50) • Rockhill B, et al. Am J Public Health 2001;91:578

Fitness and mortalityThe Lipid Research Clinics Study n = 2506; age 30-75; > 20 years follow-up Fitness measured by the time to produce a predicted maximal heart rate. The shorter, the better prognosis Method of testing: Bruce protocol • Fitness • Time to max. heart rate Number of Age-adjusted death rate(min) deaths (per 100,000 person-years) • All cause death1.3–5.6 208 7.67.1–8.0 80 6.09.3–13.0 33 4.8 • CVD death1.3–5.6 89 2.87.1–8.0 30 2.29.3–13.0 7 0.9 • Stevens J, et al. Am J Epidemiol 2002;156:832

Exercise and CHD morbidity The Nurses’ Health Study data: the more active, the less CHD morbidity Multivariate Physical activity (hours/week)relative risk ≥ 3.5 1–3.49 < 1 p Without BMI 1.00 1.43 (1.27, 1.61) 1.58 (1.39, 1.80) < 0.001 With BMI 1.00 1.34 (1.18, 1.51) 1.43 (1.26, 1.63) < 0.001 • Li TY, et al. Circulation 2006;113:499

Fitness and mortalityin healthy women > 70 years old Prognosis is associated with ability to performand speed during a 400-m corridor walk: Better survival for those who walk faster • 70 • 60 • 50 • 40 • 30 • 20 • 10 • 0 • Excluded • Stopped • Quartile 1 • Quartile 2 • Quartile 3 • Quartile 4 • Quartile 1- the best performers • Quartile 4 – the worst performers • Mortality (%) • 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 • Years • p < 0.001 • Newman AB, et al. JAMA 2006;295:2018

Exercise and BMD:conflicting results • 4 years of progressive strength training showed a positive correlation with BMD changesOsteoporosis Int 2005;16:2129 • 3 years of low-volume, high-resistance strength training and high-impact aerobics maintained BMD at the spine, hip and calcaneus, but not at the forearmOsteoporosis Int 2006;17:133 • 1-year program showed site-specific responses to upper and lower body exercise trainingBone 2006;July, available online • “The exercise protocols that were used in this individual patient data meta-analysis do not improve femoral neck BMD”Am J Obstet Gynecol 2006;194:760

Relative risks of death from any causeamong participants with various risk factorswho achieved an exercise capacity of less than 5 METs (metabolic equivalents) or 5–8 METs, as compared with participants whose exercise capacity was more than 8 METs 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 > 8 METs (n = 2743) 5–8 METs (n= 1885) < 5 METs (n = 1585) Relative risk of death • Hypertension COPD Diabetes Smoking BMI TC • Warburton DER, et al. CMAJ 2006;174:961

Exercise and BMD: A meta-analysis 25 studies representing 63 groups (35 exercise, 28 control) and final assessment of femoral neck (FN) and/or lumbar spine (LS) BMD in 1775 participants. Overall, there was a statistically significant benefit of ground and/or joint reaction force exercise on FN BMD. Overall, there was a statistically significant benefit in LS BMD but slightly overlapping 95% Cis. While the magnitude of change in FN and LS BMD might be considered small at the FN and trivial at the LS, they appear to be clinically important. Based on previous prediction models, the exercise-induced changes in BMD observed at the FN and LS in the current meta-analysis would reduce the 20-year relative risk of osteoporotic fracture at any site by approximately 11% and 10%, respectively. Kelley GA, et al. BMC MusculoskeletDisord 2012;13:177

Effect of leisure-time physical activity on BMD 2,903 premenopausal and 2,267 postmenopausal women in Korea. Leisure-time physical activity levels were assessed by a self-administrated questionnaire. Regardless of menopausal status, performing more than moderate levels of leisure-time physical activity or total MET score had a significant positive association with BMD at both the lumbar spine and femur. In the premenopausal group, women whose total MET score was 1,050-1,500 (MET-min/week) appeared to have the highest lumbar spine and femoral BMD (p < 0.001). Kim KZ, et al. Calcif Tissue Int. 2012;91:178-85

Exercise andfracture risk • 12-year follow-up from the Nurses’ Health Study 61,200 healthy women; 415 incidental hip fractures • Risk lowered by 6% for each increase in activity equivalent to 1 hour of walking/week at an average pace, compared to sedentary women BMI < 25 > 25 1.2 1.0 0.8 0.6 0.4 0.2 0 Relative risk (95% CI) < 3 3–8.9 9–14.9 15–23.9 >24 Activity, MET hours/week • Feskanich D, et al. JAMA 2002;288:2300

Exercise andfracture risk • 672 healthy women (mean age 59);mean follow-up 5.3 years; annual incidence of osteoporotic fractures 21/1000 women/year • Odds ratio for fracture was doubled in women with low physical activity Variable OR 95% CI p Personal history of fragility fracture after 45 years 3.33 1.42–7.79 0.006 BMD total hip < 0.736 g/cm2 3.15 1.75–5.66 0.001 Physical activity score < 14 2.08 1.17–3.69 0.01 Left grip strength < 0.60 bar 2.05 1.15–3.64 0.01 Age > 65 years 1.90 1.04–3.47 0.04 Maternal history of fragility fracture 1.77 1.01–3.09 0.04 Past falls 1.76 1.00–3.09 0.05 • Albrand G, et al. Bone 2003;32:78

Exercise prevents falls • 150 participants • Mean age 75, 70% women • Intervention: weekly exercise classes and home training • Results: better performance in balance tests • 40% less falls during 12 months Intervention Control Risk (n = 76) (n = 74) (95% CI) FallsRate 0.605 0.946 0.60 (0.36–0.99)One or more 35.5% 50.0% 0.71 (0.49–1.04)Two or more 10.8% 24.3% 0.44 (0.21–0.96) Falls injuriesRate 0.395 0.541 0.66 (0.38–1.15)One or more 28.9% 37.8% 0.77 (0.48–1.21)Two or more 7.9% 13.5% 0.58 (0.22–1.52) • Barnett A, et al. Age Aging 2003;32:407

Exercise decreasesbreast cancer risk • Numerous studies showed an inverse modest correlation (15–20% decrease) between physical activity and postmenopausal breast cancer risk • A trend analysis indicated a 6% decrease in breast cancer risk for each additional hour of physical activity perweek • Monninkhof EM, et al. Epidemiology 2007;18:137

Exercise and breast cancer risk • High calorie intake and high BMI are known risk factors for breast cancer in postmenopausal women • 38,660 women (age 55–74); 10-year follow-up • > 4 hours/week of vigorous physical activity resulted in 22% reduced risk for breast cancer as compared to non-actives • Women with the most unfavorable energy balance (high energy intake, high BMI, physically inactive) demonstrated a two-fold risk versus those with most favorable data • Chang SC, et al. Cancer Epidemiol Biomarkers Prev 2006;15:334

Physical activity across the life course and risk of breast cancer Among post-menopausal women, each of [22.9 MET-h/week of mean lifetime leisure-time moderate to vigorous intensity physical activity (MVPA) (equivalent to running for 3 h/w) and [61.1 MET-h/week of mean lifetime household MVPA (equivalent to 24 h/w of moderate household work) reduced breast cancer risk by 40 %, compared to 0 MET-h/week of each. The respective ORs were 0.63 (95 % CI 0.42–0.94) and 0.58 (95 % CI 0.43–0.79). The weekly volume of leisure-time MVPA required to reduce post-menopausal breast cancer risk was consistent with amount recommended in the American Institute for Cancer Research guidelines for cancer prevention. Kobayashi LC, et al. Breast Cancer Res Treat 2013;139:851–861

Depression and mortality • WHI observational study (93,676 women, followed 4.1 years). Depression was measured by a short form of the Center for Epidemiological Studies Depression Scale • Depression was associated with higher mortality Exercise (episodes/week of moderate Number Relative riskor strenuous activity ≥ 20 min) of women (95% CI) None 12,637 1.00 Some 35,648 0.78 (0.74–0.82) 2–4 17,093 0.67 (0.62–0.71) > 4 27,251 0.56 (0.53–0.59) • Wassertheil-Smoller S, et al. Arch Intern Med 2004;164:289

Exercise and depression • WHI observational study (93,676 women, followed 4.1 years). Depression was measured by a short form of the Center for Epidemiological Studies Depression Scale • Exercise reduces the risk of depression • Stroke Cardiovascular disease All-cause mortality • 1.00 • 0.99 • 0.98 • 0.97 • 0.96 • 0.95 • Depressed • Not depressed • Proportion • 0 1 2 3 4 5 • 0 1 2 3 4 5 • 0 1 2 3 4 5 • Time (years) • Wassertheil-Smoller S, et al. Arch Int Med 2004;164:289

Exercise and dementia • Incidence of dementia – 13/1000 person-years for those who exercised3+ times/week vs. 19.7 for those engaged in physical activity < 3 times/week • 1740 participants • Mean age 74, 60% women • Mean follow-up 6.2 years • Comparing those exercising < 3 vs. 3+ times weekly (defined as > 15 min of any sort of activity) • 1.00 • 0.75 • 0.50 • 0.25 • 0.00 ≥ 3 times per week < 3 times per week • Dementia-free • 65 70 75 80 85 90 95 100 • Age during the study (years) • Larson EB, et al. Ann Intern Med 2006;144:73

Exercise improves quality of life • 60 women, mean age 54 • Low active vs. moderate active vs. high active Total frequency of symptoms (score) 103 vs. 90 vs. 76 Psychological 43 vs. 38 vs. 32 Vasosomatic 32 vs. 25 vs. 21 General somatic 29 vs. 27 vs. 23 Total severity (score) 105 vs. 87 vs. 73 • Elavsky S, McAuley E. Maturitas 2005;52:374

Exercise is associatedwith better sleep • Overweight, sedentary, non-users of HRT, aged 50–75 • A year-long study comparing moderate-intensity exercise to low-intensity stretching • Morning exercisers, > 225 minutes/week, had 3-fold less trouble of falling asleep and longer sleep duration vs. those stretching • Evening exercisers had more trouble falling asleep!!! • Tworoger SS, et al. Sleep 2003;26:830

Vasomotor symptoms and exercise: the MsFLASHstudy data Sternfeld B, et al. Menopause 2014;21:330-8 Late perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms (VMS); 12 weeks of three individualized cardiovascular conditioning training sessions per week; on a treadmill, an elliptical trainer, or a stationary. bicycle; target heart rate was 50%-60% of heart rate reserve for the first month and 60%-70% (approximately 125-145 beats/min) for the remainder of the intervention. Conclusions: The trial provides strong evidence that aerobic exercise training in previously sedentary women does not significantly alleviate frequent or bothersome VMS. Exercise training improves fitness level, is safe and well tolerated, and may slightly improve subjective sleep quality and symptoms of insomnia and depression.

Exercise affectssex hormone levels • Data from the Women's Health Initiative Dietary Modification • Trial: BMI was positively associated with estrone, estradiol, free estradiol, free testosterone, prolactin, but was negatively associated with SHBG • Total physical activity (METs per week) was negatively associated with concentrations of estrone, estradiol, and androstenedione • Lowest hormonal levels recorded in women with low BMI/high physical activity McTiernan A, et al. Obesity 2006;14:1662

Counseling on exercise • Mean age 57 years; 67% women; 12 months follow-up Conclusion: counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months • Raina Elley C, et al. BMJ 2003;326:793

How much exerciseis needed? • The specific dose of physical activity, in terms of frequency, intensity, and duration, and the related volume of energy expenditure that is effective in achieving specific biological or clinical outcomes are still partially understood • Recommendations for women are usually defined as at least three 30-min sessions/week of moderate intensity physical activity, which corresponds to expending about 600 kcal/week (7–10 METs/week) • Blair SN. Arch Intern Med 2005;165:2324

Recommended levels of exercise required to improve physical activityand fitness levels for health benefits • Moderate-intensity aerobic exercise • 40–59% of heart rate reserve, or about 4–6 METs • 20–60 min per day • 3–5 days per week • Examples: brisk walking (15–20 min per mile), dancing • Detailed prescription for recommended levels of aerobic, resistance and flexibility exercise may be found in CMAJ 2006;174:961–74 Warburton DER, et al. CMAJ 2006;174:961–74

Too much exercise (i.e. daily) may not be beneficial: incident vascular diseases, by strenuous and any physical activity, excluding the first 4 years of follow-up. Million Women Study, women attending NHS breast cancer screening clinics. 9 years follow-up. 49113 women had a first CHD event, 17822 had a first CVA event, and 14550 had a first VT event. In comparison with inactive women, those reporting moderate activity had significantly lower risks of all 3 conditions. However, women reporting strenuous physical activity daily had higher risks. Miranda E. G. Armstrong et al. Circulation. 2015;131:721-729

Adverse consequences of exercise • Even moderate exercise may be harmful to the musculo-skeletal-articular system • Strenuous exercise may be dangerous to the cardiovascular system • Too much exercise may be addictive • Exercise may lead to hormonal changes with a decrease in free estradiol and worsening of hot flushes

Exercise in the menopause: conclusions • Any physical activity is better than being sedentary • Regular exercise reduces total and cardiovascular mortality • Better metabolic profile, balance, muscle strength, cognition and quality of life are observed in physically active persons • Heart events, stroke, fractures and breast cancer are significantly less frequent • Benefits far overweigh possible adverse consequences: the more – the better, but too much may cause harm

Exercise in the menopause: conclusions • Optimal exercise prescription: at least 30 minutes of moderate-intensity exercise, at least 3 times weekly • Two additional weekly training sessions of resistance exercise may provide further benefit • Injury to the musculo-skeletal-articular system should be avoided

Physical activity across the life course and risk of cancer PMID:25690300 2015;

Exercise and the Metabolic Syndrome: DREW Study data.Sedentary, overweight, moderately hypertensive PMW; 6 months of exercise training at 50%, 100%, 150% of the NIH Recommendations for physical activity (4, 8, and 12 kcal/kg of energy expenditure/wk [KKW]) vs. nonexercise controls. Earnest CP, et al. Am J Cardiol 2013;111:1805-11.

Exercise and adult women’s health