1. Exercise and adult women’s health
Amos Pines

2. Ordinary exercise testing
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)

3. 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

4. Exercise improves cardiovascular 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
Looking at the major metabolic risk factors for cardiovascular disease, it appears that all of them may be improved by exercise. These include weight loss, reduction in total body fat and abdominal fat, smaller waist circumference (now regarded as an important risk factor in women), better glucose metabolism, lower triglycerides and higher high density lipoprotein (HDL), improved endothelial function and a thinner arterial intima-media width.
IMPROVED

5. 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 ± ± 1.8
Body weight (kg) 73.7 ± ± ± ± 2.83*
Lean body mass (kg) 41.7 ± ± ± ± 1.7
Fat mass (kg) 30.0 ± ± ± ± 3.5*
% Body fat 42.3 ± ± ± ± 2.0*
BMI (kg/m2) 27.1 ± ± ± ± 1.4*
Waist-hip ratio 0.84 ± ± ± ± 0.02
VO2-max (ml/kg/min) 26.5 ± ± ± ± 2.8*
MHR (bpm) 165 ± ± ± ± 3.7
MRQ 1.19 ± ± ± ± 0.03 ˙
One of many studies showing the benefits of regular exercise on basic parameters. Weight loss, decrease in fat mass, lower body mass index, and better oxygen consumption are expected.
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

6. 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:
Effects of exercise on waist circumference, glucose, SBP, DBP, TG, HDL-c

7. 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
Cardiovascular morbidity is naturally the primary target of any exercise program. Here are data from the huge cohort of the WHI observational trial, clearly demonstrating that there is a good dose response between cardiovascular events and exercise. The more active, the less risk. Women in the highest physical activity quartile had up to 45% lower risk for cardiovascular events as compared with sedentary women, but even a slight increase in the degree of energy expenditure (quartile 1) already showed a beneficial effect.
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

8. 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
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
1.06
1.00
1.00
0.86
0.76
0.73
0.57
0.58
Relative risk of casrdiovascular disease
0.40
Rarely or never 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

9. 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

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

11. 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 Respiratory Physical activity deaths deaths causes of death deaths (hours/week) (n = 923) (n = 2727) (n = 1040) (n = 181)
These are the results of a 16-year follow-up from the Nurses’ Health Study database. At baseline, the mean age was 48 years. The table shows better survival rates for all women who exercise regularly. Physical activity was measured as hours per week. Cardiovascular death, respiratory death, other causes of death, and even cancer death were fewer in physically active women.
<
2– (0.62–0.88) 0.85 (0.76–0.94) 0.57 (0.48–0.67) 0.46 (0.34–0.63)
≥ (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

12. Fitness and mortality The Lipid Research Clinics Study
Time to max. heart rate Number of Age-adjusted death rate (min) deaths (per 100,000 person-years)
All cause death 1.3– – –
CVD death 1.3– – –
These are data from the Lipid Research Clinics Study. Women in a wide age range were followed for more than 20 years. Fitness was measured by the Bruce tread-mill protocol. If one is physically fit, more exercise would be needed until the maximal heart rate is reached. The table shows that total mortality and cardiovascular mortality are significantly lower in those who exercised longer.
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
Stevens J, et al. Am J Epidemiol 2002;156:832

13. 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 (1.27, 1.61) 1.58 (1.39, 1.80) < 0.001
With BMI (1.18, 1.51) 1.43 (1.26, 1.63) < 0.001
The Nurses’ Health Study experience points at the association of physical activity and morbidity from coronary heart disease. A recent publication in Circulation showed that sedentary women (engaged in exercise less than 1 hour per week) had 50% increased risk for coronary artery disease as compared to very active women (spending more than 3.5 hours per week on exercise).
Li TY, et al. Circulation 2006;113:499

14. Fitness and mortality in healthy women > 70 years old
Prognosis is associated with ability to perform and speed during a 400-m corridor walk: Better survival for those who walk faster 70 60 50 40 30 20 10
Excluded
Stopped
Quartile 1
Quartile 2
Quartile 3
Quartile 4
Quartile 1- the best performers
Quartile 4 – the worst performers
Mortality (%)
Years
p < 0.001
Newman AB, et al. JAMA 2006;295:2018

15. Exercise and BMD: conflicting results
4 years of progressive strength training showed a positive correlation with BMD changes Osteoporosis 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 forearm Osteoporosis Int 2006;17:133
1-year program showed site-specific responses to upper and lower body exercise training Bone 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
There are many studies which have investigated a possible positive effect of exercise on bone density. However, the results are conflicting, perhaps because of the employment of different exercise protocols.

16. Relative risks of death from any cause among participants with various risk factors who 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

17. 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 Musculoskelet Disord 2012;13:177 

18. 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 

19. Exercise and fracture 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
Relative risk (95% CI)
< 3 3–8.9 9– –23.9 >24
Activity, MET hours/week
Feskanich D, et al. JAMA 2002;288:2300

20. Exercise and fracture 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 –
BMD total hip < g/cm –
Physical activity score < –
Left grip strength < 0.60 bar –
Age > 65 years –
Maternal history of fragility fracture –
Past falls –
Albrand G, et al. Bone 2003;32:78

21. 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)
Falls Rate (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 injuries Rate (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)
One of the best ways to prevent fractures in the elderly is to implement measures to reduce the risk of falls. Exercise may prevent falls. In this study the intervention subjects attended a median of 23 weekly exercise classes over the year, and most undertook the home exercise sessions at least weekly. At retest, the exercise group performed significantly better than the controls in three of six balance measures. The groups did not differ at retest in measures of strength, reaction time and walking speed. However, within the 12-month trial period, the rate of falls in the intervention group was 40% lower than that of the control group.
Barnett A, et al. Age Aging 2003;32:407

22. Exercise decreases breast 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 per week
Monninkhof EM, et al. Epidemiology 2007;18:137

23. 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
High body mass index (BMI) is a known risk factor for breast cancer. In this recent study, in a fairly large cohort and 10-year follow-up, 4 hours/week of vigorous exercise resulted in 22% reduced risk for breast cancer compared to non-active women. Those characterized by the triad of the highest energy intake, that is eating too many calories, the highest BMI, and having the lowest energy expenditure, that is physically inactive, had two-fold risk for breast cancer as compared to those with the most favorable relevant data.
Chang SC, et al. Cancer Epidemiol Biomarkers Prev 2006;15:334

24. 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 

25. 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 risk or strenuous activity ≥ 20 min) of women (95% CI)
None 12,
Some 35, (0.74–0.82)
2–4 17, (0.62–0.71)
> 4 27, (0.53–0.59)
Wassertheil-Smoller S, et al. Arch Intern Med 2004;164:289

26. 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
Time (years)
Wassertheil-Smoller S, et al. Arch Int Med 2004;164:289

27. Exercise and dementia 1740 participants Mean age 74, 60% women
Incidence of dementia – 13/1000 person-years for those who exercised 3+ times/week vs 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
Exercise has beneficial effects on cognitive function. This recent study clearly shows that as much as three weekly sessions of 15 minutes physical activity of any sort, during a 6-year follow-up in an elderly population, are associated with a reduction in the incidence of dementia from 20 cases per 1000 person-years to 13 cases per 1000 person-years.
Age during the study (years)
Larson EB, et al. Ann Intern Med 2006;144:73

28. 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
Quality of life is perhaps the most important aspect of menopause medicine. This slide shows a graded positive effect of exercise on the classical symptoms of menopause. The total severity score of symptoms is significantly reduced as the degree of physical activity is increased.
Elavsky S, McAuley E. Maturitas 2005;52:374

29. Exercise is associated with 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!!!
Sleep quality is a major component of quality of life. This study recruited overweight, sedentary women, aged 50-75, and divided them into a group instructed to do low-intensity stretchings and those who started moderate-intensity exercise sessions. After 1 year, there was a significant difference between morning exercisers, > 225 minutes per week, and the low-intensity stretchers in regard to ability to fall asleep and in sleep duration. As a curiosity, evening exercisers had more trouble falling asleep.
Tworoger SS, et al. Sleep 2003;26:830

30. Vasomotor symptoms and exercise: the MsFLASH study 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 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.

31. Exercise affects sex 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
This slide presents a summary of the association of exercise with the concentration of sex hormones in serum. The WHI Dietary Modification Trial data confirm what has long been known, that the higher the body mass index (BMI), the higher the level of estrone, estradiol, etc. On the other hand, exercise is linked with reduction in sex hormone levels. This may explain the association between exercise and lower incidence of breast cancer.
McTiernan A, et al. Obesity 2006;14:1662

32. 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

33. How much exercise is 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

34. Recommended levels of exercise required to improve physical activity and 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

35. 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 women had a first CHD event, had a first CVA event, and 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.
Absolute risks and 95% group-specific confidence intervals (gsCI) for incident vascular diseases, by strenuous and any physical activity, excluding the first 4 years of follow-up.
Miranda E. G. Armstrong et al. Circulation. 2015;131:

36. 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 may potentially carry a risk of injuries and adverse events. Not all middle-aged or elderly people are able to exercise because of various disease conditions and disabilities. Exercise may cause pain and damage in the musculo-skeletal and articular system. The mood-elating effects of exercise through the secretion of endorphins may lead to addiction to strenuous or too long exercise sessions. As already mentioned, exercise lowers adiposity and the level of estrogen, while increasing the level of sex hormone binding globulin. Under such circumstances, hot flushes and other vasomotor symptoms might become more severe in very physically active women.

37. 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

38. 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

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

40. 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: