Increased adiposity negatively impacts health including overall mortality; a wide range of chronic diseases including diabetes, coronary heart disease and cancer; and a poor quality of life.^{1, 2, 3, 4} Overweight and obesity are prevalent worldwide,^{5, 6, 7} exceeding 60% in the United States,⁷ and globally their rates are increasing.^{8, 9, 10, 11, 12} Thus, developing and testing interventions to treat this condition is a priority, particularly in the context of effecting downstream chronic diseases. The high prevalence of overweight and obesity among postmenopausal women, nearing 50% in countries such as Canada,¹³ increases their risk for the many adverse consequences of increased adiposity.¹⁴

Intervening with physical activity may be particularly appropriate in this population. Physical activity seems to be efficacious for weight stability without intervening on diet, but because of the paucity of large trials in postmenopausal women, it is unclear whether it can lead to a significant reduction in adiposity in this population.^{1, 15, 16, 17, 18, 19} Numerous observational studies suggest that physical activity reduces the risk of postmenopausal breast cancer,^{20, 21, 22} and that activity carried out after menopause continues to lead to a reduction in risk.^{1, 23, 24, 25} This effect may operate through a reduction in adiposity (postmenopausal breast cancer risk could be lowered by as much as 20%^{26, 27}or more²⁸ with at least 10 kg weight loss), but there also seem to be effects over and above a reduction in adiposity.¹ Other than alcohol intake, few modifiable breast cancer risk factors are known.²⁹

The Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial was designed to increase the understanding of the biological mechanisms that mediate the inverse association between physical activity and breast cancer risk. Specifically, it used a randomized, controlled design with a large sample size to examine whether an intensive aerobic exercise intervention influenced the primary end points of adiposity and endogenous sex hormone concentrations, as well as the secondary end points of mammographic density, insulin-like growth factors, insulin resistance and circulating markers of obesity and inflammation. We previously reported the results from this trial on the sex hormones outcomes.³⁰ This paper reports the effects of the exercise intervention on both total and abdominal adiposity, as assessed with dual X-ray absorptiometry and computed tomography. It addresses a gap in the scientific literature for randomized controlled trials carried out in postmenopausal women of exercise interventions that have higher volume and longer duration and that quantify adiposity with direct imaging methods.³¹ The ALPHA trial also assessed the effect of physical activity independent of a dietary intervention on potential breast cancer risk mediators in order to extend scientific understanding of the mechanisms underlying risk reduction.

Of 3454 women assessed for eligibility, 1965 did not meet the inclusion criteria, 274 were excluded for other reasons, 895 refused participation and 320 women were randomized, with 165 women from Edmonton and 155 from Calgary (Figure 1). Baseline characteristics of the two groups were similar (Table 1). Nine women were lost to follow-up, one died for reasons unrelated to the trial and eight were no longer interested or too busy. Over the course of the trial no adverse events or side effects were reported in women randomized to the exercise intervention.

Women in the exercise group completed an average of 3.6 sessions per week (s.d.=1.3) for a mean duration of 178.5 min (s.d.=76.1).³⁰ Objectively measured average heart rate was 62.2% (s.d.=9.8) of the estimated heart rate reserve. As assessed using the Past Year Total Physical Activity Questionnaire, 23% (37/160) of controls reported at least 150 min per week of total activity over the intervention year; however, recreational activity increased far less in controls than in exercisers (3.2 vs 20.2 MET-hours per week; P<0.001).^{40, 41} Furthermore, aerobic fitness increased significantly more in exercisers than in controls (3.9 vs 0.7 ml kg⁻¹ min⁻¹; P<0.001, corresponding to a per cent change of 14.2 vs 2.6%). Mean energy intake decreased among controls relative to exercisers (161 vs 45 kcal per day; P=0.01).

The mean decrease in adiposity between baseline and 1 year was significantly greater in exercisers relative to the controls (P<0.001) (Table 2). Exercisers lost 2.3 kg body weight, corresponding to a 3.0% decrease, whereas controls lost 0.5 kg, equal to a 0.6% decrease. The body weight lost largely constituted of body fat; exercisers lost 2.4 kg body fat, corresponding to a 7.7% decrease, whereas controls lost 0.4 kg, equal to a 1.3% decrease. Abdominal fat area decreased in exercisers, with a mean of 48.5 cm², of which 16.5 cm² was intra-abdominal fat area; controls also experienced a small mean decrease in abdominal fat area (9.6 cm²) of which 1.6 cm² was intra-abdominal fat area. The only nonstatistically significant difference was in lean body mass, which did not decrease among exercisers, but did decrease by 0.1 kg in the control group. If the few participants with missing outcome data were included by assuming no change, or if the baseline value of the outcome measure and covariates were included, the results were similar (data not shown).

The association between the intervention and change in adiposity was similar in each BMI stratum (P-value for interaction terms>0.05; data not shown). The results stratified by study center suggested that greater differences between exercisers and controls were achieved in Edmonton than in Calgary (data not shown). Although women in Edmonton were heavier than women in Calgary, as noted above, baseline adiposity did not modify the effect of the intervention. In addition, the exercise group in Edmonton completed more facility-based sessions per week than exercisers in Calgary (2.7 vs 2.1; P<0.001) and exercised at higher intensity levels (rate of perceived exertion 13.5 vs 11.8; P<0.001).

Greater decreases in adiposity were achieved with a greater mean duration spent at each week exercising (Figure 2). Compared with controls, whose percentage decrease in body fat was 1.3%, the percentage decrease in exercisers with a mean weekly duration <150, 150–225 and ⩾225 min was 2.5%, 8.1 and 11.4%, respectively. An even greater decrease in intra-abdominal fat was seen across these four groups (1.6 vs 10.4 vs 15.0 vs 24.5%).

Using categories suggested for clinical relevance (Table 3),⁴² in this study, weight loss >5% was achieved in 28% (43/152) of the exercisers compared with 14% (21/155) of the controls. Conversely, weight gain (>3%) was seen in 8% (12/152) of the exercisers compared with 12% (19/155) of the controls. The likelihood of clinically relevant weight loss increased with greater duration of exercise.

This yearlong aerobic exercise intervention among postmenopausal women resulted in statistically significant reductions in overall and abdominal adiposity without any intervention to change dietary intake. Furthermore, women in the exercise group, who achieved a higher duration of physical activity, experienced greater average decreases in adiposity. The combination of facility- and home-based program was achievable and resulted in statistically significant increases in physical activity.

Our study differed from previous randomized trials^{1, 15, 16, 18, 19, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56} of exercise interventions among postmenopausal women that were at least 6 months duration and examined adiposity outcomes. It had a large sample size, used quantitative imaging techniques that are preferable for measuring adiposity, had a low drop-out rate, excellent adherence and used a supervised, high volume of exercise. Of these trials, only two studies carried out by Irwin et al. in the United States^{15, 56} and Velthuis et al. in the Netherlands⁴⁷ were sufficiently comparable with ours with respect to study design, exercise volume and outcome measures. Irwin et al.¹⁵ found statistically significant decreases in adiposity of a smaller magnitude than that in our trial and a dose–response with increasing exercise adherence, whereas the trial by Velthuis and colleagues⁵⁶ only found statistically significant decreases for total body fat. The Dose–Response to Exercise in postmenopausal Women trial carried out by Church et al.^{44, 46} was designed to test the effects of three different doses of exercise on cardiorespiratory fitness over a period of 6 months in sedentary postmenopausal, overweight and obese women with elevated blood pressure. These investigators found statistically significant decreases in waist circumference among exercisers, but not in weight or percent body fat, and no dose–response trend was observed.^{44, 46} A statistically significant effect might have been observed given a longer duration; alternatively, the absence of a dose–response trend may be explained by compensatory increases in energy intake that increase as the weekly volume of exercise increases.⁴⁶ In our study, energy intake decreased among controls relative to exercisers, suggesting that at least some compensation by energy intake was made.

In this study and most other exercise studies, weight change is largely accounted for by a loss of fat mass with the preservation of lean mass.^{15, 16, 43, 49} Although the consensus is that overweight or obese subjects will experience greater changes in adiposity than those of normal weight,^{1, 15, 16, 57, 58} in our study, we did not find that baseline BMI modified the effect of the intervention on changes in adiposity, possibly because most women were overweight or obese.

A recent comprehensive review concluded that without caloric restriction, aerobic exercise in the range of 13–26 MET-hours per week results in decreases in abdominal adiposity.¹ This conclusion is supported by our study in which 17 MET-hours per week on average over the intervention year were expended by the exercisers relative to controls. With this volume of exercise, average reductions in intra-abdominal fat and subcutaneous abdominal fat of 17 and 10%, respectively, were achieved. Other studies including postmenopausal women have also observed reductions in abdominal adiposity with aerobic exercise.^{15, 16, 17, 18, 44, 59} In addition, we found larger reductions with longer weekly duration of exercise; women who exercised >225 min per week had nearly 25% reductions in intra-abdominal fat observed. This dose–response relationship is supported by previous randomized and nonrandomized trials (reviewed in Ohkawara et al.⁶⁰), but was not observed in the Dose–Response to Exercise in postmenopausal Women trial.⁴⁴ Our study and others also suggest that intra-abdominal fat may be lost in a higher proportion than overall fat in response to increased energy expenditure, and that intra-abdominal fat may be decreased even in the absence of significant weight loss or after controlling for change in weight.^{15, 16, 46, 58, 61} Even after controlling for percent change in total fat mass, exercisers in the current study still achieved a statistically significant change in intra-abdominal fat relative to controls (data not shown).

Lower adiposity, intertwined with other related mechanisms such as levels of endogenous sex hormones, metabolic hormones, growth factors and immune factors, likely has a role in the association between physical activity and breast cancer.^{62, 63, 64} Abdominal adiposity is etiologically relevant to breast cancer risk;⁶⁵ positive associations with waist–hip ratio, waist circumference or other measures of central adiposity have been found in most studies of postmenopausal breast cancer risk.^{3, 66, 67, 68, 69} It remains to be seen whether adding a dietary intervention component has additive effects on reductions in adiposity, particularly on intra-abdominal adiposity.⁷⁰

The limitations of this study include the lack of compliance amongst controls, as 23% reported >150 min per week of physical activity during the intervention, and the limited generalizability of the sample because of the exclusion criteria, including the presence of comorbid conditions such as diabetes and hypercholesterolemia. A per protocol analysis in which participants in either the exercise or control group achieving <150 min per week were compared with participants in either group achieving ⩾150 min per week indicated that the difference in the weight loss between these groups was almost exactly similar to that between the intervention groups (data not shown). Furthermore, despite instructions not to change dietary energy, 20% of exercisers and 31% of controls decreased their caloric intake >300 kcal per day and 14% of exercisers and 8% of controls increased their caloric intake >300 kcal per day. Although food frequency questionnaires are limited as means of measuring dietary intake, because responses are self-reported and subject to measurement error, we repeated the same measurement at the beginning and end of the trial in both exercisers and controls.

It is of importance to note that this study was designed as an efficacy trial, not an effectiveness study, and future research will evaluate how likely uptake of this level of exercise in postmenopausal women would be and how to develop strategies to enhance adoption and maintenance. Furthermore, the level of exercise that was prescribed for our study population is comparable with that found amongst the highest activity groups in observational studies^{20, 21} and is also within the range of public health recommendations of exercise for chronic disease reduction.¹ Although this study has provided some preliminary evidence on how aerobic exercise can be used to decrease adiposity levels that may be associated with cancer risk, it has not addressed the question of the exact dose and type of activity needed for the optimal reduction in adiposity levels. Our preliminary findings from analyses conducted within the exercise arm of the trial need to be substantiated in a future randomized controlled trial that compares different doses of activity in separate arms of the trial and the consequent effect on adiposity and other metabolic hormones. Finally, we recognize that in clinical practice, a multipronged approach should be used to decrease chronic disease risk including intervening on other modifiable lifestyle risk factors. Results from one observational study suggest that postmenopausal breast cancer risk may be reduced by 10% for every 5 kg of weight lost from a woman's highest body weight attained earlier in life,²⁷ which translates into a risk reduction of 4–5% in our exercise group. Higher risk reductions for breast cancer (and other chronic disease associated with obesity) might be attained using a weight loss strategy that incorporates both physical activity and dietary changes.

In conclusion, this trial has addressed a gap identified in the scientific literature for rigorous and well-designed randomized controlled trials of higher volume, longer duration and exercise interventions that quantify using direct imaging methods the impact of exercise on body composition.³¹ It provides direct empirical evidence that previously sedentary, mostly overweight, postmenopausal women can achieve and sustain high levels of aerobic exercise that result in statistically significant reductions in all measures of adiposity. These levels of change in adiposity through exercise could be beneficial for chronic disease risk reduction.

This study was funded by a research grant ( no. 017468) from the Canadian Breast Cancer Research Alliance. Dr Friedenreich was funded by career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research. Dr Courneya is supported by the Canada Research Chairs Program. The study set up was carried out by Kim van der Hoek and Marla Orenstein, and the Study Coordinators were Rosemary Crosby and Ame-Lia Tamburrini. The Fitness Centre Managers were Ben Wilson, Lisa Workman and Diane Cook. The Exercise Trainers were Shannon Hutchins, Kathy Traptow, Shannon Brown, Susan Daniel, Parissa Gillani, Stephanie Sanden, Karen Mackay and Sandra Olsen. Data preparation and analysis was carried out by Sandra Blitz, Sony Brar and Qinggang Wang.

The authors declare no conflict of interest.