Abstract
IntroductionPhysical inactivity and overweight are risk factors for postmenopausal breast cancer. The effect of physical activity may be partially mediated by concordant weight loss. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise.MethodsOverweight, insufficiently active women were randomised to a diet (N = 97), mainly exercise (N = 98) or control group (N = 48). The goal of both interventions was to achieve 5–6 kg of weight loss by following a calorie-restricted diet or an intensive exercise programme combined with only a small caloric restriction. Primary outcomes after 16 weeks were serum sex hormones and sex hormone-binding globulin (SHBG). Body fat and lean mass were measured by dual-energy X-ray absorptiometry.ResultsBoth the diet (−4.9 kg) and mainly exercise (−5.5 kg) groups achieved the target weight loss. Loss of body fat was significantly greater with exercise versus diet (difference −1.4 kg, P < 0.001). In the mainly exercise arm, the reduction in free testosterone was statistically significantly greater than that of the diet arm (treatment effect ratio [TER] 0.92, P = 0.043), and the results were suggestive of a difference for androstenedione (TER 0.90, P = 0.064) and SHBG (TER 1.05, P = 0.070). Compared with the control arm, beneficial effects were seen with both interventions, diet and mainly exercise, respectively, on oestradiol (TER 0.86, P = 0.025; TER 0.83, P = 0.007), free oestradiol (TER 0.80, P = 0.002; TER 0.77, P < 0.001), SHBG (TER 1.14; TER 1.21, both P < 0.001) and free testosterone (TER 0.91, P = 0.069; TER = 0.84, P = 0.001). After adjustment for changes in body fat, intervention effects attenuated or disappeared.ConclusionsWeight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk. Weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones. The greater fat loss likely explains the observed larger effects on sex hormones.Trial registrationClinicalTrials.gov identifier: NCT01511276. Registered on 12 January 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0633-9) contains supplementary material, which is available to authorized users.
Highlights
Physical inactivity and overweight are risk factors for postmenopausal breast cancer
Significantly larger effects were found for free testosterone (TER 0.92, 95 % Confidence interval (CI) 0.85–0.99), and borderline statistically significant effects were seen for androstenedione (TER 0.90, 95 % CI 0.80–1.01) and sex hormone-binding globulin (SHBG) (TER 1.05, 95 % CI 1.00– 1.12) (Table 4). When we compared both intervention groups with the control group, our secondary comparison, we found that all hormone levels had decreased and SHBG had increased, except for testosterone in the diet group (Table 4)
We found that, in postmenopausal women, 6–7 % weight loss induced mainly by exercise resulted in a more favourable body composition, better physical fitness and larger effects on free testosterone, as well as suggestive effects for androstenedione and SHBG compared with a similar amount of weight loss induced by following a hypocaloric diet only
Summary
Physical inactivity and overweight are risk factors for postmenopausal breast cancer. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise. Obesity and physical inactivity are convincing risk factors for postmenopausal breast cancer, according to the World Cancer Research Fund [1]. Together, these factors contribute to approximately 15 % of breast cancer cases that develop after menopause [2,3,4]. Observational, prospective studies have consistently shown a higher breast cancer risk of up to twofold in postmenopausal women with endogenous sex hormone levels in the highest versus the lowest quintile [6, 7]
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