Sex hormone changes in a 24-mo dietary and physical activity randomized intervention trial in postmenopausal females: the Diet, physical Activity and Mammography study (DAMA) study

Background: The role of sex steroid hormones in the etiology of several diseases, including breast and endometrial cancer, has been widely documented. In postmenopausal females, higher concentrations of estrogens and androgens are associated with a higher risk of developing breast cancer. It is therefore important to investigate whether and how diet and physical activity (PA) can modulate sex hormone blood concentrations. Objectives: We evaluated the effect of a 24-mo dietary and/or PA intervention on plasma concentrations of a series of sex hormones. Methods: The 234 study participants were healthy postmenopausal females aged 50–69 y, with high breast density, nonsmokers, and no hormone replacement therapy users. They were randomly assigned to the following 4 intervention arms: 1) isocaloric dietary intervention, mainly plant-based; 2) moderate-intensity exercise intervention with ≥1 h/wk of supervised strenuous activity; 3) both dietary and exercise interventions; 4) control group with general recommendations on healthy lifestyle. In plasma samples collected at baseline and at the end of the intervention, concentrations of estradiol, estrone, progesterone, 17-OH progesterone, testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were determined by liquid chromatography tandem mass spectrometry methods. Sex hormone-binding globulin was determined by immunoassay, and free estradiol and testosterone were calculated using the Vermeulen method. Statistical analyses were performed using Tobit regression models. Results: After 24 mo, females randomly assigned to dietary treatment (arms 1 + 3) showed significant lower concentrations of estradiol [exp(β) 0.77; 95% confidence interval (CI): 0.61, 0.97; P value 0.03] and free estradiol (exp(β) 0.81; 95% CI: 0.65, 0.998; P value 0.048) compared with the control group (arms 2 + 4). No significant differences emerged for the other sex hormones. No effect of PA intervention was evident. Further adjustment for weight change that occurred during the intervention did not modify the results. Conclusions: Our results suggest that, in healthy postmenopausal females with high breast density, a healthy diet mainly based on plant food may play a role as a modulator of plasma estradiol concentration. This trial was registered at the ISRCTN Registry (www.isrctn.com) as ISRCTN28492718.