Effect of energy deficiency on estrogen metabolism in premenopausal women

Purpose: Physical activity has been associated with decreased breast cancer risk, potentially through changes in estrogen metabolism. Two-hydroxyestrone (2-OHE1) and 16 alpha-hydroxyestrone (16 alpha-OHE1) have different biological properties, and the ratio of these metabolites (2/16) has been proposed to predict breast cancer risk. Diet and exercise have been found to influence estrogen metabolism, particularly when a state of negative energy balance is achieved. We sought to determine whether 4 months of moderate-intensity exercise coupled with calorie restriction would result in changes in urinary 2-OHE1, 16 alpha-OHE1, or 2/16 in sedentary, premenopausal, eumenorrheic women. Methods: Average age was 31.5 yr, average body fat was 31.6%, and average BMI was 23.7. Urinary estrogen metabolites were measured in 24 women during the baseline and for four intervention months in the midfollicular and midluteal phases. Results: The intervention produced a significant drop in body fat (4.5%) and body weight (3.7 kg). Aerobic fitness increased significantly (26%; P < 0.001). Overall, there were no significant effects of the diet and exercise intervention on 2-OHE1, 16 alpha-OHE1, or 2/16. However, when divided into tertiles according to baseline 2/16, the intervention resulted in significant increases in 2/16 in women in the lowest tertile. Women in the lowest tertile (average 2/16 = 0.91) did not differ from the other tertiles in baseline estradiol concentrations, body fat, weight, fitness, or changes in these variables with the intervention. Conclusion: The data suggest that women at higher risk for developing breast cancer because of low 2/16 may reduce their risk by participating in lifestyle interventions such as exercise/calorie restriction.