Diet and Sex Hormones in Girls: Findings From a Randomized Controlled Clinical Trial

Background: Results of several studies have suggested that diet during adolescence may influence the risk of breast cancer in adulthood. We evaluated whether an intervention to lower fat intake among adolescent girls altered their serum concentrations of sex hormones that, in adults, are related to breast cancer development. Methods: We conducted an ancillary hormone study among 286 of the 301 girls who participated between 1988 and 1997 in the Dietary Intervention Study in Children, in which healthy, prepubertal, 8- to 10year-olds with elevated low-density lipoprotein cholesterol were randomly assigned to usual care or to a behavioral intervention that promoted a low-fat diet. Median time on the intervention was 7 years. Blood samples collected before randomization and at the year 1, year 3, year 5, and last visits were assayed to determine the girls’ serum levels of sex hormones. All P values are two-sided. Results: At the year 5 visit, girls in the intervention group had 29.8% (95% confidence interval [CI] = 5.4% to 47.9%; P = .02) lower estradiol, 30.2% (95% CI = 7.0% to 47.7%; P = .02) lower nonsex hormone binding globulin-bound estradiol, 20.7% (95% CI = 4.7% to 34.0%; P = .02) lower estrone, and 28.7% (95% CI = 5.1% to 46.5%; P = .02) lower estrone sulfate levels during the follicular phase of the menstrual cycle and 27.2% (95% CI = 5.7% to 53.1%; P = .01) higher testosterone levels during the luteal phase of the menstrual cycle than did girls in the usual care group. At the last visit, the luteal phase progesterone level was 52.9% (95% CI = 20.0% to 72.3%) lower for girls in the intervention group than for girls in the usual care group (P = .007). Conclusion: Modest reductions in fat intake during puberty are associated with changes in sex hormone concentrations that are consistent with alterations in the function of the hypothalamic–pituitary–ovarian axis. Whether these changes influence breast cancer risk is currently unknown. [J Natl Cancer Inst 2003;95:132–41]