Adolescent endogenous sex hormones and breast density in early adulthood.

INTRODUCTION: During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer. METHODS: Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25-29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997. They had sex hormones and sex hormone-binding globulin (SHBG) measured in serum collected on one to five occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV. RESULTS: Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all P trend ≤0.03) but not when measured in postmenarche samples (all P trend ≥0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 %, respectively. Estrogens, progesterone, androstenedione, and testosterone in pre- or postmenarche serum samples were not associated with %DBV (all P trend ≥0.16). CONCLUSIONS: Our results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher %DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999.

Diet and sex hormones in boys: findings from the dietary intervention study in children.

CONTEXT: Diet reportedly alters serum sex hormone concentrations in adults, but little is known about the influence of diet during puberty on these hormones. OBJECTIVE: We aimed to determine whether an intervention to lower fat intake during adolescence alters serum sex hormone concentrations and progression through puberty. DESIGN: In 1990-1997, we conducted an ancillary study to the Dietary Intervention Study in Children, a multicenter, randomized, controlled clinical trial to test the safety and efficacy of a cholesterol-lowering dietary intervention in children. PARTICIPANTS: Healthy, prepubertal, 8 to 10 yr olds with elevated low-density lipoprotein cholesterol were randomized to usual care or a behavioral intervention. Of 362 randomized Dietary Intervention Study in Children boys, 354 participated in the ancillary study. Eighty-four percent of boys attended last visits when their median time on trial was 7.1 yr. INTERVENTION: The behavioral intervention continued throughout the duration of the trial and promoted a diet with 28% energy from total fat, less than 8% from saturated fat, 9% or less from polyunsaturated fat, and less than 75 mg cholesterol per 1000 kcal. OUTCOME MEASURES: The main outcome measure for boys formulated before study initiation was non-SHBG bound testosterone concentration. Secondary outcomes included serum total testosterone, dihydrotestosterone, androstenedione, estradiol, estrone, SHBG, and Tanner stage. RESULTS: There were no significant treatment group differences in boys' serum hormone levels, SHBG, or Tanner stages at any individual visit or over the course of the trial when evaluated by longitudinal models. CONCLUSION: Modest reductions in total fat, saturated fat, and possibly energy intake do not alter progression through puberty or serum sex hormone concentrations in adolescent boys.

Validity of estimating non-sex hormone-binding globulin bound testosterone and oestradiol from total hormone measurements in boys and girls.

BACKGROUND: Circulating levels of bioavailable oestradiol and testosterone are often desirable for clinical practice or investigational studies of children. However, assays to measure circulating hormone levels might not always be accessible. We sought to validate the empirical calculation of circulating bioavailable testosterone and oestradiol in children. METHODS: Six hundred and sixty-three eight- to 10-year olds were recruited to the Dietary Intervention Study in Children (DISC). DISC was a randomized clinical trial designed to test efficacy of a dietary intervention to reduce serum cholesterol (LDL-C) in children with elevated cholesterol. Assay measures of oestradiol, testosterone, sex hormone-binding globulin concentration (SHBG) and albumin concentration in girls as well as dihydrotestosterone in boys were measured for up to 10 y. We calculated measures of circulating non-SHBG bound oestradiol and testosterone from total hormone levels using the law of mass action. We compared proportional differences in assay measured minus calculated non-SHBG bound hormone levels versus their averages using generalized estimating equations-estimated linear regressions. RESULTS: On average, calculated values overestimated assay measured values (-11.7% for non-SHBG bound oestradiol in girls and -2.6% for non-SHBG bound testosterone in boys). The intercept and slope of the regression for non-SHBG bound oestradiol in girls were -0.13 (95% confidence interval [CI] -0.14 to -0.12) and 0.005 (95% CI 0.003-0.007), respectively. The intercept and slope for non-SHBG bound testosterone in boys were -0.16 (95% CI -0.17 to -0.14) and 0.0006 (95% CI 0.0005-0.0006). CONCLUSION: While calculated values might be useful for research purposes, they are generally not close enough for clinical purposes.