Adiposity and Sex Hormones in Girls

Abstract

Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer, but few studies have addressed the relation of adiposity with sex hormones in girls. We prospectively examined associations between adiposity and circulating levels of sex hormones and sex hormone -binding globulin (SHBG) among 286 girls in the Dietary Intervention Study in Children. Participants were 8 to 10 years old at baseline and were followed for an average of 7 years. Anthropometric measurements were taken at baseline and at subsequent annual visits, and blood samples were collected every 2 years. Concentrations of dehydroepiandrosterone sulfate (DHEAS) during follow-up were higher among girls with greater body mass index (BMI) at baseline. The mean for the lowest BMI quartile was 63.0 Mg/dL compared with 78.8 Mg/dL for the highest quartile, and each kg/m 2 increment in baseline BMI was associated with a 4.3% increase (95% confidence interval, 1.6-7.0%) in DHEAS levels during follow-up (P trend = 0.002). Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline. The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile, and each kg/m 2 increment in baseline BMI was associated with an 8.8% decrease (95% confidence interval, 7.0-10.6%) in SHBG levels during follow-up (P trend < 0.0001). Estrogen and progesterone concentrations were similar across BMI quartiles. These findings suggest that adiposity may alter DHEAS and SHBG levels in girls. Whether and how these differences affect breast development and carcinogenesis requires further research. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1880 -8)

Relative Weight at Age 12 and Risk of Postmenopausal Breast Cancer

“…In a 7-year longitudinal study of 286 girls initially ages 8 to 9 years, adiposity was associated with higher circulating concentrations of DHEA sulfate and lower concentrations of sex hormone -binding globulin; however, there were no consistent associations for circulating levels of estrogen or progesterone (34). The lack of an association for estrogen would suggest that early adolescent obesity is not likely to influence postmenopausal breast cancer risk through estrogen signaling, consistent with the similar association for ER+ (RR, 0.80) and ERÀ (RR, 0.77) tumors in our study.…”

“…However, the effect of fewer ovulatory cycles could be more pronounced during the time frame before first full-term pregnancy, and particularly in adolescence, due to the greater susceptibility to carcinogens of undifferentiated breast tissue (39,40). There may also be other aspects of the hormonal milieu associated with obesity in the early teenage years that protects against breast cancer, and this requires further evaluation (34,35). Figure 1.…”

Measured adolescent body mass index and adult breast cancer in a cohort of 951,480 women

“…Hormonal pathways were suggested as a potential explanation. Childhood and adolescent obesity in girls was found to be associated with increased levels of androgens [28], which may inhibit the maturation of ovarian follicles and reduce the frequency of ovulatory cycles [28]. Anovulation is indeed more common in overweight/obese fertile women [29]; even a BMI of 24 kg/m 2 is associated with higher risk for ovulatory infertility [30,31].…”

Early menarche is associated with increased risk of asthma: Prospective population-based study of twins

“…Some have argued that the association between asthma and overweight could be attributable to less physical activity in women with high BMI, but studies have shown that the association between asthma and obesity is independent of physical activity [23,24] and that obese women with early menarche may have a more severe asthma phenotype [25]. Higher BMI is also associated with higher levels of female sex hormones [26] and systemic inflammation [27]. Leptin, a pro-inflammatory cytokine secreted by adipocytes, is associated with both early menarche [28] and asthma [29].…”