Waist-to-Hip Ratio, Body Mass Index and Sex Hormone Levels Associated with Breast Cancer Risk in Premenopausal Caucasian Women

Abstract

Obese women and women with upper body fat distribution have been shown to have a hormonal profile associated with increased risk of breast cancer. This study examines the relationships between obesity and body fat distribution, and sex hormones. Data from 47 healthy nulliparous premenopausal Caucasian women were collected cross-sectionally. Eight were obese and 39 non-obese. Thirteen had normal body fat (NBF), while 34 lower body fat (LBF) phenotypes. The concentrations of serum estrone, estrone sulfate, estradiol, free estradiol (Free E2), %Free E2, androstenedione, testosterone, free testosterone (Free T), %Free T, prolactin and sex hormone-binding globulin (SHBG) levels were determined in the mid-follicular phase. Results showed that in multivariate regression analyses controlling for age, age at menarche and body mass index (BMI), a 0.1 unit increase in waist-to-hip circumference ratio (WHR) towards the normal range decreased %FreeT by 18% (p=0.03), %FreeE2 by 15% (p=0.07) and increased SHBG by 36% (p=0.07). In similar analyses controlling for WHR, a unit increase in BMI increased %FreeE2 by 0.25%(p=0.04), %FreeT by 0.23% (p=0.07), and decreased that SHBG by 0.52% (p=0.07). Multivariate comparison showed SHBG levels to be higher by 39% (p=0.02) and %FreeE2 lower by 13% (p=0.07) in NBF compared to LBF phenotype women. Multivariate comparison between obese and nonobese women, however, showed SHBG levels to be lower by 24% (p=0.04), and %FreeE2 higher by 18% (p=0.04) in obese women. Results suggested that obesity and increasing BMI are associated with a serum sex hormone profile that increases breast cancer risk; however, increasing WHR towards the normal range is not associated with a high risk sex hormone profile. WHR in the normal range appears to be associated with a sex hormone profile that is more protective compared to the lower range.