Abstract

Estrogens induce cellular proliferation and are associated with an increased risk of breast cancer. Birth weight and adult body weight have independently been associated with both estrogen levels and breast cancer risk. Thus, we hypothesize that low birth weight, in combination with adult overweight, may influence premenopausal 17beta-estradiol over an entire menstrual cycle of possible importance for breast cancer. Among 204 healthy women, aged 25-35 years, who participated in the Norwegian EBBA-I Study, birth weight and age at menarche were assessed. Levels of 17beta-estradiol were measured in daily saliva samples over one menstrual cycle using radioimmunoassay (RIA). Measurements of body composition; waist circumference (cm), body mass index (BMI, kg/m(2)), and total fat percentage (DEXA, %) were assessed. Fasting blood samples were drawn, and serum concentrations of lipids and hormones were determined. The participating women had mean birth weight of 3,389 g and age at menarche 13.1 years. Women within the highest tertile of birth weight had the lowest 17beta-estradiol throughout the menstrual cycle (p = 0.03), and they tended to have a later age at menarche (p = 0.06). When we looked into birth weight in combination with adult-attained weight, we found that women with lower birth weights, combined with excess weight during adulthood, had higher levels of free 17beta-estradiol over an entire menstrual cycle compared with women with high birth weights and adult overweight. Women with birth weights <3,530 g, who later developed excess body weight (waist >or= 84 cm), showed 33% higher 17beta-estradiol concentrations over a menstrual cycle compared with women with higher birth weights (>or=3,530 g) and adult excess body weight (p = 0.03). The association was even more pronounced in women with birth weights <3,220 g, early age at menarche (<12 years), and adult overweight. Our findings support variation of premenopausal levels of 17beta-estradiol in response to birth weight and energy status in adult life, suggesting that women with low birth weight in combination with adult overweight are put at risk for higher estradiol levels throughout menstrual cycles, which is of possible importance for breast cancer risk.

Highlights

  • Several studies have observed a strong relationship between birth weight and later risk of chronic diseases, indicating that fetal conditions may influence later susceptibility to adult disease (‘Forsdahl- Barker hypothesis’) (1), (2), (3)

  • When we looked into birth weight in combination with adult attained weight, we found that women with lower birth weights, combined with excess weight during adulthood, had higher levels of free 17!-estradiol over an entire menstrual cycle compared with women with high birth weights and adult overweight

  • We studied the average 17!-estradiol by cycle day over the entire menstrual cycle across birth weight tertiles

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Summary

Introduction

Several studies have observed a strong relationship between birth weight and later risk of chronic diseases, indicating that fetal conditions may influence later susceptibility to adult disease (‘Forsdahl- Barker hypothesis’) (1), (2), (3). We hypothesize that low birth weight, in combination with adult overweight, may influence premenopausal hormonal levels over an entire menstrual cycle. Women with birth weights < 3530 g, who later developed excess body weight (waist " 84 cm), showed 33% higher 17!-estradiol concentrations over a menstrual cycle compared with women with higher birth weights (" 3530 g) and adult excess body weight (p = 0.03). The association was even more pronounced in women with birth weights < 3220 g, early age at menarche (< 12 years) and adult overweight. Conclusion: Our findings support variation of premenopausal levels of 17!-estradiol in response to birth weight and energy status in adult life, suggesting that women with low birth weight in combination with adult overweight are put at risk for higher estradiol levels throughout menstrual cycles, of possible importance for breast cancer risk

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