Ultrasensitive estrogen levels at 7 years of age predict earlier thelarche: evidence from girls of the growth and obesity Chilean cohort

Abstract

Objective: Prepubertal estradiol equivalents have been inconsistently linked to age at thelarche; elucidating this relationship becomes relevant given the worldwide decline in the age of puberty onset. Thus, our aim is to assess whether prepubertal girls with higher serum levels of estradiol equivalents at age 7 have a greater risk of presenting early thelarche (ET). Design: Nested case-control study within the Growth and Obesity Cohort Study of 1196 low-middle income children (w50% girls) from Santiago, Chile. Girls were defined as cases (ET; nZ61) if breast bud appeared prior to 8 years of age; controls (nZ91) had thelarche O8 years. Methods: At 6.7 years, weight, height and waist circumference were measured and a fasting blood sample was obtained for measuring estrogen equivalent (ultrasensitive recombinant cell bioassay), DHEAS, leptin, insulin and IGF1. Beginning at 7 years old, Tanner staging was assessed prospectively twice a year and the appearance of breast bud was assessed by palpation. Results: Mean serum estradiol-equivalent at 6.7 years was 3.9G3.6 pg/ml for cases and 3.6G2.3 pg/ml for controls. Girls with ET had a higher risk of presenting elevated estradiol-equivalent (R5 pg/ml) at 7 years (ORZ2.05, 95% CI: 0.96-4.36) than controls that was borderline significant. However, after adjusting by BMI, insulin and IGF1 at age 7, the association between estradiol-equivalent and ET was significant (ORZ2.29 (95% CI: 1.05-5.01)). Conclusions: Chilean girls from low to middle socioeconomic status with ET exhibited double the risk of having high levels of estradiol-equivalent at 7 years than girls with a later age of thelarche. Whole-body adiposity and increased adrenal activity did not explain the observed prepubertal estrogen increase.

High DHEAS Is Associated With Earlier Pubertal Events in Girls But Not in Boys

“…In a recent paper on the effect of obesity in puberty onset [ 12 ], there was a lack of association between adiposity and ovarian volume in girls, suggesting that the advanced breast development observed among early pubertal obese girls may be primarily due to peripheral conversion of relatively inactive androgens to more bioactive estrogens by aromatase in adipose tissues. We recently published that higher levels of estradiol equivalents in prepubertal girls were associated with an earlier thelarche, which remained significant after adjusting for BMI or other adiposity markers, suggesting that these associations were not mediated through adiposity [ 24 ]. These observations are also supported by evidence suggesting that age at the gonadotropin and sex steroid surges have not changed in population studies where age at thelarche has declined [ 25 ].…”

Estrogenic activity of biological samples as a biomarker

“…This suggested that some patients may be affected by this condition due to prenatal/postnatal EDC exposure. The third study (Pereira et al 2015) investigated the relationship between estrogen levels and risk of premature thelarche, assessing the estrogen levels of prepubertal girls aged 7, who were monitored during the following years for the onset of thelarche. The results showed that girls with estrogen levels over 5 pg/ml at 7 years had an increased risk of presenting earlier thelarche onset.…”

Prepubertal and Pubertal Endocrine-Disrupting Chemical Exposure and Breast Density among Chilean Adolescents

“…Higher estrogenic activity in childhood has previously been associated with early breast development in the GOCS cohort (60). Given these prior findings were independent of central activation or peripheral estrogen conversion associated with obesity, it was postulated that this estrogenic activity may reflect EDC action (60). This study suggests that the developing breast tissue of Latina girls is responsive to exogenous hormones during childhood and adolescence.…”