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Ana Pereira, Camila Corvalán, Ricardo Uauy, Karen O Klein and Verónica Mericq

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 (∼50% girls) from Santiago, Chile. Girls were defined as cases (ET; n=61) if breast bud appeared prior to 8 years of age; controls (n=91) had thelarche >8 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 3.9±3.6 pg/ml for cases and 3.6±2.3 pg/ml for controls. Girls with ET had a higher risk of presenting elevated estradiol-equivalent (≥5 pg/ml) at 7 years (OR=2.05, 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 (OR=2.29 (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.

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Claus H Gravholt, Niels H Andersen, Gerard S Conway, Olaf M Dekkers, Mitchell E Geffner, Karen O Klein, Angela E Lin, Nelly Mauras, Charmian A Quigley, Karen Rubin, David E Sandberg, Theo C J Sas, Michael Silberbach, Viveca Söderström-Anttila, Kirstine Stochholm, Janielle A van Alfen-van derVelden, Joachim Woelfle, Philippe F Backeljauw and On behalf of the International Turner Syndrome Consensus Group

Turner syndrome affects 25–50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and the Endocrine Society. Advocacy groups appointed representatives who participated in pre-meeting discussions and in the consensus meeting.