Context:The long-term effects of pure 17␤-estradiol (E 2 ) depending on route of administration have not been well characterized.Objective: Our objective was to assess metabolic effects of oral vs transdermal (TD) 17␤-E 2 replacement using estrogen concentration-based dosing in girls with Turner syndrome (TS).Patients: Forty girls with TS, mean age 16.7 Ϯ 1.7 years, were recruited.Design: Subjects were randomized to 17␤-E 2 orally or TD. Doses were titrated using mean E 2 concentrations of normally menstruating girls as therapeutic target. E 2 , estrone (E 1 ), and E 1 sulfate (E 1 S) were measured by liquid chromatography tandem mass spectrometry and a recombinant cell bioassay; metabolites were measured, and dual-energy x-ray absorptiometry scan and indirect calorimetry were performed.Main Outcome: Changes in body composition and lipid oxidation were evaluated.Results: E 2 concentrations were titrated to normal range in both groups; mean oral dose was 2 mg, and TD dose was 0.1 mg. After 6 and 12 months, fat-free mass and percent fat mass, bone mineral density accrual, lipid oxidation, and resting energy expenditure rates were similar between groups. IGF-1 concentrations were lower on oral 17␤-E 2 , but suppression of gonadotropins was comparable with no significant changes in lipids, glucose, osteocalcin, or highly sensitive C-reactive protein between groups. However, E 1 , E 1 S, SHBG, and bioestrogen concentrations were significantly higher in the oral group.Conclusions: When E 2 concentrations are titrated to the normal range, the route of delivery of 17␤-E 2 does not affect differentially body composition, lipid oxidation, and lipid concentrations in hypogonadal girls with TS. However, total estrogen exposure (E 1 , E 1 S, and total bioestrogen) is significantly higher after oral 17␤-E 2 . TD 17␤-E 2 results in a more physiological estrogen milieu than oral 17␤-E 2 administration in girls with TS. (J Clin Endocrinol Metab 98: 2716 -2724, 2013) E strogen is indispensable for normal physiological function in females including breast development and feminization, the growth and differentiation of primary sex organs, skeletal maturation, consolidation, and growth. Although a variety of types of estrogen can achieve full feminization in hypogonadal females, it re-

These data suggest that patients with DM1 have differences in ovarian steroidogenic response to leuprolide, compared with C girls during puberty. Future studies in young women should clarify whether these findings are related to the pathogenesis of hyperandrogenism later in life.

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Pubertal development in girls with T1DM occurred earlier than described in historical cohorts, but a later onset of menarche and final stages of breast development were observed. The increase in BMI-SDS and the stability of WHR in girls with T1DM during puberty suggest that this period may be critical for determining later weight gain and body composition in adult women with this condition.

Background Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited. Methods This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed). Detailed alcohol consumption data were collected during the pregnancy. Children were evaluated up to 8.5 years of age by clinicians masked to exposure status. Results One or more functional central nervous system abnormalities were present in 44.0% (22/50) of the exposed children compared to 13.6% (6/44) of the unexposed (p = 0.002). Growth restriction was present in 27.2% (25/92) of the exposed and 12.5% (12/96) of the unexposed (p = 0.02). Abnormal facial features were present in 17.3% (14/81) of the exposed children compared to 1.1% (1/89) of the unexposed children (p = 0.0002) by direct examination. Of the 59 exposed children with data available to detect at least 1 abnormality, 12 (20.3%) had no abnormalities. Binge drinking from conception to recognition of pregnancy (OR = 1.48 per day, 95% CI: 1.15 to 1.91, p = 0.002) and after recognition of pregnancy (OR= 1.41 per day, 95% CI: 1.01 to 1.95, p = 0.04) and total number of drinks consumed per week from conception to recognition of pregnancy (OR = 1.02 per drink, 95% CI: 1.01 to 1.04, p = 0.0009) were significantly associated with abnormal child outcome. Conclusions After exposure to heavy alcohol consumption during pregnancy, 80% of children had 1 or more abnormalities associated with alcohol exposure. Patterns of alcohol use that posed the greatest risk of adverse outcomes were binge drinking and high total weekly intake. Functional neurologic impairment occurred most frequently and may be the only sign to alert physicians to prenatal alcohol exposure.