Using stable tracers of calcium, we have previously shown a significant increase in calcium absorption and retention in prepubertal boys treated with exogenous testosterone. To investigate the effects of estrogen replacement on measures of calcium absorption, retention, and bone turnover, we studied a group of seven hypogonadal girls with Turner's syndrome (mean +/- SE age, 12.5 +/- 0.7 years). At baseline, Ca-42 intravenously (IV) and Ca-44 orally were administered, and blood and urine samples were collected for approximately 130 hours. Estrogen therapy was begun as ethinyl estradiol (4 or 20 mu g/d) or intramuscular depot estradiol given over 4 weeks, after which an identical study was repeated. Analysis of calcium enrichment in blood and urine was performed using mass spectrometry methods. After estrogen therapy, there was a significant increase in calcium absorption ([Va] P = .03) and total calcium retention ([Vbal] P = .04), similar to the effects of testosterone in boys. Bone accretion (Vo(+)) decreased after estrogen therapy (P = .004), as did resorption ([Vo(-)] P = .004). The overall rate of whole-body calcium turnover (Vt) was significantly decreased after estrogen administration (P = .04). These findings were opposite of those observed in prepubertal boys treated with testosterone. The contribution of bone resorption to whole-body turnover (E) also decreased after estrogen therapy (P = .05). These changes were associated with increased levels of 1,25-dihydroxyvitamin D after therapy with estrogens (P = .05). We conclude that estrogen supplementation is significantly anabolic for calcium metabolism by markedly increasing calcium absorption and retention and diminishing the estimated whole-body calcium turnover in girls with severe hypogonadism and Turner's syndrome. Further studies assessing the dietary calcium and/or vitamin D intake and bone mineral density of hypogonadal girls whose estrogen replacement is intentionally delayed will further define the need for calcium or vitamin D supplements in the peripubertal years in this condition. Copyright (C) 1997 by W.B. Saunders Company.