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Because the long-term effects of estrogen replacement in adolescents with ovarian failure and hypothalamic amenorrhea have not been previously studied, we conducted a 2-year study of 35 patients to determine factors contributing to baseline bone density measures (bone density, bone mineral content, and bone width) and the response to estrogen therapy. Estrogen-deficient patients were often profoundly osteopenic by single-photon absorptiometry of the radius and dual-photon absorptiometry of the spine, despite estrogen replacement. Variables that were significant predictors of better initial single-photon absorptiometry measurements included increased age, increased body mass index, spontaneous pubertal development, lack of radiation therapy, and lower serum osteocalcin. Patients treated with estrogen/progestin had stable cortical bone mineral content and bone density at the distal one-third of the radius, a slight improvement in bone density at the distal one-tenth of the radius, and an encouraging, but marginal, improvement in the z score (standard deviation from the mean) of bone mineral content at the distal onetenth. The z scores for cortical bone width and bone density decreased, suggesting a possible relative worsening over time. In untreated estrogen-deficient girls, bone mineral content and bone density decreased (but not significantly); the z score of cortical bone width showed a significant decrease. Using dual-photon absorptiometry, a history of radiation therapy was found to be a predictor of lower bone density compared with age-matched controls. Estrogen/ progestin therapy did not result in changes in serum levels of lipids and antithrombin HI, weight, or blood pressure. This study suggests that because most adolescent/young adult patients with estrogen deficiency may not achieve normal bone density with current therapy, earlier and more aggressive intervention may be necessary.

(C) 1990 The American College of Obstetricians and Gynecologists