Estrogen deficiency in adolescents and young adults: impact on bone mineral content and effects of estrogen replacement therapy. 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 on encouraging, but marginal, improvement in the z score (standard deviation from the mean) of bone mineral content at the distal one-tenth. 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 III, weight, or blood pressure. 