Adult women with Turner's syndrome are quite short. Several treatments have been used to increase growth rate in these patients. They include oxandrolone (1), growth hormone (2, 3), and low dose estrogen (4). However, the ability of these hormone treatments to increase adult height has never been evaluated in controlled clinical trials. We propose to evaluate the effect on adult height of low dose estrogen, growth hormone, and the combination of low dose estrogen and growth hormone. Patients will be entered into the study from ages 5 to 12 and will be assigned randomly to one of the four groups (the 3 above treatment groups or placebo). The randomized assignment will be double-blind throughout the study. Treatment will be maintained to adult height (the first height measurement at which the preceding annual growth rate was < 1.5 cm). Beginning at age 12, the estrogen treatment in all 4 groups will be changed to a standardized regimen of increasing estrogen dose, so that all children in the study will undergo secondary sexual changes at an appropriate age. In addition, the study will assess the effect of growth hormone and estrogen treatment on bone density and, in a parallel, separate, study, the effect of treatment on cognition and learning ability.
INCLUSION CRITERIA All subjects will be outpatients. Patients must be females with Turner's syndrome diagnosed by leukocyte karyotype Chronologic age greater than or equal to 5 years. Prepubertal Tanner I status. If breast development is Tanner II or III, demonstration of castrate status through measurement of serum FSH (greater than 12 MIU/ML). All patients must be below the 10th percentile for chronologic age. Patients must have at least 6 months accurate, growth measurements available for calculation of pre-study growth velocity. Pretreatment measurements must be obtained during a time when the patient is not receiving a potential growth-promoting agent. Patients judged to be thyroxine deficient must have replacement which has resulted in normal thyroid function tests over the three-month period prior to enrollment (T4, T3, Thyroid Stimulating Hormone). Patients and/or parents or legal guardians of patients must sign an informed consent statement. Assent should be obtained from all patients competent to understand the protocol. Local IRB requirements apply. EXCLUSION CRITERIA Patients who have received any form of human growth hormone within the past 3 months, or who have received a cumulative course of therapy totaling greater than one year. Patients who have received treatment with estrogen or androgen in the past three months or who have received a cumulative course of therapy totaling greater than one year. Patients who have any Y component in their chromosome analysis. Patients with a chronologic age greater than 12 years. Patients with a bone age greater than 12 years. Patients who have clinically significant cardiac, pulmonary, gastrointestinal, hepatic or renal disease or who have had any malignancy. Patients who have significant hematuria or proteinuria in pretherapy evaluation. Patients who have diabetes mellitus. Patients who have any active chronic infection (tuberculosis). Patients who are taking amphetamines or any other drugs known to interfere with growth hormone secretion or actions. Patients who are poor medical, psychological, or psychiatric risks for whom, in the opinion of the principal investigator, the investigational drug would be unwise. Patients whose parents are substance abusers, nor those who come from homes in which appropriate emotional development may be limited. Patients who cannot be seen on the schedule required by the protocol.