Estrogen therapy in Turner's syndrome.

Girls with Turner's syndrome are born short, grow slowly, and usually fail to enter puberty spontaneously and to undergo a pubertal growth spurt. The goal of estrogen therapy is to correct estrogen deficiency in a manner that optimizes height potential, permits attainment of normal bone mass, and provides appropriate feminization with minimal risk of adverse effects. The issues to be resolved include the age at which treatment should be begun, the preparation, route of administration, and dosage to be given, the effect on concurrent growth hormone administration, the rate of dose increase during treatment, the timing and nature of progestin administration, and the total duration of treatment. The available data suggest that treatment should be initiated between the ages of 12 and 14 years. The dose-response relationship between growth rate and estrogen dose is biphasic. Optimal growth stimulation for ethinyl estradiol occurs at approximately 100 ng/kg body weight per day, which is below the dose that produces full feminization. Although suboptimal doses of estrogen and growth hormone appear to have additive effects, estrogen causes only a minor increase in the short-term growth response to an optimal dose of growth hormone. The long-term effects of estrogen combined with growth hormone are unknown. In the absence of data concerning the outcome of different dose schedules, we treated for 2 years at 100 ng/kg/day of ethinyl estradiol, then double the dose annually until menstruation, at which time cyclic monthly progestin therapy is added (medroxyprogesterone acetate 10 mg daily from days 16 to 25). The importance of estrogen in maintaining normal bone mass suggests that treatment should be lifelong. Current research in our clinic is assessing the long-term effect on adult height of ultra-low-dose treatment (25 to 50 ng/kg/day of ethinyl estradiol) during the childhood years (ages 5 to 11), alone or in conjunction with supplemental growth hormone.