Low-dose estrogen therapy significantly increases radioimmunoassayable serum hGH concentrations in the prepubertal hypogonadal female. In this study, we have examined the effects of short- and long-term low-dose ethinyl estradiol therapy on the endogenous production rates and metabolic clearance rates of hGH. We used deconvolution mathematical modeling to provide quantitative estimates of individual secretory parameters and to calculate subject-specific hGH metabolic clearance rates, by using all serum hGH concentrations and their variances considered simultaneously. Nine girls with Turner's syndrome (mean age 7.7 +/- 0.5 y) were studied on three separate nights by drawing blood every 20 min from 2200 to 0800 h before (I), after 1 wk (II), and 5 wk (III) of 100 ng/kg/d ethinyl estradiol therapy orally. We found that the endogenous hGH production rate more than doubled in all patients studied after 5 wk of ethinyl estradiol therapy (194 +/- 22 (I), 290 +/- 43 (II), and 412 +/- 66 (III) micrograms/L/12 h; p less than 0.05 for I and III). The half-life of endogenous hGH was not altered in the estrogen treatment paradigm with a mean of 19 +/- 1.6 min in study I and 18 +/- 1.2 min in both studies II and III. Our results suggest that even prepubertal concentrations of gonadal steroids in the hypogonadal female may be physiologically relevant to the maintenance of normal somatotrope secretory function.