To determine if the mode of 17 beta-estradiol (E(2)) administration affects growth hormone (GH) concentrations, eight postmenopausal women were studied under the following conditions: (1) control tno E(2)), (2) oral E(2) (Estrace, 1 mg every 12 h for 2 weeks) and (3) transdermal E, (Estraderm patch, 0.1 mg, two patches changed daily for 2 weeks). Blood was collected every 5 min for 24 h and assayed for serum GH concentrations using a sensitive chemiluminescence assay, Serum E(2) levels were comparable during both E(2) treatment regimens when measured with a specific chemiluminescence assay. The 24-h integrated GH concentrations (IGHC, min .mu g/L) increased in all eight subjects from (mean +/- SE) 494 +/- 102 during control to 860 +/- 111 (P < 0.05) and 832 +/- 149 (P < 0.05) during oral and transdermal E(2), respectively. Both E(2) treatments significantly increased GH pulse height, individual pulse area, incremental pulse amplitude, interpeak valley concentration, and interpeak valley nadir (as measured by Cluster algorithm) when compared with control. No significant differences were observed in the number of GPI pulses per 24 h. Insulinlike growth factor-I (IGF-I, mu g/L) concentrations decreased from 165 +/- 19 (control) to 109 +/- 11 (oral E(2), P < 0.05) and 122 +/- 15 (transdermal E(2), P < 0.05). No statistically significant differences in attributes of pulsatile GH release or IGF-I concentrations were observed between the oral and transdermal E(2) treatments. We conclude that both oral and transdermal E(2) treatment increase serum GH concentrations in postmenopausal women. This increase is manifested by larger GH pulses and higher basal (interpulse) GH levels, not by changes in pulse frequency. Both routes of E(2) administration decrease serum IGF-I concentrations, which may attenuate IGF-I negative feedback on pituitary somatotrophs and hypothalamic somatostatin secretion, resulting in enhanced pulsatile GH release.