Adult patients with growth hormone (GH) deficiency require long-term treatment with GH to support normal physiological functioning. For many female patients, endogenous estrogen levels have a considerable impact on the dosing requirements for GH. Estrogen appears to stimulate GH secretion by decreasing liver secretion of insulin-like growth factor-I (IGF-I), resulting in stimulation of the pituitary to synthesize and secrete GH. Oral estrogen results in a higher concentration of liver estrogen than transdermal administration of estrogen. The appropriate dose of GH needs to be determined for each patient based on his or her age, sex, concomitant estrogen therapy, IGF-I level, and short- and long-term response to therapy. Clinical endocrinologists are in the best position to put all these variables into a successful therapeutic scenario.