Effect of estrogen administration on plasma cortisol fractions in normal and panhypopituitary females

The administration of high doses of the synthetic estrogen, ethinyl estradiol (2 mg/day) for 12 days, in five normal females (in the follicular phase of the cycle) and in five patients with panhypopituitarism (Sheehan's disease) kept on thyroid and oral cortisol (20 mg/day), produced a prompt and significant increase in total nonconjugated plasma cortisol (17-hydroxycorticosteroids) and its protein- and nonprotein-bound fractions. These studies suggest that estrogen-induced elevation of nonprotein-bound cortisol (active fraction) is maintained in patients with normal hypothalamic-pituitary-adrenal axis through reversal, partially at least, of the expected inhibition of ACTH release, probably by resetting of the negative-feedback mechanism.