THE INFLUENCE OF ESTROGEN ON THE SECRETION, DISPOSITION AND BIOLOGIC ACTIVITY OF CORTISOL*

The following findings were obtained which bear on the mechanisms concerned in the rise of plasma free 17-hydroxycorticoid (17-OHCS) levels in patients treated with estrogenic hormone (ethinyl estradiol or diethylstilbestrol): 1) Cortisol accounted for approximately 80 per cent of the plasma free 17-OHCS in a normal subject given estrogen. 2) In patients treated with estrogenic hormone there was a marked rise in the level of plasma free 17-OHCS but no increase in urinary total 17-OHCS excretion. 3) In a man with intact adrenals who received ACTH intravenously and in an Addisonian woman who received cortisol intravenously there was a greater rise in the level of plasma free 17-OHCS and urinary F + E but a lesser rise in urinary THF+THE when estrogen was also administered. 4) On three occasions when patients with adrenal insufficiency were given cortisol intravenously, estrogen produced a diminished rate of removal of free 17-OHCS from plasma and a smaller distribution volume of the injected F. 5) The pituitary glands of 3 patients who had been receiving long-term estrogen therapy showed no Crooke's changes in the basophil cells. It is concluded that the rise in the level of plasma cortisol in patients receiving estrogen is due mainly to a diminished transformation of compound F to certain metabolites and to a greater retention of the hormone within the intravascular or possibly the extracellular fluid compartment. The failure of patients treated with estrogens to show evidence of an excess of cortisol is believed to be due in part to a failure of tissue levels of F to rise to the same degree as the plasma level of the hormone.