Increased Unbound Cortisol in the Plasma of Estrogen-treated Subjects*

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Abstract
Adrenal cortisol production rate was determined in a group of control and estrogen-treated subjects and correlated with the level of protein bound and unbound cortisol in their plasma. Both bound and unbound plasma cortisol levels were found to be appreciably elevated in clinically eucorticoid, estrogen treated subjects, when compared to the control group. Both plasma bound and unbound cortisol levels are a fair index of the adrenal cortisol production rate in the nonestrogen -treated subject but these 2 parameters are relatively elevated in the estrogen-treated subject at equivalent rates of adrenal cortisol production. The proportion of unbound to total plasma cortisol bears a closer relationship to adrenal cortisol production in the combined group of estrogen and nonestrogen treated subjects than does either of these parameters independently. This data is not consistent with the postulate that the unbound level of plasma cortisol, irrespective of what the total level may be, is the deciding factor in determining whether the human subject will show clinical evidence of normal or abnormal tissue cortisol concentration.

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