Effect of Estrogen on Steroid Levels in Plasma and Urine. ∗ †

Alteration of adrenal steroid metabolism by administration of estrogenic substances has received considerable attention. The conflicting results, chiefly in animals, have suggested either direct interference with adrenal steroid synthesis, inhibition or stimulation of ACTH (11,12,4). That different parameters of adrenal function, such as adrenal weight, plasma concentration and excretion of Porter-Silber material, 17 ketosteroids, etc., have been studied in various animals and humans and that both synthetic and natural estrogens were used, may have led to these conflicting interpretations. Administration of comparatively large doses of estrogens appears to induce increased levels of plasma corticoids in the human (13,12). However, most authors are hesitant to correlate this with increase in adrenal function. Differences in protein binding of hydrocortisone and in rate of reduction of the molecule have been presented as more attractive explanations (7,13,10). In agreement with this reasoning, it has been shown that total daily production of hydrocortisone by the adrenal is decreased when estrogen is given (9). The present study investigated the effect of approximately physiological levels of naturally occurring estrogenic material on adrenal steroid levels in plasma and urine, and also to determine ACTH responsiveness under such conditions. Through such experiment, more information could be gathered concerning the relation between ovarian and adrenal activity.

Methods. The subjects were 9 apparently healthy individuals, in third decade of life, 6 males and 3 females. Urine was collected during a 48-hour period and stored in deep freezer until processed. Intravenous ACTH (25 mg) was then administered from 9 to 2 p.m. Blood samples were drawn immediately prior to and following ACTH. Another 24-hour urine pool was collected on day of ACTH infusion, starting at 9 a. In. Subjects were then given 5 mg of estrogen by mouth daily (Premarin 2.5 mg B.I.D.) for 5 days. Urine collections were started again on 3rd day of estrogen periods and on 5th day an ACTH test was carried out, as previously described. The entire experiment was therefore divided into 3 parts.