The Secretion and Metabolism of Cortisol and Aldosterone in Normal and in Steroid-Treated Women*

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Abstract
The secretion rate and the pattern of metabolism of cortisol and of aldosterone were studied in women receiving oral doses of Enovid, norethynodrel, ethynylestradiol 3-methyl ether (EE3ME) and progesterone. Enovid, norethynodrel and EE3ME each had a marked estrogenic effect on the metabolism of cortisol, namely, a raised plasma level and increased plasma protein binding of the hormone, with a decreased excretion of tetrahydrocortisone, tetrahydrocortisol and allotetrahydrocortisol. No change was observed in the relative amounts of these three metabolites excreted. The secretion rate of cortisol was significantly decreased in the subjects receiving Enovid, norethynodrel and EE3ME. Cortisol secretion and metabolism in subjects receiving progesterone was similar to that in control subjects, except for a small but significant increase in the excretion of unconjugated metabolites. Progesterone, Enovid, norethynodrel, and EE3ME in the higher dosage of 0.3 mg per day increased the secretion rate of aldosterone, indicating that both estrogen and progestogen can have this effect. Progesterone treatment did not alter the pattern of metabolism of aldosterone. Both Enovid and EE3ME reduced the percentage of injected aldosterone excreted as glucuronide but had little effect on the percentage excreted as the pH 1-labile conjugate of the hormone. The effect on glucuronide excretion may have been due in part to the increased plasma protein binding of aldosterone caused by Enovid and by EE3ME. It is concluded that the effects of Enovid and of norethynodrel on cortisol metabolism are due to their estrogenic potency. These steroids exert an effect on aldosterone metabolism which may be interpreted as a combination of their estrogenic action with an effect resembling that of progesterone.

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