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A. WAYNE MEIKLE, WILLIAM JUBIZ, SHIGERU MATSUKURA, GENGO HARADA, CHARLES D. WEST, FRANK H. TYLER, Effect of Estrogen on the Metabolism of Metyrapone and Release of ACTH, The Journal of Clinical Endocrinology & Metabolism, Volume 30, Issue 2, 1 February 1970, Pages 259–263, https://doi.org/10.1210/jcem-30-2-259
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Abstract
The effect of estrogen on the metyrapone test and the release of ACTH was investigated in normal females on oral sequential contraceptives. Subnormal urinary 17-OHCS and plasma ACTH responses to the oral regular metyrapone dose (750 mg q 4 hr×6) were observed. Responses to a double metyrapone dose (750 mg q 2 hr×12) were normal. Plasma deoxycortisol levels were higher than normal in response to both doses, presumably as a result of the increase in corticosteroid binding globulin. On the regular dose, plasma levels of unconjugated metyrapone were lower and conjugated levels higher than normal. On the double dose, unconjugated metyrapone levels were similar to those observed in normals on the regular dose. Our results suggest that estrogen therapy causes an acceleration of the hepatic conjugation of metyrapone, resulting in lower levels of unconjugated metyrapone in blood, less 11β-hydroxylase inhibition and subnormal ACTH rise.