Urinary excretion of different corticosteroid-metabolites in oral contraception and pregnancy.

Abstract

ABSTRACT In two groups of patients the urinary excretion of numerous metabolites of cortisol, 11-deoxycortisol (compound S), corticosterone, 17-hydroxyprogesterone and pregnenolone were determined according to a modification of the method of Cost & Vegter (1962). The first group consisted of 7 women with severe primary dysmenorrhoea. Their ages ranged from 17 to 23 years, and all of them received cyclical treatment with a daily dose of 5 mg of 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) + 0.1 mg of 17α-ethynyl-oestradiol-3-methylether (mestranol) until the excretion of total pituitary gonadotrophins was completely suppressed, and the excretion of 17-ketogenic steroids (17-KGS) had decreased to a constant level. This occurred after treatment for 18 to 24 weeks. In all patients the excretion of individual corticosteroid-metabolites was determined before treatment started and again at the end of the treatment period. At the same times the pituitary function was evaluated by means of the metyrapone-test. The second group consisted of 5 normal pregnant women aged 21 to 28. In these women, the excretion of individual corticosteroid-metabolites was determined once during the second trimester of pregnancy. In the first group, the average excretion of allo-tetrahydrocortisol, tetrahydrocortisone, allo-tetrahydrocorticosterone, and pregnanetriol was decreased during treatment, and the decrease in the allo-compounds was significantly greater than the decrease in the other metabolites. The excretion of non-hydrogenated cortisol increased during treatment. Furthermore, the metyrapone-test was found to be normal in all 7 patients both before and during treatment. In the second group, a decrease was found in the excretion of allo-tetrahydrocortisol, allo-tetrahydrocorticosterone, and Δ5-pregnenetriol, while the excretion of Reichstein's substance U, non-hydrogenated cortisol, tetrahydro-11-dehydrocorticosterone, and non-hydrogenated 11-dehydrocorticosterone was increased. The increase observed in non-hydrogenated cortisol, corresponded to the high plasma cortisol levels found in both groups. These changes were ascribed to the oestrogenic component in the preparation administered to the patients in group I, and to the high oestrogen level in the pregnant women (group II). The decrease in the excretion of the 5α-hydrogenated compounds, allo-tetrahydrocortisol and allo-tetrahydrocorticosterone, indicates that there is an inhibition of the 5α-reductase activity in pregnancy as well as during treatment with megestrol acetate + mestranol. However, the data allow of no conclusion as to whether the inhibition is a competitive or non-competitive effect.