PITUITARY-ADRENAL FUNCTION IN ORAL CONTRACEPTION

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Abstract
Fourteen normally menstruating women aged 17 to 29 were treated cyclically with a daily dose of 5 mg of 6-methyl-6-dehydro-17[alpha]-acetoxyprogesterone (megestrol acetate) + 0.1 mg of 17[alpha]-ethynyl-estradiol-3-methylether (mestranol) for a period of 3 to 74 weeks. During treatment a gradual decrease in the excretion of both 17-ketogenic steroids (17-KGS) and 17-ketosteroids (17-KS) was found. After cessation of treatment, a rapid increase to pretreatment levels in the excretion of both 17-KGS and 17-KS was found. The decrease in the output of 17-KGS and 17-KS observed during treatment with megestrol acetate + mestranol might be explained by a suppression of the pituitary function, a suppression of the adrenal cortical function and a change in the metabolism of the corticosteroids. The purpose of the present investigation was to explore these hypotheses. 8 patients were treated with the above mentioned dose of megestrol acetate + mestranol until the excretion of pituitary gonado-trophins was significantly suppressed. This occurred after a treatment-period of 3 to 10 months. In all 8 patients we determined the responsive to metyrapone before the treatment started and a short time before the treatment was discontinued. During treatment all 8 patients showed a normal response to oral administration of metyrapone. Furthermore, in 6 out of the 8 patients we tested the response of the adrenal cortex to intravenous and intramuscular administration of corticotrophin (ACTH) just before the treatment was discontinued. In all patients a normal ACTH-stimulation test was found. During treatment, the concentration of plasma cortisol was significantly increased to values about 3 times the control values, whereas the concentration of plasma 11-deoxycortisol (compound S) remained unchanged. This high plasma cortisol level during treatment is probably caused by an increased protein-binding of cortisol. As both the responsive to methyrapone and to ACTH is normal during treatment with megestrol acetate + mestranol, we are of the opinion that the decrease observed in the excretion of 17-KGS and 17-KS is due to a change in the metabolism of the corticosteroids.