Pituitary-adrenocortical function of women following Gestagen administration

Abstract

Investigation on the effect of Gestagens on the Pituitary-Adrenocortical function has been undertaken in women who have received long-term administration.The studies were made in two groups of women : (1) The one group was orally administered Gestagens, i.e., a compound of Norethindrone-Mestranol (norethindrone 5 mg., with mestranol 0.05 mg. per tablet), for a cyclic period of eight to twelve months. (2) While, to study the effect of larger dosage administration, the other group received Norethindrone-Mestranol for a period of three months in connection with pseudopregnancy. The following conclusions were obtained based on various endocrinological findings : 1. No precise conclusion could be drawn from the findings of urinary 17-OHCS, 17-KS evaluations and Thorn test.2. It was found, however, that there were significant decreases of urinary 17-OHCS, 17-KS, Pregnane-diol and Pregnane-triol, accompanied by a slight increase of plasma 11-OHCS during the period of administration as compared with the pre-treatment values, when the estimation was carried out in more precisely adjusted conditions as regards individual difference and diurnal change.3. During the period of administration, the effects of ACTH, Su-4885 and dexamethasone tests were studied. It was observed that the excretory patterns of urinary 17-OHCS, 17-KS, Pregnane-diol, Pregnane-triol and plasma 11-OHCS revealed no abnormal depression as compared with the pre-treatment pattern.4. These results reasonably indicate that the basic function of the pituitary-adreno-cortical system was not basically disturbed during the oral administration of the contraceptive agent.5. Similar patterns of urinary and plasma steroids under ACTH, Su-4885 and dexamethasone tests were observed in women who were treated with pseudopregnancy type of Gestagens administration. These results clearly point out the evidences that even massive administration of Gestagens has no particular effect on the basic function of pituitary-adrenocortical system.6. It was assumed that the changes in steroid metabolism of the liver seemed to have occurred during the treatment compared with a pre-treatment period in view of lowered metabolic rate of urinary 17-KS of testosterone in addition to elevated value of serum transaminase and delayed secretory phase of BSP.7. An attempt was made to explain a mechanism of decreased urinary steroid upon the findings of changed steroid metabolism in the liver and by the increasing trend of plasma 11-OHCS which possibly heighten the plasma protein bound cortisol.8. It was interpreted that variations of steroid values in blood and urine upon the administration of combined norethindrone-mestranol was not due to an action of estrogen but by a combination of the two, namely, norethindrone and mestranol.9. From the findings of the tolerance tests, it is proposed that the urinary Pregnanediol, Pregnane-triol, 17-OHCS, 17-KS could equally be applied for the functional test of the pituitary-adrenocortical system of normal women (uncastrated) with a prerequiste of making a fixed environmental condition for estimation.