STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE

Abstract

Circadian variations of the plasma levels of dehydroepiandrosterone, 17-hydroxypregnenolone, pregnenolone and testosterone were investigated by radioimmunoassay in 10 normally menstruating women during the periovulatory period. In 7 of the subjects it was also possible to estimate androstenedione and dihydrotestosterone levels. Blood was withdrawn continuously over a period of 48 h at a rate of 4 ml/h by a non-thrombogenic pump. The circadian rhythm was studied during thirteen 3-h sampling periods (39 h) which were identical in all subjects. Dehydroepiandrosterone, 17-hydroxypregnenolone and pregnenolone showed a marked circadian rhythm with highest mean levels in the morning between 06.00-09.00 h and lowest mean levels during the night between 21.00-24.00 h. The peak levels of individual subjects coincided completely with the highest mean levels in the case of dehydroepiandrosterone, in 9 out of 10 cases with regard to 17-hydroxypregnenolone and in 8 of 10 cases as far as pregnenolone level were concerned. The lowest individual levels were more dispersed around the means than were the individual peaks. The difference between the highest (morning hours: 06.00-09.00) and lowest (evening hours: 21.00-24.00) geometeric mean values was 404% for 17-hydroxypregnenolone, 163% for dehydroepiandrosterone and 71% for pregnenolone. Mean testosterone levels also exhibited an elevation between 06.00-09.00 h which was significant (P < 0.05). However, individual peak values were scattered from 21.00 h of the 1st day to 18.00 h of the 2nd day. The mean concentrations of androstenedione showed a significant increase between 06.00-18.00 h. The individual peaks were widely dispersed. Hence a uniform circadian rhythm correlated to the levels of the .DELTA.5-steroids mentioned above could not be demonstrated in the case of testosterone and androstenedione. An analysis of variance indicated no significant differences between sampling periods as far as dihydrotestosterone levels were concerned. The extent and regularity of the circadian variation in the plasma levels of the .DELTA.5-steroids studied makes it mandatory to standardize very carefully the exact time of blood withdrawal in any longitudinal study. In view of the sharp changes in the plasma levels during the morning hours, sampling during the afternoon period may provide more constant values.