Relation of Urinary Excretion of Estrone to Menstrual Cycle of Normal Woman

Abstract

Although earlier work 1 , 2 had failed to demonstrate a greater efficacy of the intravaginal method of assaying estrone, Berger 3 reported that l/12th of the parenteral unit of estrone could be detected by intravaginal administration. Lyons and Templeton 4 reported that by their intravaginal method 1 /200th of a rat unit of estrone could be detected. The latter workers reported estimates of the amount of urinary estrogenic substance excreted daily, at 4 periods in the normal menstrual cycles of 4 nulliparous women.

It seemed desirable to follow the daily excretion of estrogenic substance throughout the cycle, and for this purpose the cooperation of 2 normal nulliparous women was secured. For more than a full cycle these women collected 24-hour samples of urine preserving them with hexylresorcinol (1 part to 20 of urine) and storing them at 0°C. Crude extracts were made of a fraction of each sample according to the method formerly given, 4 and these extracts were administered vaginally to rats by means of a Breed and Brew 0.01 cc. micro-pipette to which was attached a short rubber tube such as is used on a blood-diluting pipette. Care was taken to remove any of the extract adhering to the outside of the pipette before inserting in the vagina.

Of a group of 40 ovariectomized adult rats, 24 were found sufficiently uniform and consistent in their reaction to l/200th of a rat unit of Progynon B∗ administered intravaginally, to permit their use as assay animals. In standardizing the rats as well as in testing, the preparations were administered in 2 0.01 cc. daily doses and the reaction read 24 hours after the second administration.

The minimal effective dose was considered the smallest amount of extract that would produce a vaginal smear showing that definite epithelial growth and cornification had been stimulated in at least 2 standardized rats—lower doses giving negative reactions and higher doses producing more complete cornification.

Case A was studied throughout a 30-day cycle (an average length for this woman). Case B was studied throughout a 21-day cycle, the average length of cycle for this woman being 25 days. Given in the accompanying chart and Table I are the number of intra-vaginal units excreted daily by Case A, the 24-hour urinary volumes and the minimal effective urinary equivalent. It will be observed that the excretion of estrogenic substance reached two definite peaks during the menstrual cycle. One of these at mid-cycle (ovulation time), and the other, just before menstruation. In the case of the 21-day cycle, the mid-cycle peak occurred on day 9 and the premenstrual peak on day 17. Several other workers 5 , 6 , 7 have resubcutaneous method will be minimized by the intravaginal method, since rates of absorption and excretion are important variables to be considered in accounting for these differences. No attempt is made to identify the urinary estrogenic substance assayed in this research with any of the various estrones. Those interested in translating the unitages reported herein to one of the other systems should be able to do so through the medium of the Progynon B standardization (see also Schoeller, W., et ah, Klin. Wchnschr., 1935, 14, 826.).