URINARY EXCRETION OF PREGNANDIOL COMPLEX BY MALES I. FOLLOWING INTRAMUSCULAR ADMINISTRATION OF PROGESTERONE¹

Abstract

I TUDIES by Venning and Browne (i) and by members of our group (2) have in' dicated that a number of factors is associated with the metabolism of endog' enous progestin and its ultimate excretion as sodium pregnandiol glucuronide; an important one of these apparently is the functional adequacy of the endometrium (2). Furthermore, members of our group (2, 3) and Stover and Pratt (4) have reported that, in the case of the female, exogenous progesterone, when given intramuscularly in oily solution, apparently is not metabolised into the-pregnandiol complex to any sig' nificant degree. It has been suggested that this might be the cause of the poor endo' metriotropic responses commonly observed following this form of therapy in patients with estrogenic bleeding. In view of these gynecologic findings, it seemed advisable to investigate the metabolism of exogenous progesterone by healthy males.While these studies of ours were under way, the observations of Buxton and Westphal (5) were reported. These workers reported the demonstration of the preg' nandiol complex in the urines of 2 males with Addison's disease and of one healthy male, all of whom had been receiving daily injections of 30 mg. of progesterone. In view of this report, our studies were extended and are reported at this time. METHODOur first step was to investigate the renal permeability of the male to ingested Na pregnandiol glucuronide. The previous paper dealt with this phase of the studies.Progesterone in oil 3 in concentration of 10 mg. to 1 cc. of oil, was given intramuscularly to 6 apparently healthy males, whose ages ranged from 23 to 38 years. These subjects had volunteered for these studies. Two general plans of treatment were followed: the use of a single injection of 20 mg.; and the employment of series of injections in daily doses, which ranged from 10 to 30 mg., for 4 days. Following the use of a single injection, all urine was collected in 24'hour samples for 72 hours after the injection was given. Following the use of daily injections for 4 days, collection of urine was started at the time of the first injection and continued, as 24'hour samples, for 5 to 13 days. Each 24'hour specimen of urine collected was quantitated by the improved method of Venning (6), for its total content of Na pregnandiol glucuronide. The method of calculation and correction, advised by Venning, was employed by us. Melting points were determined on single precipitates when possible; on some oc'