Some Clinical Observations Upon the Metabolism and Utilization of Crystalline Progesterone

Hamblen, E. C.; Cuyler, W. Kenneth; Powell, Norborne B.; Ashley, Catherine; Baptist, Margaret

doi:10.1210/endo-25-1-13

Cited by 6 publications

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“…2 Ciba Fellow in Clinical Endocrinology. 3 Proluton, supplied by the Schering Corporation, Bloomfield, N. J.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

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

1940

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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'

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“…2 Ciba Fellow in Clinical Endocrinology. 3 Proluton, supplied by the Schering Corporation, Bloomfield, N. J.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

1940

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“…AlsoHamblen and coworkers (3,4) reported that in their studies on progesterone utilization in patients with func' tional irregularities of uterine bleeding no evidence was encountered that crystalline progesterone was metabolized into sodium pregnandiol glucuronidate. These experiments have been elaborated and are now being reported in detail.…”

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A Study of the Metabolism of Crystalline Progesterone

Venning

Browne

1940

Endocrinology

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MONTREAL, CANADÃ\r N 1938 (1) a preliminary report was made on a study of the metabolism of in' II jected crystalline progesterone, which definitely established sodium pregnandiol -1L glucuronidate as an end product in the metabolism of this compound in the hu' man organism. These experiments have been elaborated and are now being reported in detail.Since this work was published Stover and Pratt (2) reported failure to demon' strate any sodium pregnandiol glucuronidate in the urine of women following injec' tions of 15 and 17.5 Rb. u. of progestin (Parke, Davis). AlsoHamblen and coworkers (3,4) reported that in their studies on progesterone utilization in patients with func' tional irregularities of uterine bleeding no evidence was encountered that crystalline progesterone was metabolized into sodium pregnandiol glucuronidate. From endome' trial studies they also conclude that progesterone is inefficiently utilized in these cases. Recently in an advance abstract (19) they state they were only able to recover a total of 3 mg. and 5 mg. of sodium pregnandiol glucuronidate from the urine of 2 patients who had received 90 mg. and 200 mg. of progesterone respectively. In a recent paper Seegar (20) reported that endometrial hyperplasia may respond to pro' gesterone and show changes resembling the physiologic response. The amount of progesterone excreted in the urine as pregnandiol when 50 mg. in 5 mg. doses is given daily, is insufficient to be recovered consistently in measurable quantities in these cases. On the other hand Buxton and Westphal (5) recovered sodium preg' nandiol glucuronidate in the urine of males following large doses of crystalline proges' terone.In the present study the excretion of sodium pregnandiol glucuronidate was fol' lowed under various conditions, and in many cases an attempt was made to correlate this excretion with simultaneous changes occurring in the endometrium. Injections of progesterone were given in the follicular and luteal phase of the menstrual cycle, during pregnancy, after hysterectomy, in cases of secondary amenorrhea with hypoplastic endometria with or without pretreatment with estrogens and in cases of metropathia hemorrhagica with hyperplasia of the endometrium. The effect of estrogens and of gonadotropic hormone upon the excretion of sodium pregnandiol glucuronidate was also investigated.The determination of sodium pregnandiol glucuronidate was made according to the method of Venning (6, 7). There are several points which should be emphasized regarding the estimation of this compound. Firstly, it is impossible to detect less than 2 mg. in a sample of urine, therefore 2 or more days must be pooled and extracted together in order not to overlook small amounts. Secondly, unless care is taken in 707 The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 05 October 2015. at 00:22 For personal use only. No other uses without permission. . All rights reserved.

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The metabolism and utilization of progesterone given intramuscularly to women

Hamblen

Powell

Cuyler

1939

American Journal of Obstetrics and Gynecology

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Some Clinical Observations Upon the Metabolism and Utilization of Crystalline Progesterone

Cited by 6 publications

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

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

A Study of the Metabolism of Crystalline Progesterone

The metabolism and utilization of progesterone given intramuscularly to women

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Some Clinical Observations Upon the Metabolism and Utilization of Crystalline Progesterone

Cited by 6 publications

References 0 publications

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

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

A Study of the Metabolism of Crystalline Progesterone

The metabolism and utilization of progesterone given intramuscularly to women

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Product

Resources

About

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

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