The metabolism and utilization of progesterone given intramuscularly to women

Hamblen, E. C.; Powell, Norborne B.; Cuyler, W. Kenneth

doi:10.1016/s0002-9378(39)90349-2

Cited by 10 publications

(2 citation statements)

References 33 publications

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“…The presence of pregnandiol in association with amenorrhea is suggestive of pregnancy and is to some extent used as a diagnostic aid. 7 The absence or diminution of pregnandiol during pregnancy is indicative of a patho¬ logic condition such as threatened abortion or death of the fetus.8 There is some difference of opinion as to the metabolism of pregnandiol in toxemias of pregnancy and the role of the kidney in its excretion.9 The metab¬ olism of progesterone in the body has been adequately described by Hamblen,10 Venning,11 and Cope6 and includes ovarian, hepatic, uterine and renal factors. Our interest was stimulated by 2 cases of pseudohermaphroditism which we had occasion to study and in which pregnandiol titers were determined.…”

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confidence: 99%

Pregnandiol Excretion in Female Pseudohermaphroditism

Genitis¹,

Bronstein²

1942

JAMA

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The end product of progesterone metabolism, pregnandiol, is determined as sodium pregnandiol glucuronidate by a gravimetric method developed by Venning and Browne.1Estimations of this complex have been made by various investigators in normal and pathologic menstrual periods, in normal pregnancy, abortions, toxemias and, lastly, in cases of the adrenogenital syndrome.2 Except in an isolated case (a child aged 3 years), there have been no data available among children.3The accumulated literature to date has already been well summarized, but it may be well to recall a few pertinent facts regarding the excretion of pregnandiol. This compound is excreted in the urine during the luteal phase of the normal menstrual cycle when the corpus luteum is active and absent during the first half of the intermenstrual phase. The amount of pregnandiol determined for the whole cycle may vary from 34 to 54 mg., although the daily output may be 2 to 10 mg.4During pregnancy the compound is excreted in increasing quantities in the urine as gestation proceeds, when its production is attributed to the placenta. The mean figure as given by Venning 5 is 75 mg. a day and by Cope 6 as 55 mg. daily, with wide variations. The presence of pregnandiol in association with amenorrhea is suggestive of pregnancy and is to some extent used as a diagnostic aid.7 The absence or diminution of pregnandiol during pregnancy is indicative of a patho¬ logic condition such as threatened abortion or death of the fetus.8 There is some difference of opinion as to the metabolism of pregnandiol in toxemias of pregnancy and the role of the kidney in its excretion.9 The metab¬ olism of progesterone in the body has been adequately described by Hamblen,10 Venning,11 and Cope6 and includes ovarian, hepatic, uterine and renal factors. Our interest was stimulated by 2 cases of pseudohermaphroditism which we had occasion to study and in which pregnandiol titers were determined. We specu¬ lated as to the diagnostic value of pregnandiol in these cases, and, because of the paucity of data in the young age group, determinations on other children were made for comparison. These include a pubescent boy and girl, 2 girls with prolonged menstrual bleeding, a pre¬ cocious pubescent child and a Lorain-Levi dwarf.12These are not included in this report.The need for total and complete urine specimens was stressed by several groups, but recently Bachman 8 suggested that only a portion of the urine is necessary for analysis. He felt that the general trend of values gives enough information in cer¬ tain conditions, especially in the last months of preg¬ nancy.We expected the amount of pregnandiol in the urines of children to bvery small ; therefore, in order that a sufficient yield of .he com¬ pound could be obtained large pooled volumes of urine were extracted. In most instances the urines were pooled into forty-eight hour lots and the total vol¬ ume was extracted. Some¬ times with this procedure the final weighed precipitate was of no significance.

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Pregnandiol Excretion in Female Pseudohermaphroditism

Genitis¹,

Bronstein²

1942

JAMA

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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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Die Bedeutung der Pregnandiolausscheidung im Harn f�r die Gyn�kologie und Geburtshilfe.

Plötz

1950

Arch. Gynak.

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The metabolism and utilization of progesterone given intramuscularly to women

Cited by 10 publications

References 33 publications

Pregnandiol Excretion in Female Pseudohermaphroditism

Pregnandiol Excretion in Female Pseudohermaphroditism

A Study of the Metabolism of Crystalline Progesterone

Die Bedeutung der Pregnandiolausscheidung im Harn f�r die Gyn�kologie und Geburtshilfe.

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