Urinary Excretion Of Pregnanediol Research Articles

Serotonin, 5-hiaa, total estrogen and pregnanediol excretion in urine during therapeutic saline abortion.

In 24 patients, who underwent therapeutic abortion for various reasons between the 17th and 26th week of pregnancy, urinary excretion of serotonin, 5-HIAA, total estrogens, and pregnanediol were measured before, during and after the intra-amniotic injection of hypertonic saline. 20% hypertonic saline solution (160-500 ml) was given by transabdominal injection over a period of 5 min. The four hormones or metabolites were measured during six periods: I; 12-24 hrs, and II: 0-12 hrs before saline administration, III: 0-12 hrs after saline administration, IV: 0-12 hrs during aborion, V: 0-12 hrs and VI: 12-24 hrs after abortion. The results point to the active participation of serotonin in the process of fetal expulsion, as serotonin was increased by over 100% (from 20-22 to 43-47 mu-g/12 hrs) during periods III-IV, and its metabolite 5-HIAA, too, increased by nearly 60% (from 2.4-2.5 to 3.3-3.9 mg/12 hrs). They decreased during the post-abortive periods V-VI. On the other hand, total estrogens decreased only slowly, but continuously, during all 6 periods (4.9, 4.3, 3.4, 3.1, 1.8 and 1.4 mg/12 hrs). Pregnanediol, beginning with 12 mg/12 hrs showed a slight increase during periods III-IV (14.5 and 15.6 mg/12 hrs) and a decrease during periods V-VI (8.0 and 5.8 mg/12 hrs). These findings are interpreted as indicating the disruption of feto-placental function affecting estrogens during periods III-VI. They might demonstrate an accelerated hydrogenation of progesterone into pregnanediol during periods III-IV, followed by a sharp decreased in progesterone/pregnanediol production during periods V-VI.

Comparison of prostaglandin F2α and hypertonic saline for induction of midtrimester abortion

Midtrimester abortions were induced in two compatible groups of patients in the second trimester by intra-amniotic instillation of either prostaglandin F2α or a 20 per cent sodium chloride solution. Nine of the 10 patients in the prostaglandin group aborted completely, with a mean abortion time of 15.16 hours. All of the 10 patients in the saline group aborted completely, and the mean abortion time was 20.34 hours. One patient in the prostaglandin group failed to abort during the prostaglandin instillation, and abortion finally had to be completed surgically. The 2 groups were compared with regard to uterine activity and plasma levels of progesterone, human prolactin, human placental lactogen, and cortisol, as well as urinary excretion of estrone, estradiol, estriol, and pregnanediol. The endocrine changes were rather similar in the 2 groups. The side effects in the 2 groups were carefully studied and found to be fairly similar although gastrointestinal symptoms were more frequent in the prostaglandin group. Lactation in the postabortion period was more frequent in the prostaglandin group. The similarities suggest that the mechanism of abortion may not be much different with the 2 methods. To decide which one of the methods is safest requires the study of much larger groups of patients for comparison.

Changes in renal water and electrolyte excretion occurring before and after induced ovulation and their relation to total oestrogen and pregnanediol excretion.

SummaryOvulation was induced by gonadotrophin therapy in eight women with secondary amenorrhoea. During ovarian inactivity and throughout the preovulatory and luteal phases of the induced cycles continuous measurements were made of mean urine flow and the urinary excretion of total solute, sodium, potassium, urea, total oestrogens and pregnanediol. The preovulatory rise in total oestrogen excretion was associated with a reduction in sodium output whereas the excretion of greatly increased amounts of pregnanediol after ovulation was associated with an increase in sodium excretion. Maximal pregnanediol excretion tended to coincide with a second peak in total oestrogen excretion but was unaccompanied by any further rise in sodium output. Night sodium excretion was disproportionately increased after ovulation and was associated with an increment in night potassium excretion. Alterations observed in total solute excretion and urine flow were mainly determined by changes in sodium excretion.

Serum progesterone in nonpregnant women: I. Comparative study of serum progesterone concentration and urinary pregnanediol excretion

Serum progesterone concentration and urinary pregnanediol excretion were measured simultaneously in 54 patients. The values have a logarithmic distribution. Mean values and normal range were: for serum progesterone in proliferative phase, 0.44 ng. per milliliter (0.15 to 1.30); in secretory phase, 5.6 ng. per milliliter (1.79 to 17.65); for urinary pregnanediol in proliferative phase, 0.42 mg. per 24 hr. (0.15 to 1.20), in secretory phase, 3.48 mg. per 24 hr. (1.22 to 10.13). The correlation coefficient between serum progesterone and urinary pregnanediol is 0.82, and there is almost no discrepancy between the levels of these two hormones. It is suggested that a single hormonal determination after day 20 of the cycle could be sufficient for the detection of a functioning corpus luteum, and preference is given to the progesterone measurement. In anovulation and secondary amenorrhea, lack of cyclic variation occurred and progesterone remained within proliferative phase range. In prolonged cycles, a premenstrual rise of progesterone was observed in some cases, suggesting late ovulation. In hirsutism without polycystic ovaries, hormonal evidence of ovulation was sometimes present. A luteal phase defect was suggested by persistent progesterone concentrations in the lower range of the luteal phase, often associated with abnormal basal body temperature and an atypical endometrial biopsy. Clomiphene citrate induced ovulation in some patients but in half of them a lower extent and shorter duration of progesterone rise were observed as compared to normal cycles, suggesting a probable luteal deficiency.

Serum progesterone in nonpregnant women: II. Correlation between serum progesterone and some other luteinization parameters

Correlation between serum progesterone concentration, urinary pregnanediol excretion, endometrial biopsies, vaginal cytology, and basal body temperature was performed to determine the most dependable method for assessing the presence of a functioning corpus luteum. Vaginal cytology was not completely reliable as it had relatively poor correlations. A biphasic basal body temperature was always associated with a rise of progesterone to luteinization range, but a monophasic chart did not necessarily indicate anovulation. This fallacy, together with difficulties in recording and interpretation, made basal body temperature not totally accurate for assessing luteal activity. Premenstrual endometrial biopsies gave the best correlation with hormonal assays. It is thus concluded that serum progesterone determination and properly interpreted endometrial histology are the most accurate diagnostic luteinization parameters.

EFFECTS OF SYNTHETIC LH/FSH-RELEASING HORMONE (LRH) ON PLASMA LH AND FSH IN AMENORRHOEIC WOMEN

ABSTRACT Eight amenorrhoeic women were given 100 μg synthetic LRH (Hoechst) iv and im, respectively, at an interval of 2 weeks. Four of the women received the iv injection first and four the im injection. The urinary excretion of oestrogens and pregnanediol was low and unaltered throughout the test weeks. The effects of LRH were compared by serial measurements of the plasma LH and FSH during 8 h. The initial response of LH for up to 25 min and that of FSH for up to 60 min were equal whether LRH was given iv or im. The difference appeared later. Four hours after the injection the mean increase of LH to iv injection was 0.5 ng/ml (N. S.), while that to im injection was 1.9 ng/ml (P < 0.01). The corresponding values for FSH were 1.3 (P < 0.05) and 3.2 (P < 0.001). The effect of LRH administration im was thus found to be larger and more prolonged.

Regulation of the human menstrual cycle.

Methodological and investigative advances in the field of reproducti ve endocrinology have produced new information regarding the regulation of the menstrual cycle. The synthesis and release of gonadotropins by the pituitary gland is regulated by an single neurohormone or by 2 humoral factors. The mechanism of and experiments with this factor are described. Steroids can modify the process. The pituitary system reacts with the ovarian system. Cycles are charted for LH and FSH conce ntrations in the blood serum during normal menstrual cycles. These are charted against basal temperature cycles and progesterone concentration urinary estrogen and pregnanediol excretion through the cycle. Further research should examine temporal and physiological relationships between ovarian steroids and the gonadotropins which regulate their formation.

A STUDY OF A PREGNANCY WITH LOW ESTROGEN PRODUCTION DUE TO PLACENTAL SULFATASE DEFICIENCY

A pregnancy has been investigated in which maternal urinary excretion of estrogens was abnormally low. The excretion of estrone, estradiol and estriol was, respectively, 15%, 15% and 5% of levels found in normal pregnancy. Urinary pregnanediol excretion was within the normal range. There was no evidence of either fetal abnormality or growth retardation. A normal male baby was delivered by cesarian section at 39 weeks gestation. Both in vivo and in vitro the placenta was shown to have a normal potential for metabolism of 3β-hydroxy-androst-5-en- 17-one (DHEA) to estrogens, but lacked ability to hydrolyze androst-5-en-17-one-3β-yl sulfate (DHEAS). In vitro incubation experiments with the substrates pregnenolone-7-3H sulfate, estrone- 4-14C sulfate and nitrocatechol sulfate indicated that the placenta was also deficient in sulfatase activity with respect to these substrates. Cord plasma levels of l6α-hydroxyandrost-5-en-17-one- 3β-yl sulfate (160HDHEAS) and pregn-5-en-2O-one-3β-yl sulfate (PS) were in the ra...

STUDIES ON SUSTAINED CONTRACEPTIVE EFFECTS WITH SUBCUTANEOUS POLYDIMETHYLSILOXANE IMPLANTS

ABSTRACT Ovarian function was assessed in 10 healthy young women, before and after the insertion of 3 or 4 polydimethylsiloxane capsules filled with 20 mg of megestrol acetate. Each capsule released in vitro, approximately 20 μg/24 h of the hormone. Daily determination of the urinary excretion of FSH, LH, fractionated oestrogens and pregnanediol were performed in all subjects during one control cycle, the first and the third cycle after the insertion of the capsules. Out of 10, 8 control cycles were ovulatory according to all the parameters investigated. This compares with 15 ovulatory cycles out of a total of 20, examined after the insertion of the capsules. During treatment no changes were observed in the FSH excretion pattern; the mid-cycle LH peak was present in all ovulatory cycles, although it was usually much less evident under the action of megestrol acetate. The excretion of oestradiol was significantly increased in all subjects (P < 0.05) during the first cycle following implantation. Oestrone and oestriol excretion was also generally higher in patients bearing PDS capsules; however, this difference was not statistically significant. Pregnanediol levels were not affected by the treatment in all cycles considered to be ovulatory on the basis of all the parameters. The menstrual bleeding pattern did not change in the majority of cases. One patient had, during treatment with 3 capsules, two profuse break-through bleedings whereas another one became amenorrhoic two months after the insertion of 4 implants. It is concluded that megestrol acetate sustained release preparations do not inhibit ovulation under the experimental conditions used.

Detailed hormonal studies during and after pregnancy in a previously hypophysectomized patient.

ABSTRACT This is a report on detailed hormonal studies before, during, and after pregnancy in a hypophysectomized patient who conceived after treatment with human gonadotrophins. On the basis of the results the following conclusions were drawn: In a patient who, judging by numerous investigations, no longer had any production of pituitary gonadotrophic hormones, it was possible by treatment with human gonadotrophic hormones to induce ovulation, without further stimulation to attain conception and preserve the conceptus, to carry through a normal pregnancy, ending at term in vaginal delivery of a normal infant. In this patient, whose pituitary corticotrophin production had totally ceased or had been negligible before the pregnancy, the endocrine state appeared to be completely normalized during pregnancy; thus: on unchanged corticosteroid medication the mean plasma corticoid concentration as well as the urinary excretion of corticoid metabolites, 17-ketogenic steroids, and 17-ketosteroids were considerably higher during than after the pregnancy, the urinary excretion of pregnanediol, oestriol and chorionic gonadotrophin was normal during the pregnancy. Moreover, the results of metyrapone tests before, during and after the pregnancy, ACTH stimulation test after delivery, and measurements of diurnal fluctuations in the concentration of plasma cortisol during the pregnancy are reported. The increased steroid production during pregnancy may be partially explained as a consequence of the activity in the foeto-placental unit which, however, can hardly have been quantitatively decisive. It must be presumed, therefore, that as a result of the pregnancy ACTH or an ACTH-like factor has been secreted, stimulating the maternal adrenal. It is assumed that the corticotrophin has been produced in the placenta and that it has passed to the maternal circulation.

A study of pregnancy with low estrogen production due to placental sulfatase deficiency.

A pregnancy has been investigated in which maternal urinary excretion of estrogens was abnormally low. The excretion of estrone, estradiol and estriol was, respectively, 15%, 15% and 5% of levels found in normal pregnancy. Urinary pregnanediol excretion was within the normal range. There was no evidence of either fetal abnormality or growth retardation. A normal male baby was delivered by cesarian section at 39 weeks gestation. Both in vivo and in vitro the placenta was shown to have a normal potential for metabolism of 3β-hydroxy-androst-5-en- 17-one (DHEA) to estrogens, but lacked ability to hydrolyze androst-5-en-17-one-3β-yl sulfate (DHEAS). In vitro incubation experiments with the substrates pregnenolone-7-3H sulfate, estrone- 4-14C sulfate and nitrocatechol sulfate indicated that the placenta was also deficient in sulfatase activity with respect to these substrates. Cord plasma levels of l6α-hydroxyandrost-5-en-17-one- 3β-yl sulfate (160HDHEAS) and pregn-5-en-2O-one-3β-yl sulfate (PS) were in the ra...

Suppression of the midcycle LH surge by a low-dose mestranol-lynestrenol oral combination

In a group of nine ovulating women receiving a low-dose mestranol-lynestrenol combination, the daily fluctuations of plasma LH concentration were measured by radioimmunoassay. In each woman a pre-treatment control cycle was investigated basing the occurrence of ovulation on the biphasic nature of the basal body temperature, the typical midcycle LH surge and the urinary pregnanediol excretion. The daily administration of 0.040 mg mestranol — 1.0 mg lynestrenol produced in all volunteers a complete suppression of the midcycle LH surge. In half of the cases the basal LH pattern showed unstable and slightly elevated levels. Administration of 0.040 mg mestranol alone produced a strong stimulating effect on LH secretion. On the other hand, administration of 1.0 mg lynestrenol alone produced the suppression of the LH discharge without changing the basal values.

Treatment of menometrorrhagia with an anti-oestrogen.

SUMMARYSix women with menometrorrhagia, two with anovular cycles and four with ovular cycles, have been studied, before, during and after treatment with tamoxifen, a competitive inhibitor of the binding of oestrogen to the endometrium. During treatment the urinary pregnanediol excretion of the women with anovular cycles rose and a modified secretory transformation of the endometrium occurred. Ovulation occurred during treatment in all the patients suffering from ovulatory menorrhagia. Most patients noted a diminution in the amount and duration of bleeding and there was a tendency for the previously irregular bleeding to occur at regular intervals during treatment.

CONTRACEPTION BY AN INJECTABLE LONG-ACTING OESTROGEN-PROGESTOGEN AGENT. III

ABSTRACT Twenty-two fertile women were treated cyclically in from 4–30 cycles (mean 15.5) with a total of 341 injections of Deladroxate®, an injectable, long-acting oestrogen-progestogen. The injections were administered on the 8th (7th–9th) day of each cycle. Before treatment, the last pre-treatment cycle was controlled by means of daily recordings of the basal body temperature (BBT), urinary excretion of pregnanediol and total pituitary gonadotrophins at certain intervals, and by endometrial biopsies obtained late in the cycle. The effects of Deladroxate® on ovulation, on pituitary gonadotrophic function, and on the endometrium were controlled by the above mentioned parameters during cycles 1, 3, and 6, and all assessments were repeated after discontinuation of treatment. During treatment, there was a statistically significant fall in gonadotrophin excretion values (as compared with the pre-treatment values), and the fall was found to be gradually progressive during treatment. After discontinuation of treatment, there seemed to be a tendency towards an increase in the excretion values. Suppression of ovulation as determined by means of the pregnanediol excretion during treatment, was effective in nearly all of the treatment cycles checked. The fall in pregnanediol excretion was also gradually progressive during treatment, while there was a slight increase in excretion values in the post-treatment period. During treatment, 79 BBT curves were recorded. Nearly 50 % were monophasic, indicating anovulatory cycles, 17 curves were biphasic, but with the rise in temperature occurring at non-characteristic times in the cycles, 18 curves were classified as thermogenic because of a rise in temperature occurring within 24 hours after the injection, and 5 curves were not assessable. During the first month after discontinuation of treatment, 8 out of 10 recorded curves were monophasic. Out of 53 endometrial biopsies obtained around the 23rd day of the cycle, 31 were of the mixed phase type, but showing a predominance of proliferative patterns, 15 were of the secretory type, and 7 were purely proliferative. Out of 15 biopsies obtained in the post-treatment period, only two were of the mixed phase type, 12 were proliferative and one was purely secretory.

ENDOCRINE STUDIES IN POST‐MENOPAUSAL WOMEN WITH OVARIAN TUMOURS

SummaryAn endocrine assessment was made in 78 post‐menopausal women.The urinary excretion of oestriol was greater than 10 μg. per 24 hours in 14 out of 31 cases with malignant ovarian tumours, in 2 out of 24 cases with benign ovarian tumours, and in 6 out of 23 cases without ovarian tumours. Although the urinary oestriol excretion was increased in all 8 cases with mucinous carcinoma it was raised in only 4 out of 18 cases with serous carcinoma. Some of the greatest amounts of urinary oestriol were found in cases without ovarian tumours.The urinary excretion of pregnanediol was increased in 6 out of 18 cases. These six patients also had increased oestriol excretion.The excretion of steroids was normal after oöphorectomy.Tests of adrenal cortical activity and ovarian vein blood analysis also point to the diseased ovary as the site of increased steroid synthesis.The correlation of increased urinary oestriol with vaginal cornification index was fair, but with vaginal bleeding and endometrial activity was poor.

The effect of dexamethasone on the urinary excretion of steroids during pregnancy.

SummaryThe urinary excretion of oestriol, total 17‐oxosteroids, pregnanediol and Pettenkofer chromogens were studied in eight pregnancies before, during and after the administration of dexamethasone. Both the oestriol and 17‐oxosteroid levels declined during the period of drug administration. The change in Pettenkofer chromogens was less consistent but generally paralleled the 17‐oxosteroid values. Pregnanediol excretion greatly increased in three subjects, decreased in one and was relatively unchanged in the other patients. The present studies support the concept that placental pregnenolone is utilized by the fetal tissues for the biosynthesis of oestrogen precursors and by the placenta for progesterone synthesis.

Sodium space and electrolyte excretion during the menstrual cycle

Exchangeable sodium spaces were measured at intervals during the menstrual cycle in normotensive subjects under controlled sodium intake. Urinary excretion of sodium, potassium, and creatinine was also measured daily, along with daily weights and basal body temperature. The time of ovulation was determined based upon basal temperatures and urinary excretion of pregnanediol. The results were compared to those of hypertensive subjects. No significant change was noted in sodium space during the phases of the menstrual cycle. The aldosterone secretion rates and plasma renin activity in hypertensive patients of an earlier study are also discussed.

The interpretation of urinary oestrogen and pregnanediol excretion in pregnant women receiving corticosteroids.

SummaryThe urinary excretion of oestrogens and pregnanediol of 17 pregnant women who were receiving corticosteroids was measured. In all 10 patients who received less than 75 mg. cortisol (or its equivalent) daily and who gave birth to infants of satisfactory weight and without fetal abnormality, oestrogen excretion was within the normal range. The 4 patients who received less than 75 mg. cortisol daily but who showed subnormal oestrogen excretion gave birth to infants with retarded fetal growth or, in 1 instance, with hypoplastic adrenal glands. All 3 patients who received more than 75 mg. cortisol daily showed subnormal oestrogen excretion. Urinary pregnanediol excretion was within the normal range in 5 out of the 7 pregnancies in which oestrogen excretion was subnormal.It is concluded that subnormal oestrogen excretion in pregnant women who are receiving less than 75 mg. cortisol (or equivalent) daily is indicative of a failure of the fetus to thrive.

Effect of pregnenolone sulfate administration on the excretion of steroid hormones in pregnant women

The urinary excretion of pregnanediol, estriol, total 17-ketosteroids and Pettenkofer chromogens were studied after the intravenous administration of 100 or 200 mg of pregnenolone sulfate to pregnant women. The maximum excretion values were observed for 17-ketosteroids and Pettenkofer chromogens within 24 hours. Estriol excretion also showed a substantial rise within 72 hours. The excretion pattern of pregnanediol mirrored that of estriol but with minimum initial rise.

Progesterone, pregnancy and the augmented plasma insulin response.

ABSTRACT Intramuscular progesterone, 300–400 mg, was given daily to 5 normal men and to 2 hysterectomized women for 6 days to assess the role of this steroid in the development of hyperinsulinemia observed during pregnancy. Twentyfour hr urinary pregnanediol excretion increased to levels that were within the range of late gestation. On days 5 and 6 plasma glucose concentrations during oral glucose and intravenous tolbutamide tolerance tests were unchanged, but plasma insulin responses including fasting levels were significantly increased above control values. Patterns of insulin response were similar to those measured during studies of 10 normal women in late pregnancy. Progesterone effects were independent of any changes in fasting plasma glucose, free fatty acids, serum cortisol or immunoreactive growth hormone. These results suggest that progesterone, like pregnancy, evokes an enhanced plasma insulin response to insulinogenic stimuli as pancreatic islet adjustment to peripheral insulin antagonism evolv...