[Nature of estrogen and pregnandiol excretion during the menstrual cycle in otosclerotic patients].
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Eighty consecutive cases of sterility was screened for suspected insufficiency of luteal function. The parameters used in the assessment were one value each for pregnandiol and oestrogen excretion, the basal temperature, the histological picture of secretory endometrium, as well as the activity of endometrial malate dehydrogenase and carbonanhydrase, or malate dehydrogenase and succinic dehydrogenase. Histological irregularities, a short luteal phase as indicated by the basal temperature, early abortion and a pregnandiol excretion of less than 1.9 mg were usually accompanied by low endometrial enzymatic acitvity. A comparison of pregnandiol excretion levels with the other four investigated parameters indicated that the number of negative findings increased with decreasing pregnandiol values. In this way, low oestrogen excretion values occurred more frequently with low pregnandiol values. However, when taken in conjunction with other findings, a low oestrogen value does not seem to be characteristic of luteal insufficiency. In certain cases the suspicion of luteal insufficiency increases with decreasing pregnandiol values and with the number of negative findings concerning basal temperature, endometrial histology and enzymatic activity, as well as oestrogen excretion. According to this point of view the incidence of a presumptive luteal phase defect was 33% in the present investigation.
A study was made of pregnandiol excretion with the 24-hour urine of albino rats, guinea pigs and hamsters at various phases of the esteral cycle. Excretion of metabolities of the principal hestagens (progesterone and 20-alpha progesterone) in the form of alpha- and beta-isomers of pregnandiol proved to be definitely cyclic in character. The periodicity of pregnandiol excretion in the three types of experimental rodents reflected the course of the synthesis and secretion of hestagens, with a delay for a cycle phase. The maximal excretion of both pregnandiol isomeres with the 24-hour urine was abserved in albino rats during the estrus and metestrus, and in guinea pigs and Cricetus auratus W.--during the estrus and diestrus.
Altogether 121 patients with sclerocystic ovaries and 40 normal women aged 16 to 35 years were examined for excretion of estrogens, androgens and pregnandiol with urine and for the blood content of total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDLC) followed by hyperlipoproteinemia (HLP) phenotyping. In the group of normal women, low production of estrogens and pregnandiol was coupled with a reduction in the content of HDLC and an increase in that of TG. In the patients, no relationship was established between the changes in the concentration of estrogens and pregnandiol and the lipid content. Meanwhile the androgen content, which was higher as compared with that in the normal women, correlated with the rise of the TG and TC level, accompanied by a noticeable subsidence of the HDLC level. As compared with the normal persons, the atherogenic types of HLP in the patients occurred 2.2 times as frequently. The data obtained indicate an important role of the primary imbalance of sex steroids in the development of dyslipoproteinemia in young women.
In the present study, we have evaluated the quality control parameters of a new method for the determination of the urinary Pregnandiol and Estriol using a small column AG 1X2 proposed by Bio-Rad Laboratories. The principle of this method is based on a single extraction of steroids by ion exchange and methanol elution under different pH conditions. Compared to the "classical" methods using solvent extraction, the present method has some advantages mainly the elimination of the use of large volumes of solvents and the reduction of the sample volume to be analyzed. The preliminary results showed a recovery of 89,0% - 98,9% (C.V. = 5%) for Estriol and 83,8% - 93, 2% C.V = 5%) for Pregnandiol . The precision of the method evaluated by its repeatability and between-assay reproductibility showed 4% and 6% variation for Estriol and Pregnandiol . The Comparison of the present method with a classical one using Ether/Ethanol (4/1) for extraction gave us a very good correlation.
In 129 patients with sterility or endocrine menstrual cycle disturbances the pregnandiol concentrations in the urine were measured and in the same cycle the endometrium of the 1st day of menstruation histologically examined. The length of the corpus luteum phases was classified into 6 groups (over 14, 11--14, 9--10, 7--8, 1--6, 0 days), also the endometrial findings (over stimulated, normal, slightly, moderately, significantly retarded secretory transformation, no secretory signs). In 77.5% of the cases a complete accordance between the pregnandiol output and the endometrial biopsy was found, in 18% a difference of one step between the two parameters. Only in 4.5% great discrepancies were found, which partly could be explained by simultaneous medication in the same cycle. The two methods do not compete with each other but complete each other, because pregnandiol output is a parameter for corpus luteum function and endometrial histology reveals the reaction of the target organ to the hormonal stimulus. A statement about the etiology of the corpus luteum insufficiency is not possible by these two methods. For that further examination, i.a. serial evaluation of the sexual steroids and gonadotropins in serum are necessary.
Progesterone and some derivatives were tested in a radioimmunoassay (RIA) of digoxin and in a bioassay measuring the 86Rb-uptake into red blood cells as an index of Na+, K+-ATPase activity. The digitalis-like activity of the hormones was compared with that found in chromatographic fractions of material extracted from the urines of pregnant women at term. Progesterone at concentrations greater than 10(-6) M cross-reacted in the RIA, and at 10(-3) M it decreased 86Rb-uptake by 18%. The anaesthetic progesterone derivates 5 alpha-pregnane-3 alpha-ol-20-one and 5 alpha-pregnane-3,20-dione crossreacted to a lesser degree in the RIA and lacked effect in the bioassay. Similar results were obtained with pregnandiol-glucuronide, the major urinary metabolite of progesterone. In contrast, several fractions of the urinary material had significant effects in both assays. It is concluded that the digitalis-like activity of progesterone is not coupled to properties associated with its anaesthetic effects. Furthermore, although progesterone may account for a part of the endogenous digoxin-like substances in serum of neonates and pregnant women, neither progesterone proper nor pregnandiol-glucuronide explains the great amount of digoxin-like substances found in the urines.
An attempt was made to make an early diagnosis of intrauterine growth retardation due to chronic placental insufficiency using ultrasound cephalometry and biochemical tests of placental function. We examined 83 hospitalised patients in whom there was a risk or suspicion of chronic placental insufficiency. For each patient an average of 4 determinations were made of head diameter, 10 of estriol and 3 of pregnandiol urinary excretion, 6 serum HPL and 7 of heat stable alkaline phosphatase (HSAP). Fetal growth retardation was assumed if the last 2 determined head diameters were below the normal curve with the same tendency and with term being well predicted. Biochemical parameters were considered to indicate pathological changes if they were 95% below normal values, with 2 below this range or 3 continuously falling below the normal level. Infants were assessed after birth both neurologically and somatically according to DUBOWITZ. Small for date infants were those whose birth weight was below the 10th percentile (LUBCHENKO). This was found to be the case in 15 out of 83 newborns five of whom were younger than 37 weeks. These 15 could be diagnosed before birth with various degrees of certainty. For estriol and HPL this was 67% or 53% and these two parameters were found to be the most valuable. Cephalometry was found to be less valuable with 20%, pregnandiol levels with 9% and placental HSAP with 33%. Hence it is recommended to perform serial determinations of estriol and HPL in the third trimester of pregnancy in all patients with histories indicative of fetal growth retardation and in those in whom the uterus appears small for date.
BACKGROUND AND AIM: Although numerous investigations have evaluated the association between urinary hormone levels and chronic diseases such as breast cancer and coronary heart disease, there are few data about the reliability of urinary measurements, particularly among premenopausal women. METHODS AND RESULTS: Over a six-month period, levels of estrone-3-glucuronide and pregnandiol-3-glucuronide were measured in both morning spot and overnight urine samples from seven healthy premenopausal women (ages 33-46). During this period, each subject provided one morning spot urine sample and one overnight urine sample per menstrual cycle on the same day of her menstrual cycle. All these samples were taken out of the freezer simultaneously and sent in the same parcel on dry ice to the laboratory for hormone determinations. All samples from each person were assayed simultaneously in the same run and by the same laboratory technician in a blind fashion. The intraclass correlation coefficients (ICC) for estrone-3-glucuronide and pregnandiol-3-glucuronide for the morning spot and overnight urine samples were 0.78 and 0.46 and 0.75 and 0.64 respectively. CONCLUSIONS: These data suggest that morning spot urine determinations are reliable and constitute an efficient alternative to the more complex overnight urine collection for epidemiological evaluation of urinary hormonal profiles.