Use of small urine samples to monitor pregnanediol excretion in normal women: measurement of pregnanediol to oestrogen ratios.
Explore the source record for details and available documents.
Adult↗
SEARCH · Search PubMed
Results for “Pregnanediol”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[Studies of pregnanediol in urine. IV. Behavior of pregnanediol in urine in healthy and eucrinic subjects after DOCA administration].
Explore the source record for details and available documents.
Body Fluids↗
The effect of pregnanediol and pregnanediol glucuronide on bilirubin conjugation by rat liver slices.
Explore the source record for details and available documents.
Animals↗
Indices of ovulation: comparison of plasma and salivary levels of progesterone with urinary pregnanediol.
An increased daily excretion of pregnanediol, relative to that early in the menstrual cycle, is often taken to be evidence that a woman has ovulated. This paper assesses the value of alternative procedures for this purpose. Urine, plasma and saliva samples were collected during a 24-h period from 20 women during the follicular phase and from 20 women during the luteal phase. The 24-h excretion of pregnanediol was compared with (1) the concentration of progesterone in plasma, (2) the concentration of progesterone in saliva, (3) the concentration of pregnanediol in small urine samples, (4) the rate of excretion of pregnanediol and (5) the ratio of pregnanediol to creatinine in small urine samples. Each analyte increased substantially during the luteal phase. The median increases (ratio of luteal to follicular phase values) were 14.8, 3.2, 10.6, 11.9 and 11.1 respectively. By comparison, the median increase in 24-h pregnanediol output was 9.2. When the other analytes were used instead of the 24-h excretion of pregnanediol to assess the possibility of ovulation, the incidence of misclassifications (follicular samples classed as luteal and luteal samples classed as follicular) was 0, 12.8, 5.9, 2.0 and 1.0% respectively. It was concluded that the most satisfactory alternative to the measurement of 24-h pregnanediol output for the biochemical assessment of ovulation based on progesterone production was the measurement of the concentration of progesterone in plasma; the least satisfactory alternative was determination of the concentration of progesterone in saliva. If blood was not available, measurement of the ratio of pregnanediol to creatinine in a small urine sample was the preferred method.
Adult↗
Utility and predictive value of a rapid measurement of urinary pregnanediol glucuronide by enzyme immunoassay in an infertility practice.
STUDY OBJECTIVE: To assess the clinical utility of measuring urinary pregnanediol glucuronide in random samples in an infertility practice. DESIGN: Samples of urine were collected from patients approximately 3 weeks from their last menstrual period to ascertain if ovulation had occurred. Each sample was tested for specific gravity before analyzing for pregnanediol glucuronide. Simultaneous venipuncture was performed to compare results from the urinary assay to quantitative measures of serum progesterone (P). SETTING: All patients were randomly sampled. PATIENTS: Three hundred ninety women undergoing pituitary down regulation with leuprolide acetate were chosen for study because they routinely initiate medication after documentation of ovulation. OUTCOME MEASURES: The performance of the urinary pregnanediol glucuronide was evaluated as to its sensitivity, specificity, predictive value, and test efficiency compared with a serum measurement of 2.5 ng/mL and 10.0 ng/mL. RESULTS: The performance characteristics of the pregnanediol glucuronide assay were directly related to the hydration status of the patient at the time of sample collection. Regardless of urine specific gravity, if pregnanediol glucuronide was qualitatively detected (greater than 3 micrograms/mL), serum P was greater than 2.5 ng/mL. However, in cases in which pregnanediol glucuronide was undetected (less than 3 micrograms/mL), results were only accurate when the specific gravity was greater than or equal to 1.020. When comparing urinary pregnanediol glucuronide values to serum greater than 10 ng/mL, both specificity and predictive value of a positive test decreased because of increased numbers of false-positive results. CONCLUSIONS: The enzyme immunoassay measurement for pregnanediol glucuronide may replace the use of serum P in documenting the ovulatory status of many patients. However, all specimens must be checked for specific gravity and if less than 1.020, a serum P should be used to ensure accuracy.
Female↗
First-trimester rapid semiquantitative assay for urine pregnanediol glucuronide predicts gestational outcome with the same diagnostic accuracy as serial human chorionic gonadotropin measurements.
OBJECTIVE: The purpose of this study was to compare a single urine pregnanediol glucuronide measurement with serial human chorionic gonadotropin titers for the prediction of abnormal early gestations. STUDY DESIGN: We analyzed multiple urine pregnanediol glucuronide levels in 19 spontaneously conceived pregnancies during the first 49 days of gestation. A semiquantitative measurement was made by rapid enzyme immunoassay (Phase Check) at different urinary dilutions. To establish the reliability of semiquantitative urine pregnanediol glucuronide assay to detect abnormal gestation, this test was compared with human chorionic gonadotropin doubling times derived from a previously described normal population. A receiver-operator characteristic curve was constructed for each test, and areas under the curve with corresponding SEs were calculated. The critical-ratio z test was used to compare the two assays. RESULTS: The receiver-operator characteristic curves indicate that both urine pregnanediol glucuronide and human chorionic gonadotropin doubling can predict early gestational complications (p < 0.05). The area under the curve for human chorionic gonadotropin doubling time was 0.809 +/- 0.048, and urine pregnanediol glucuronide had an area of 0.702 +/- 0.072. Comparison of the area under the curve revealed that the ability of urine pregnanediol glucuronide to predict early gestational failure was indistinguishable from that of human chorionic gonadotropin doubling times (p > 0.05). A 1:2 dilution of urine gave the best results in the semiquantitative urine pregnanediol glucuronide test (Phase Check). CONCLUSIONS: On the basis of receiver-operator analysis, semiquantitative urine pregnanediol glucuronide measurements predict abnormal early gestations as well as serial human chorionic gonadotropin measurements do. The ability of a single urine semiquantitative assay (Phase Check) to predict early gestational complications offers a convenient screening tool that may identify women with abortive or ectopic pregnancies before the onset of symptoms.
Abortion, Spontaneous↗
Persistent pregnanediol glucuronide secretion after gonadotrophin suppression indicates adrenal source of progesterone in premature ovarian failure.
A 2-3 fold higher urinary pregnanediol glucuronide excretion has been observed in women with premature ovarian failure, compared with age-appropriate menopausal women. Progesterone, the precursor of urinary pregnanediol glucuronide, is a secretory product of either adrenal or ovarian origin. We postulated that suppression of pituitary gonadotrophin secretion by down-regulation with a long-acting gonadotrophin-releasing hormone agonist, leuprolide acetate, would decrease ovarian but not adrenal pregnanediol glucuronide. This would demonstrate a major difference in the ovarian hormonal milieu of these two groups of women. Four volunteers with premature ovarian failure collected daily first morning voided urine samples for 1 month prior to leuprolide acetate administration. Leuprolide acetate was then administered monthly for 3 months while continuing daily urinary collection. Luteinizing hormone (LH), follicle stimulating hormone (FSH), and pregnanediol glucuronide were measured in all samples and normalized for creatinine. Comparisons of pre- and post-median values for luteinizing hormone (LH), FSH, and pregnanediol glucuronide were made using the Wilcoxon rank sum test. This demonstrated significant suppression of both LH and FSH. Pregnanediol glucuronide, however, did not demonstrate a significant decline, strongly implying an adrenal source of the enhanced excretion. The decreased pregnanediol glucuronide noted in age-appropriate menopausal women compared with premature ovarian failure is likely to be a reflection of adrenal ageing.
Adrenal Glands↗
Rapid measurement of urinary pregnanediol glucuronide to diagnose ectopic pregnancy.
We investigated the ability of a single, random, urinary pregnanediol-3 alpha-glucuronide level to differentiate early intrauterine from ectopic pregnancy. Thirty-four patients with intrauterine gestations were compared with 60 patients with ectopic pregnancies. Urinary pregnanediol-3 alpha-glucuronide was measured by radioimmunoassay and enzyme immunoassay. Compared with intrauterine gestations, results demonstrate that urinary pregnanediol-3 alpha-glucuronide is significantly depressed in ectopic pregnancies: 24.5 +/- 2.2 versus 4.8 +/- 0.7 micrograms/ml (p = 0.0001). Urinary pregnanediol-3 alpha-glucuronide levels obtained by conventional radioimmunoassay correlated closely with values measured in minutes with enzyme immunoassay (r = 0.95, p = 0.0001), and with serum progesterone (r = 0.74, p = 0.0001). Urinary pregnanediol-3 alpha-glucuronide measured by enzyme immunoassay exhibited predictive values for detecting ectopic gestations comparable with random serum progesterone or serum beta-human chorionic gonadotropin values. We conclude that ectopic gestations demonstrate a reduced level of urinary pregnanediol-3 alpha-glucuronide (55/60 cases) detectable with a rapid enzyme immunoassay, which makes this assay a practical screening test in early pregnancy.
Chorionic Gonadotropin↗
Selective actions of certain neuroactive pregnanediols at the gamma-aminobutyric acid type A receptor complex in rat brain.
Certain endogenous pregnanediols (5 alpha-pregnan-3 alpha,20 alpha-diol and 5 beta-pregnan-3 alpha,20 beta-diol) were observed to have limited efficacy as allosteric modulators of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding to sites on the gamma-aminobutyric acid (GABA)A receptor complex in rat brain. In contrast, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-P) and 3 alpha-hydroxy-5 beta-pregnan-20-one (3 alpha,5 beta-P) have full efficacy. Moreover, 3 alpha,5 beta-P but not 3 alpha,5 alpha-P recognizes high (nanomolar) and low (micromolar) affinity neuroactive steroid sites in these allosteric modulatory assays. The concentration-response curve for 3 alpha,5 alpha-P modulation of [35S]TBPS binding was shifted rightward in the presence of these pregnanediols and GABA. The maximum shift produced by these pregnanediols never exceeded the concentration-response curve obtained with 3 alpha,5 alpha-P alone in the absence of GABA. Additionally, neither 5 alpha-pregnan-3 alpha,20 alpha-diol nor 5 beta-pregnan-3 alpha,20 beta-diol had any effect on the site recognized by 3 alpha,5 alpha-P in the absence of GABA. The difference in the affinities of the two apparent sites (29 nM versus 152 nM in the presence and absence of GABA, respectively) recognized by 3 alpha,5 alpha-P is only approximately 5-fold. In contrast, the difference between the high (30 nM) and low (7 microM) affinity sites discriminated by 3 alpha,5 beta-P is > 200-fold. Thus, the selective interaction between the high affinity site recognized by 3 alpha,5 beta-P and these pregnanediols can be clearly observed. A saturating concentration of 5 beta-pregnan-3 alpha,20 beta-diol selectively eliminated the high affinity component recognized by 3 alpha,5 beta-P, whereas 5 alpha-pregnan-3 alpha,20 alpha-diol did not completely abolish the high affinity site. 5 alpha-Pregnan-3 alpha,20 alpha-diol recognized only a portion of the high affinity sites discriminated by 3 alpha,5 beta-P, relative to 5 beta-pregnan-3 alpha,20 beta-diol, whereas the two pregnanediols recognized a similar population of sites mediating 3 alpha,5 alpha-P inhibition of [35S]TBPS binding. Collectively, these studies provide evidence that the limited efficacy of certain pregnanediols as allosteric modulators of [35S]TBPS binding may be explained in part by selectivity for the high affinity site recognized by 3 alpha,5 beta-P.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
The value of urinary pregnanediol estimation for monitoring early pregnancies.
Urine samples from 76 pregnant women were tested for pregnanediol content during the first 6 weeks of pregnancy. Pregnanediol was measured by gas chromatography in 24-hour urine samples obtained once weekly from 76 randomly selected pregnant women 21, 28, 35, and 42 days after the last menstrual period. Pregnancy was ascertained by a positive hemagglutination inhibition test for human chorionic gonadotropin. In patients in whom the urinary pregnanediol content was less than 3 mg/24 hours the abortion rate was 81.5%, and 18.5% had normal pregnancies and births In patients whose pregnanediol content was greater than 3 mg/24 hours the abortion rate was 8.3%, and 91.7% had normal pregnancies and births. The 24-hour urinary pregnanediol excretion rate reflects corpus luteum function and can be considered as a means of monitoring pregnancy in its initial stage.
Chromatography, Gas↗
Definition of the potentially fertile period from urinary steroid excretion rates. Part II. A threshold value for pregnanediol glucuronide as a marker for the end of the potentially fertile period in the human menstrual cycle.
Application of time series analysis to a database containing serial pregnanediol data from 113 complete ovulatory menstrual cycles contributed by 83 women of proven fertility and 68 cycles for which pregnanediol values were available over the ovulatory period, detected the first statistically significant risk in pregnanediol excretion for all cycles for which a baseline was available (n = 170). However, even at the 99% confidence level, for 22% of cycles a rise was observed before the presumed day of ovulation. Therefore, a threshold value for pregnanediol was sought from the database as a better marker for the end of fertility. A value of 1.4 mg per 24 h was not reached before day 2 after the pre-ovulatory estrogen peak day for 96% of the cycles. In the remaining 4% of cycles it was reached one day after the total estrogen peak day. The validity of this threshold was confirmed in extensive studies using the Ovarian Monitor where the equivalent is 6.3 mumol per 24 h of pregnanediol glucuronide and measurements are performed on timed urine specimens with a minimum collection time of three hours. These studies were as follows: 1) a World Health Organization study on the use of the Ovarian Monitor as a fertility self test in the home (108 cycles), 2) a multicenter study on returning fertility during breast feeding conducted by Family Health International (73 women), and 3) the general application of the Ovarian Monitor for pregnancy achievement and avoidance during the past ten years (over 250,000 PdG assays performed in ten countries). With rare exceptions, the use of these threshold values is applicable for all women provided correction is made for urine volume.
Biomarkers↗
Relationship of pregnanediol level to cognitive behavior and mood.
This work examines data secured from a larger study relating cognitive behavior and mood in women to variation in estrogen level. The larger study noted that performance tended to be better during the luteal phase. The present analysis looks at the relationship of urinary pregnanediol levels with mood and cognitive behaviors. Thirty women with non-oral contraceptive-controlled menstrual cycles were tested during the luteal phase on a battery of cognitive tests and a variation of the Clyde Mood Scale. The cognitive tests were selected based upon the automatization versus perceptual restructuring dimensions described by Broverman and colleagues. Pregnanediol levels were measured in 24-hour urine specimens collected on the same day. Results show a significant relationship of pregnanediol level with mental subtraction and with time estimation. Perceptual restructuring tasks in general (perceptual restructuring index) showed a significant positive relationship with pregnanediol levels. Mood, however, was not found to be related to pregnanediol levels.
Adult↗
Identification and measurement of urinary estrone, estradiol-17 beta, estriol, pregnanediol and androsterone during the menstrual cycle of the orangutan.
Urinary estrone, estradiol-17beta, estriol, pregnanediol and androsterone were identified and measured during 3 menstrual cycles in 2 female orangutans. In 2 of the cycles, the animals excreted 1-8 mug/day estrone, 0.5-6 mug/day estradiol-17beta, 1-8 mug/day estriol, 20-206 mug/day pregnanediol and 120-522 mug/day androsterone during the first half of the menstrual cycle. In the second half of the cycle, corresponding values were 3-21 mug/day estrone, 2-10 mug/day estradiol-17beta, 1-9 mug/day estriol, 54-800 mug/day pregnanediol and 90-1158 mug/day androsterone. In 1 cycle, the estrogen values for the second half were considerably higher, possibly due to the animal becoming pregnant just before this study commenced. The values for estrone and estradiol-17beta are similar to those found in the human and chimpanzee menstrual cycle. The values for estriol were lower than in the human but higher than in the chimpanzee. Levels for urinary pregnanediol and androsterone were significantly lower than in the human. Variations during the menstrual cycle for estrone were characterized by a midcycle peak followed by a second peak in the luteal phase. No definite pattern was apparent for estradiol-17beta or estriol. Both urinary pregnanediol and androsterone levels were low during the first half of the cycle, started to rise just after midcycle, and showed a peak during the second half of the menstrual cycle.
Androsterone↗
[The urinary excretion of pregnanediol during pregnancy determined by gas-liquid chromatography. I. Its evolution throughout the normal and pathological pregnancy (author's transl)].
Employing the technique described by Van Kampen and Anker, modified by Macarulla et al., 180 pregnant women have been studied (66 normals and 114 with different pathology: infertility, toxemia, diabetes, Rh isoinmunization, gemelar pregnancy and abortions), taking 319 determinations of pregnanediol in 24 hours urine samples. The analysis of the results show in normal pregnancy a progressive increase of the urinary pregnanediol from the beginning of gestation, this increase being more intense from the 20th week, reaching the maximum value in the 37th week and from this point descending slowly. In patients with toxemia, the values of pregnanediol (in the majority of the cases) are decreased, while in pregnant women with antecedents of infertility are increased from the 36th week of pregnancy, although they had protective treatment from first months of pregnancy. No manifest deviations of urinary pregnanediol from the normal values exist in diabetic pregnant women, Rb isoinmunization or gemelar pregnancies. In aborted pregnancies the pregnanediol values are markedly decreased without a tendency to increase, contrary to the threats of abortion in full-term pregnancies.
Chromatography, Gas↗
Anxiolytic properties of endogenously occurring pregnanediols in two rodent models of anxiety.
Certain endogenously occurring 3 alpha-hydroxylated, 5-reduced pregnane steroids act at a specific site on the GABAA receptor complex (GRC) to modulate the effects of GABA at its receptor. Modulators that potentiate GABA at the GABAA receptor often possess anxiolytic properties. The anxiolytic potential of four 5-reduced, 3 alpha, 20-pregnanediols, differing only in the stereochemical orientation of the steroid A-ring and the 20-hydroxyl group, were tested in the Vogel test following intracerebroventricular (ICV) administration. The effects of these pregnanediols were compared to those of their 20-ketone analogues, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha, 5 alpha-P) and 3 alpha-hydroxy-5 beta-pregnan-20-one (3 alpha, 5 beta-P). All four pregnanediols tested significantly enhanced punished drinking at doses ranging from 10 to 60 micrograms. The rank order of potency based on the minimum effective dose (MED) observed was 5 alpha-pregnan-3 alpha,20 alpha-diol = 5 beta-pregnan-3 alpha,20 alpha-diol > 5 beta-pregnan-3 alpha,20 beta-diol > 5 alpha-pregnan-3 alpha, 20 beta-diol. 3 alpha,5 beta-P and 3 alpha,5 alpha-P enhanced punished responding when administered at 2.5 and 5 micrograms, respectively. 3 beta,5 alpha-P which is inactive at the GRC was also inactive (up to 100 micrograms) in the Vogel test. The benzodiazepine control diazepam was efficacious when administered at 2.5 micrograms. 5 alpha-Pregnan-3 alpha,20 alpha-diol was further tested in the mouse elevated plus-maze model following systemic administration where it was found to be active in a dose range of 10-40 mg/kg IP. These results raise the possibility that in addition to 3 alpha,5 alpha-P and 3 alpha,5 beta-P, some of their endogenously occurring pregnanediol metabolites may also influence physiological processes related to anxiety via the GRC.
Animals↗
Characterization of luteal function by measuring the cumulative concentration of serum progesterone and urine pregnanediol-3 alpha-monoglucuronide.
The corpus luteum function of healthy, fertile women was established by measuring the serum progesterone and the early-morning urine pregnanediol-3 alpha-monoglucuronide levels during the ovulation cycles. Integration of the results led to a parameter, the luteal index (Ll), which represents the overall hormone production that characterizes the luteal function quantitatively much better than the criteria used so far. The average of the integrated hormone concentrations (Ll) for progesterone and pregnanediol were 451.4 nmol/l X time and 151.3 mumol/l X time respectively. Statistical analyses show that values of luteal index below 348.9 nmol/l X time progesterone and 134.5 mumol/l X time pregnanediol can be regarded, with very high probability, as symptomatic of luteal dysfunction. The course of the production of both progesterone and pregnanediol is characterized. The importance of these parameters in functional infertility is discussed.
Adult↗
Development of a direct microplate enzyme immunoassay for the determination of pregnanediol-3 alpha-glucuronide in urine.
A sensitive direct enzyme immunoassay for urine pregnanediol-3 alpha-glucuronide was developed. The assay system involves the use of an antiserum against pregnanediol-3 alpha-glucuronide and an enzyme-labelled antigen chemically prepared by linking beta-D-galactosidase to 20 alpha-hydroxy-5 beta-pregnane 3(O-carboxymethyl)oxime. Free from antibody-bound antigen was separated by a solid-phase double antibody method, using a microplate coupled with goat anti-rabbit gamma-globulin. This solid-phase enzyme immunoassay for urine pregnanediol-3 alpha-glucuronide was validated in terms of specificity, accuracy and sensitivity. When urine samples were assayed for pregnanediol-3 alpha-glucuronide, the results obtained by the solid phase enzyme immunoassay and conventional radioimmunoassay methods agreed well (n = 30, r = 0.922). This assay system has an advantage over radioimmunoassay, because it does not require the use of radioisotopes. The procedure of this method is very simple, since it does not require purification steps of the biological samples.
Female↗
Use of monoclonal antibodies to pregnanediol-3 alpha-glucuronide for the development of a solid phase chemiluminescence immunoassay.
Monoclonal antibodies to pregnanediol-3 alpha-glucuronide were produced by hybridomas between P3-X63-Ag8 variants and spleen cell of mice immunized with a bovine serum albumin conjugate of the homologous hapten. The ascites fluid collected from mice inoculated with the cloned hybridoma cells contained antibodies with high specificity and affinity to pregnanediol-3 alpha-glucuronide. A sensitive solid-phase chemiluminescence immunoassay for urinary pregnanediol-3 alpha-glucuronide was established utilizing these antibodies. The assay was validated in terms of specificity, accuracy, sensitivity and precision. When urine samples were assayed for pregnanediol-3 alpha-glucuronide, the results obtained by the solid-phase chemiluminescence immunoassay method and the conventional gas liquid chromatographic method agreed well (n = 30, r = 0.96). The method may be of value for monitoring luteal function since it is fast, sensitive and does not require the use of radioisotopes or purification of the biological sample. Monoclonal antibody preparations facilitate rigorous standardization of the assay.
Animals↗