Urinary vitamin D-binding protein as a marker of ovarian reserve.

BACKGROUND: Ovarian reserve reflects the quality and quantity of available oocytes and has become an indispensable measure for the better understanding of reproductive potential. Proteomic approaches are especially helpful in discerning differential protein expression patterns associated with normal and diseased states and, thus, proteomic analyses are increasingly used to identify clinically useful biomarkers. The aim of this study was to investigate proteins secreted in the urine of patients with different ovarian reserve by proteomic techniques to identify potential markers for assessing ovarian reserve. METHODS: Urine samples were obtained from patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), and from normal control (NC)participants. We used isobaric tags for relative and absolute quantification (iTRAQ) technology combined with mass spectrometry analysis to identify candidate urinary proteins in the three groups. The selected proteins were confirmed using western blot analysis and enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic analysis. RESULTS: When Compared with NC samples, 285 differentially expressed proteins (DEPs) were identified in the DOR samples and 372 in the PCOS samples. By analyzing the intersection of the two groups of DEPs, we found 26 proteins with different expression trends in the DOR and PCOS groups. Vitamin D-binding protein (VDBP) was the key protein for the protein-protein interaction network. ELISA quantification of urinary VDBP revealed the highest levels in the PCOS group, followed by the NC group and the lowest levels in the DOR group (115.90 ± 26.02, 81.86 ± 23.92 and 52.84 ± 21.37 ng/ml, respectively; P < 0.05). As a diagnostic marker, VDBP had a sensitivity of 67.4% and a specificity of 91.8% for DOR, and a sensitivity of 93.8% and a specificity of 77.6% for PCOS. CONCLUSIONS: Urinary VDBP is closely associated with ovarian reserve and can be considered as a novel noninvasive biomarker of ovarian reserve. However, studies including large sample sizes are needed to validate these results.

Hyperprolactinemic African elephant (Loxodonta africana) females exhibit elevated dopamine, oxytocin and serotonin concentrations compared to normal cycling and noncycling, low prolactin elephants†.

Many zoo elephants do not cycle normally, and for African elephants, it is often associated with hyperprolactinemia. Dopamine agonists successfully treat hyperprolactinemia-induced ovarian dysfunction in women, but not elephants. The objective of this study was to determine how longitudinal dopamine, serotonin, and oxytocin patterns in African elephants are related to ovarian cycle function. We hypothesized that dopamine concentrations are decreased, while oxytocin and serotonin are increased in non-cycling, hyperprolactinemic African elephants. Weekly urine and serum samples were collected for eight consecutive months from 28 female African elephants. Females were categorized as follows: (1) non-cycling with average prolactin concentrations of 15 ng/ml or greater (HIGH; n = 7); (2) non-cycling with average prolactin concentrations below 15 ng/ml (LOW; n = 13); and (3) cycling with normal progestagen and prolactin patterns (CYCLING; n = 8). Both oxytocin and serotonin were elevated in hyperprolactinemic elephants. Thus, we propose that stimulatory factors may play a role in the observed hyperprolactinemia in this species. Interestingly, rather than being reduced as hypothesized, urinary dopamine was elevated in hyperprolactinemic elephants compared to CYCLING and LOW prolactin groups. Despite its apparent lack of regulatory control over prolactin, this new evidence suggests that dopamine synthesis and secretion are not impaired in these elephants, and perhaps are augmented.

[Strategies in laboratory medicine for the endocrinological diagnosis of ovarian disorders]. / Laboratoriumsmedizinische Strategien in der endokrinologischen Diagnostik ovarieller Störungen.

The endocrine laboratory analyses are essential for an adequate diagnosis and therapy of many ovarian pathologies. This article portrays this fact for four gynecological disorders. The endocrinological strategies for diagnosing secondary amenorrhoea, female infertility enclosing the polycystic ovarian syndrome, perimenopause and endocrine active ovarian tumors are highlighted in its main features.

False-positive urine beta-HCG in a woman with a tubo-ovarian abscess.

Modern urine beta-human chorionic gonadotropin (HCG) assays that use enzyme-linked immunosorbent assay (ELISA) technology are sensitive and specific for diagnosing pregnancy, both intrauterine and ectopic, and have become indispensable to the practice of Emergency Medicine. A urine HCG test is often relied on by the Emergency Physician as a critical component in the diagnostic regimen of a patient with a possible ectopic pregnancy. We report a case of a false-positive urine beta-HCG test in a patient with a ruptured tubo-ovarian abscess. Though false-positive pregnancy tests with tubo-ovarian abscesses have previously been reported with older methods of HCG detection, we believe that this is the first case where the pregnancy test was the modern ELISA type. The mechanism for the false-positive reaction in this case is unknown, but time may show that the ELISA test kit, like its predecessors, may occasionally give a false-positive reaction in this class of patients.

Correlation of serum, urinary and salivary CA 125 levels in patients with adnexal masses.

A prospective study was made of 105 consecutive patients admitted to one department of obstetrics and gynaecology for surgery for adnexal masses. The objective was to investigate if CA 125 level is measurable in the urine or saliva and to correlate these measurements with serum CA 125 level in patients presenting with adnexal masses. The final diagnosis and grouping of patients for analysis were based on histopathological examination of the adnexal masses. Serum, urine and salivary samples were collected simultaneously from all patients on the morning before surgery. CA 125 levels in each sample were determined in duplicate using Abbott CA 125-E1A monoclonal test kits (Abbott Laboratories, USA). The mean inter-assay variability was 10%. CA 125 was detectable in the serum, urine and saliva from all the patients and the concentration was highest in the saliva and lowest in urine. There were no discernible differences in the distributions of salivary CA 125 concentrations between patients with ovarian malignancies and those with benign ovarian cysts. In contrast, both serum and urinary CA 125 levels were significantly higher in the ovarian cancer group. There was no correlation in CA 125 concentrations between serum and urine, or between serum and saliva. For detection of ovarian malignancies, the sensitivity, specificity, and positive and negative predictive values for serum CA 125 measurement (> or = 35 U/mL) were 88.9%, 79.2%, 27.6% and 98.7 respectively. The corresponding figures for urinary CA 125 measurement (> or = 10 U/mL) were 88.9%, 66.7%, 19.5% and 98.4% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary cholesterol. VII. The significance of the excretion of nonesterified cholesterol in patients with uterine carcinomas.

The urinary excretion of nonesterified cholesterol (NEC) in 170 women with cervical and endometrial carcinomas has been investigated. Control patients (236) included: 1) women with other types of (benign and/or malignant diseases of the pelvic organs; 2) patients with non-steroid-related neoplasms; 3) patients with benign and/or malignant breast diseases other than carcinoma; and 4) patients with a variety of non-neoplastic diseases. NEC was determined by a gas-liquid chromatographic procedure. The range of NEC excretion for clinically healthy normal women (64) was previously established by this method. NEC hyperexcretion was defined as any NEC value over 1.5 mg/24 hours. The results showed NEC hyperexcretion in 65 of 68 women with active carcinoma of the cervix, including 13 patients with carcinoma in situ, and in 42 of 45 women with active carcinoma of the endometrium. In contrast, a normal excretion of NEC occurred in all the patients (77) of the first and second control groups, in 39 (80%) of the 48 patients of the third control group (high-risk group), and in 101 of the 111 patients of the fourth control group. Sequential studies performed in patients with uterine carcinomas have demonstrated an almost perfect correlation between the NEC excretion and the clinical status of the patient following surgical and/or radiation therapy. Of 57 patients (31 cervix and 26 endometrium) in which the NEC studies were started after treatment was instituted, 53 have normal NEC excretion in the multiple determination performed to date. Presently these patients have no clinical, chemical, or radiologic evidence of cancer. It is concluded that urinary NEC determination can be used as an additional diagnostic biochemical test to detect active carcinoma of the steroid-producing glands and their main target organs, and that in women with uterine carcinomas, the test can be used as an objective laboratory method to monitor the course of the disease and the response of the patient to therapy.

The investigation of ovarian function by measurement of urinary oestrogen and pregnanediol excretion.

Urinary oestrogen and pregnanediol excretion was measued daily ("daily monitoring") for a complete cycle in 20 normally menstruating women, in one patient with an anovulatory cycle and for 28 days in a patient with secondary amenorrhoea. The measurements were also performed on urine specimens collected at weekly intervals for 4 to 6 weeks ("weekly tracking") from 506 patients with evidence of abnormal ovarian function. These included 9 patients with primary amenorrhoea, 132 patients with secondary amenorrheoa, 138 patients with oligomenorrhoea and 227 patients with evidence of ovarian dysfunction and cycle lengths of 25 to 42 days. The results were subjected to statistical analysis. In the normal cycles, ovulation could be identified on the criteria of a rising pregnanediol value reaching or exceeding 2-0 mg. per 24 hours for a period of 7 days or more. Valid conclusions on the overall mean oestrogen and pregnanediol values for a complete cycle could be made from the results of weekly tracking, irrespective of which day the tracking commenced. Correlations were obtained by comparing the mean and maximum urinary oestrogen values and the variability of the values with the evidence of ovarian function indicated by the clinical classifications of the patients, the duration of the disorders and the subsequent occurrence of uterine bleeding. Mean oestrogen values of 10 mug. per 24 hours or less were associated with lack of ovarian function. For values higher than this a discriminant function based on both the mean oestrogen value and the variability of the oestrogen values was useful in predicting onset of spontaneous menstruation. A single urine specimen collected 4 to 8 days before onset of menstruation showing a raised pregnanediol value of 2-0 mg. per 24 hours or more provided a valid test for ovulation in women with regular cycles, and a single urine specimen giving an oestrogen value of 10 mug per 24 hours or less gave a valid indication of absent ovarian function in women with amenorrhoea for two years or more. In all other circumstances serial sampling at weekly intervals provided a valid assessment of ovarian activity. Application of these principles allows the greatest amount of information on ovarian function to be obtained with the greatest economy of effort.