Impact of macroprolactin on galactorrhea and the rate of patients possibly affected by macroprolactin.

The clinical influence of macroprolactin (MPRL) is not clearly understood and the rate of patients potentially affected by MPRL is unknown. We investigated the influence of MPRL on the onset of galactorrhea and estimated the rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea. Data of patients with obstetric or gynecological symptoms who had undergone PRL fractionation testing were retrospectively analyzed. To evaluate factors influencing galactorrhea, a multivariate logistic regression analysis was performed and the adjusted odds ratios of MPRL for galactorrhea were calculated. Cutoff values for the total PRL level and the proportion of MPRL fractions for galactorrhea were determined by ROC analysis using a multivariate logistic model. The prevalence of patients with a proportion of MPRL fraction greater than or equal to the cutoff value for galactorrhea was estimated. The median proportion of MPRL fraction was 30.1% and increased as PRL level increased. Total PRL and MPRL had a significant influence on the onset of galactorrhea and the adjusted odds ratio was 1.09 in total PRL and 0.94 in MPRL. The rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea was estimated to be 33.5% of the study population, and thus found to be twelve times or more the number of macroprolactinemia patients. Future prospects for hyperprolactinemia may require diagnostic criteria using free prolactin levels and so MPRL fraction measurement is important for the diagnosis and treatment of patients with obstetric and gynecological symptoms.

Evaluation of Total, Active, and Specific Myeloperoxidase Levels in Women with and without Endometriosis.

Myeloperoxidase (MPO) is a proinflammatory enzyme and a marker for neutrophil activation and oxidative stress. Since oxidative stress and inflammation are linked to the pathogenesis of endometriosis, we hypothesized that the total, active, and specific (active/total) MPO levels were significantly different in plasma of women with and without endometriosis. Samples were selected from our biobank from women with endometriosis (n = 212) and controls without endometriosis (n = 121) across the menstrual cycle. Total MPO plasma levels were measured by immunoassay and MPO activity by enzymatic assay. Total and active MPO levels did not differ significantly among endometriosis cases and controls, whereas the specific MPO activity was significantly lower in women with endometriosis than that in controls (p = 0.0159). After the subdivision of control patients into women with a normal pelvis and women with other benign gynecological disorders, a significant difference was observed only between women with endometriosis and women with other benign gynecological disorders (p = 0.0266). In conclusion, systemic MPO levels may not be suited as a single biomarker for endometriosis. Our data support the involvement of MPO in other gynecological disorders but do not provide any evidence for an association with endometriosis.

[The influence of the comprehensive spa and health resort-based treatment on the system of hormonal regulation in the women presenting with gynecological pathology depending on the plasma prolactin level]. / Vliianie kompleksnogo sanatorno-kurortnogo lecheniia na sistemu gormonal'noi reguliatsii u zhenshchin s ginekologicheskoi patologiei v zavisimosti ot urovnia prolaktina.

AIM: The objective of the present study was to evaluate the influence of the comprehensive spa and health resort-based treatment on the system of hormonal regulation in the women presenting with bacterial vaginosis and concomitant chronic inflammatory diseases of the pelvic organs depending on the plasma prolactin level. MATERIAL AND METHODS: We investigated the indicators of hormonal regulation in 186 women suffering from bacterial vaginosis and concomitant chronic inflammatory diseases of the pelvic organs depending on the level of prolactin in blood plasma. The first group consisted of 128 women with the normal plasma prolactin levels whereas the second group was comprised of 58 women having hyperprolactinemia. The relevant laboratory data were obtained before and after peloid therapy. RESULTS: The application of the therapeutic peloids for the treatment of the women presenting with the normal level of prolactin in blood plasma was shown to contribute to the positive clinical dynamics of the patients' condition and have a modulating effect on the level of pituitary hormones as well as a stimulating effect on the function of the ovaries. The peloid therapy given to the women with hyperprolactinemia exacerbates the hormonal imbalance as a result of the increase of the initial level of prolactin, discoordination of the hormonal regulation at the level of the pituitary-ovarian system, and enhancement of the adrenal gland function regardless of the level of prolactin. CONCLUSION: The results of the study give evidence of the possibility to use the plasma prolactin level as an indicator of the effectiveness of the spa and health resort-based treatment of the women presenting with gynecological pathology. Moreover, they suggest the necessity of a differentiated approach to the application of the therapeutic peloids for the treatment of gynecological patients with the disturbances of the hormonal regulation taking into consideration the initial level of prolactin in the blood plasma and the presence of hyperprolactinemia prior to the prescription of the spa and health resort-based treatment including peloid therapy.

Antioxidant status in blood of gynaecological patients: influence of diagnosis and reproductive factors.

Cancer of the reproductive tract is an important cause of morbidity and mortality among women worldwide. In this study we evaluated the influence of diagnostic categories, age and reproductive factors on antioxidant enzymes and lipid hydroperoxides in the blood of gynaecological patients diagnosed with endometrial polyp, myoma, hyperplasia simplex, hyperplasia complex and endometrial adenocarcinoma. Multivariate regression analysis was used to assess the association of diagnosis, age, parity, abortions and abnormal uterine bleeding with the examined parameters. Diagnosis provided the best predictive model for superoxide dismutase, catalase and glutathione peroxidase activities, and also for the lipid hydroperoxide level. Abortions fitted the best predictive model for superoxide dismutase activity. A significant correlation was also found between the predictor variables themselves. This study showed that reproductive and other factors may be associated, at least partially, with antioxidant capacity and ability to defend against the oxidative damage in gynaecological patients with various diagnoses.

Increased human epididymis protein 4 in benign gynecological diseases complicated with chronic renal insufficiency patients.

We examined the serum concentration of human epididymis protein (HE4) in patients with benign gynecological diseases complicated with chronic renal deficiency and its significance in the differential diagnosis of benign and malignant gynecological diseases. Serum HE4 and cancer antigen 125 concentrations were detected by chemiluminescence. Clinically or pathologically confirmed gynecological diseases were grouped and retrospectively analyzed, including 50 cases of gynecological benign diseases, 35 cases of non-mucinous epithelial ovarian carcinoma, 36 cases of endometrial adenocarcinoma, 15 cases of gynecological benign diseases patients complicated with chronic renal deficiency, 15 cases of gynecological diseases without chronic renal deficiency, and 30 normal controls. Serum HE4 values in the ovarian cancer group, endometrial cancer group, gynecological benign diseases with chronic renal deficiency group, and chronic renal deficiency group were significantly increased compared with the benign gynecological diseases and normal control groups, showing a significant difference (P < 0.001). A comparison of 4 groups with high HE4 showed that the HE4 level in the 2 groups with renal deficiency were higher than those in the ovarian cancer and endometrial cancer groups, but the difference was not significant (P > 0.05); there was no significant difference between 2 groups with renal deficiency (P > 0.05). Serum concentration of HE4 was high in patients with chronic renal deficiency, which should be distinguished during differential diagnosis of gynecological benign and malignant tumors in patients with chronic renal deficiency to avoid misdiagnosis.

HE4, Ca125 and ROMA algorithm for differential diagnosis between benign gynaecological diseases and ovarian cancer.

The aim of this study is to evaluate the diagnostic performance of human epididymis protein 4 (HE4), cancer antigen 125 (Ca125) and the risk of ovarian malignancy algorithm (ROMA) in discriminating ovarian cancer from other benign gynaecological diseases. Serum levels of HE4 and Ca125 were measured in 119 women with benign gynaecological diseases, 29 patients with primary ovarian cancer, 32 patients with ovarian cancer on chemotherapy treatment (18 of them with progressive disease), 6 patients treated and free of disease and 32 healthy women. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios (LR ±) were calculated. Receiver operator characteristic (ROC) curves were constructed, and the areas under the curve (AUC) were calculated. High serum levels for HE4, Ca125 and ROMA were observed in cancer patients. HE4 was elevated in 12.6 %, Ca125 in 21 % and ROMA in 9.2 % in the benign group, but HE4 was not elevated in endometriosis. The AUC values for HE4, Ca125 and ROMA were 0.92, 0.911 and 0.945 respectively. The sensitivity for discriminating ovarian cancer from benign gynaecological diseases was 86.2 % for HE4 and Ca125 and 93.1 % for ROMA. The specificity was 87.4, 78.9 and 90.7 % for HE4, Ca125 and ROMA. The overall positive likelihood ratio (LR+) was 6.84 for HE4, 4.1 for Ca125 and 10.01 for ROMA. In premenopausal women, LR + was 11.86 for HE4, 5.11 for ROMA and 2.02 for Ca125. HE4 might be significant in the differential diagnosis of ovarian cancer. HE4 seems to be superior to Ca125 in terms of diagnostic performance of all premenopausal women. ROMA could help to discriminate in cases with any doubt with a high diagnostic accuracy.

Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders.

OBJECTIVE: The human epididymis protein 4 (HE4) is a novel biomarker for ovarian cancer. This study measured the HE4 and CA125 levels in women with benign gynecological disorders. STUDY DESIGN: Sera were obtained from women prior to surgery for a pelvic mass and HE4 and CA125 levels were determined. The proportions of patients with elevated biomarker levels were compared. RESULTS: There were 1042 women with benign disease. HE4 levels were less often elevated than CA125 (8% vs 29%, P < .001). A marked difference was observed in patients with endometriosis in which HE4 was elevated in 3% of patients and CA125 in 67% (P < .0001). Serous ovarian tumors were associated with elevated levels of HE4 in 8% of patients and CA125 in 20% (P = .0002); uterine fibroids in 8% vs 26% (P = .0083); dermoids in 1% vs 21% (P = .0004); and inflammatory disease in 10% vs 37% (P = .014). CONCLUSION: HE4 is elevated less frequently than CA125 in benign disease, particularly in premenopausal patients.

The investigation of ABO and Rh blood groups distribution in patients with endometriosis needs new project design.

We carefully studied all the three published papers in your journal as "ABO and Rh Blood group distribution in patients with endometriosis" and "Associations of ABO blood groups with various gynecologic diseases" and would like to express our point of view about them.

HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases.

The aim of this study is to evaluate a new tumour marker, HE4, in comparison with CA 125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in healthy women and in patients with benign and malignant gynaecological diseases. CA 125 and HE4 serum levels were determined in 66 healthy women, 285 patients with benign gynaecological diseases (68 endometriosis, 56 myomas, 137 ovarian cysts and 24 with other diseases), 33 patients with non-active gynaecological cancer and 143 with active gynaecological cancer (111 ovarian cancers). CA 125 and HE4 cut-offs were 35 U/mL and 150 pmol/L, respectively. ROMA algorithm cut-off was 13.1 and 27.7 for premenopausal or postmenopausal women, respectively. HE4, CA 125 and ROMA results were abnormal in 1.5%, 13.6% and 25.8% of healthy women and in 1.1%, 30.2% and 12.3% of patients with benign diseases, respectively. Among patients with cancer, HE4 (in contrast to CA 125) had significantly higher concentrations in ovarian cancer than in other malignancies (p < 0.001). Tumour marker sensitivity in ovarian cancer was 79.3% for HE4, 82.9% for CA 125 and 90.1% for ROMA. Both tumour markers, HE4 and CA 125 were related to tumour stage and histological type, with the lowest concentrations in mucinous tumours. A significantly higher area under the ROC curve was obtained with ROMA and HE4 than with CA 125 in the differential diagnosis of benign gynaecological diseases versus malignant ovarian cancer (0.952, 0.936 and 0.853, respectively). Data from our population indicate that ROMA algorithm might be further improved if it is used only in patients with normal HE4 and abnormal CA 125 serum levels (cancer risk for this profile is 44.4%). ROMA algorithm in HE4 positive had a similar sensitivity and only increases the specificity by 3.2% compared to HE4 alone.

Human epididymis protein 4 (HE4) as a serum tumor biomarker in patients with ovarian carcinoma.

BACKGROUND: Ovarian cancer remains a leading cause of death from gynecological malignancy. Early diagnosis is the most important determinant of survival. For more than 25 years, cancer antigen 125 (CA 125) has been the criterion standard biomarker for the diagnosis and management of women with epithelial ovarian cancer. This study evaluated human epididymis protein 4 (HE4), a novel ovarian cancer biomarker, both alone and in combination with CA 125 as a diagnostic marker for ovarian cancer in a Chinese population. METHODS: Sera from 491 Chinese women with ovarian cancer or nonmalignant disorders and healthy women were analyzed. Sensitivities and specificities for both biomarkers and the combination were determined using predefined cutoffs (HE4>150 pmol/L and CA 125>35 U/mL) and receiver operator characteristic curves to define cutoffs based on 95% and 98% sensitivities. RESULTS: At baseline, serum HE4 and CA 125 levels were significantly higher in the ovarian cancer group versus the 5 reference groups. Using predefined cutoffs, HE4 specificity for ovarian cancer ranged from 90% to 100%; CA 125 specificity ranged from 36% (benign gynecologic disease) to 99%. Combining both markers yielded specificity for ovarian cancer of 100%. Using receiver operator characteristic curve analysis, the cutoff for 95% and 98% specificity was 102.6 and 150.2 pmol/L for HE4, respectively, and 127.2 and 325.5 U/mL for CA 125, respectively; the sensitivity of CA 125 for distinguishing ovarian cancer from benign gynecologic disease was 54% (95% specificity) and 28% (98% specificity), improving to 78% and 68%, respectively, with the addition of HE4. CONCLUSIONS: Human epididymis protein 4 used in conjunction with CA 125 yields improved specificity for ovarian cancer compared with the use of CA 125 alone, generally similar to results seen in non-Chinese populations.

Highly elevated serum CA-125 levels in patients with non-malignant gynecological diseases.

PURPOSES: To identify patients with highly elevated serum CA-125 levels and analyze their clinical characteristics. METHODS: Patients with non-malignant gynecologic disease (NMGDs, n = 41), in whom serum CA-125 levels were over 1,000 IU/ml were retrospectively enrolled in the study. Seventy-one patients with epithelial ovarian cancer (EOC), in whom, serum CA-125 levels were over 1,000 IU/ml were included as the comparison group. Clinical parameters were compared between the two groups. RESULTS: In NMGDs group, 43.90% of the patients had endometriosis. The median of serum CA-125 level in NMGDs was much lower than that of EOC subjects (P < 0.001). Compared to EOC group, the patients in NMGDs group were much younger (P < 0.001) and had fewer histories of pelvic masses (P < 0.001) but had more clinical complaints such as acute abdominal symptoms (P < 0.001) and/or abnormal vaginal bleeding (P = 0.022). Clinical progresses of these two groups were correlated with changes of serum CA-125 levels by follow-up for up to 386 days. CONCLUSIONS: High levels of serum CA-125 were found not only in the EOC, but also in some NMGDs, especially in the reproductive patients with complaints of acute abdomen symptoms or abnormal vaginal bleeding.

The presence of CD40, CD40L and ADAM8 among endometriotic patients.

Clinical and molecular research data are still insufficient to determine the onset, etiology and progression of endometriosis. Recently, a number of studies have been investigating the role of the inflammatory-immune factor. The role of inflammation in tissue infiltration and staging of endometriosis is limited. The aim of this study is to investigate the presence of CD40, CD40L and ADAM8 among endometriotic patients. These three markers of inflammation were measured in the serum of each of 76 women participating in the study. Twenty-nine (29) women, of mean age 36.9, (±9.2 SD) years free of endometriosis served as the control group. Of the endometriotic women 15 had a stage I-II and 32 stage III-IV disease. We undertook the present investigation expecting that an increased expression of CD40, CD40L and ADAM8 would testify to the inflammatory-autoimmune character of endometriosis. No difference in the levels of CD40, ADAM 8, CD40L was detected between the two groups. The stage of endometriosis did not affect CD40, ADAM 8, CD40L serum concentrations. A difficulty in our study is the lack of data with which to compare our results. Further investigation is needed to elucidate the role of these inflammatory markers in endometriosis.

Ischemia-modified albumin in gynecology.

Background: Ischemia-modified albumin (IMA) is an oxidative stress marker used to assess the presence and severity of oxidative stress. This marker was first used for early diagnosis of myocardial ischemia. Materials & methods: A variety of IMA studies were carried out to show the effect of oxidative stress on gynecological disorders. Conclusion: This analysis summarizes the literature by conducting electronic research on the relationship between IMA and gynecological disorders.

Endocrine Disorders and Genital Infections Impair Gynecological Health in APECED (APS-1).

Objective: In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) defects in the autoimmune regulator gene lead to impaired immunotolerance. We explored the effects of immunodeficiency and endocrinopathies on gynecologic health in patients with APECED. Design: Cross-sectional cohort study combined with longitudinal follow-up data. Methods: We carried out a gynecologic evaluation, pelvic ultrasound, and laboratory and microbiologic assessment in 19 women with APECED. Retrospective data were collected from previous study visits and hospital records. Results: The study subjects' median age was 42.6 years (range, 16.7-65.5). Sixteen patients (84%) had premature ovarian insufficiency, diagnosed at the median age of 16.5 years; 75% of them used currently either combined contraception or hormonal replacement therapy. In 76% of women, the morphology and size of the uterus were determined normal for age, menopausal status, and current hormonal therapy. Fifteen patients (79%) had primary adrenal insufficiency; three of them used dehydroepiandrosterone substitution. All androgen concentrations were under the detection limit in 11 patients (58%). Genital infections were detected in nine patients (47%); most of them were asymptomatic. Gynecologic C. albicans infection was detected in four patients (21%); one of the strains was resistant to azoles. Five patients (26%) had human papillomavirus infection, three of which were high-risk subtypes. Cervical cell atypia was detected in one patient. No correlation between genital infections and anti-cytokine autoantibodies was found. Conclusions: Ovarian and adrenal insufficiencies manifested with very low androgen levels in over half of the patients. Asymptomatic genital infections, but not cervical cell atypia, were common in female patients with APECED.

Disseminated intravascular coagulation in obstetric and gynecologic disorders.

Disseminated intravascular coagulation (DIC) is a syndrome characterized by a massive, widespread, and ongoing activation of the coagulation system, secondary to a variety of clinical conditions. Many obstetric complications, such as abruptio placentae, amniotic fluid embolism, endotoxin sepsis, retained dead fetus, post-hemorrhagic shock, hydatidiform mole, and gynecologic malignancies, might trigger DIC. In these gynecologic and obstetric settings, DIC is usually associated with high mortality and morbidity rates. No single laboratory test is sensitive or specific enough to diagnose DIC definitively, but it can be diagnosed by using a combination of multiple clinical and laboratory tests that reflect the pathophysiology of the syndrome. At present, the therapeutical approach to pregnancy- and gynecologic-related DIC comprises the specific and aggressive treatment of the underlying disease, eventually followed by a supportive blood product replacement therapy and restoration of physiological anticoagulant pathways. This article reviews the etiopathogenesis, clinical manifestations, laboratory diagnosis, and therapy of pregnancy- and gynecologic-related DIC.

The use of a novel ELISA method for detection of antibodies against p63 in sera from patients diagnosed with oral and/or genital and skin lichen planus.

Lichen planus is a chronic inflammatory disease of mucosa and skin affecting approximately 1-2% of the adult population. Autoimmunity has been implicated in the etiology of this disease, and recently we detected antibodies directed against all six p63 isoforms in sera from 2 out of 20 patients diagnosed with oral lichen planus (OLP) using Western blot analysis. Here we have developed an ELISA method for screening sera for presence of autoantibodies directed against p63. Using the same sera as previously analysed, we show that the optical density ratios for sera from the two patients with known autoantibodies was considerably higher compared to mean optical density ratios for all samples as well as controls analysed. Applying this novel ELISA technique for screening of sera from an additional group of 46 patients with oral and/or genital or skin lichen and 43 matched controls, we detected another three patients with autoantibodies against the p63 proteins. These data are discussed together with the observation that all five patients with detectable p63 autoantibodies from our two studies had clinically severe disease symptoms.

Serum vascular endothelial growth factor and adiponectin levels in patients with benign and malignant gynecological diseases.

INTRODUCTION: One of the most specific and critical regulators of angiogenesis is vascular endothelial growth factor (VEGF), which regulates endothelial proliferation, permeability, and survival. Vascular endothelial growth factor is an angiogenic mediator in tumors and has been implicated in the pathogenesis and progression of cancer. Adipose tissue is a major endocrine and it secretes hormones termed adipokines. These factors are derived from adipocytes and include proteins and metabolites such as adiponectin. Recently, adiponectin was also shown to modulate angiogenesis. This study was designed to determine the serum VEGF and adiponectin levels in patients with benign and malignant gynecological diseases and if there was a correlation between serum VEGF and adiponectin. METHODS: Serum samples, collected fasting before surgery or intervention, were available for total of 114 female patients recorded between October 2006 and December 2008. Diagnosis of benign and malignant gynaecological diseases was established by biopsy. Serum levels VEGF and adiponectin were using commercially available enzyme linked immunosorbent assay (R&D Systems Inc, Minneapolis, MN), respectively. Statistical analysis was performed by using the SPSS 9.0 software package (SPSS, Inc, Chicago, IL). The correlation between serum VEGF and serum Adiponectin was calculated using the Pearson correlation coefficient. P values of < 0.05 were considered statistically significant. RESULTS: Our results were analyzed on the basis of 2 different parameters: age and benign and malignant gynecological diseases of the patient. Only for serum VEGF levels was a significant difference observed (P = 0.004) between patients with benign and malignant gynecological diseases. A significantly inverse correlation between serum VEGF and adiponectin levels among patients with benign and malignant gynecological diseases was found. Adiponectin level is not correlated with body mass index. CONCLUSIONS: This is one of the first report on adiponectin in benign and malignant gynecological diseases. Future studies are needed to address the clinical potential role of adiponectin in cancer.

[Exploration of post-menopausal uterine bleeding. Hysteroscopy-histology correlation in 94 cases]. / Exploration des métrorragies postménopausiques par hystéroscopie : à propos de 94 cas.

INTRODUCTION: Post-menopausal uterine bleeding is the reason for nearly 70% of gynaecological consultations. Because the cause may be a malignant disease, a thorough work-up is necessary to attempt to identify an organic cause. PATIENTS AND METHODS: This retrospective study examined 94 cases of post-menopausal bleeding in which both a hysteroscopic and a histological examination were performed in the gynaecology and obstetrics department of the Hedi Chaker University of Sfax from 1 January 2004 to 28 February 2005. We examined correlations between the hysteroscopy and histology findings as well as the causes determined. RESULTS: By hysteroscopy, we observed atrophic uterine linings in 53 patients (56%), endometrial polyps in 43 patients (45%), endometrial hyperplasia in 23 patients (24%) and myomas in 24 patients (25.5%). This examination suggested malignancy in 12 patients, among 6 of whom endometrial cancer was confirmed histologically. The sensitivity and specificity of hysteroscopy were relatively poor for the diagnosis of endometrial atrophy (about 48.7% and 68.5%), acceptable for endometrial polyps (75% and 86.6%), endometrial hyperplasia (64.7% and 85.5%), and endometrial cancer (60% and 92.7%). CONCLUSION: Hysteroscopy is the most reliable technique for exploration, offering a direct view of the uterine cavity and allowing direct biopsy. Its sensitivity varies according to the indication and diagnosis and is sometimes very good. However, histology remains the reference examination for diagnosis of the cause of post-menopausal uterine bleeding.

[A new approach to studying anemia in patients with gynecological diseases and gynecological neoplasms].

The authors have used a coefficient that characterizes the functional activity of red blood cells. Evidence is provided for the significance of the coefficient, by comparing the groups of gynecological and gynecological cancer patients.

[Comparative analysis of erythrocytic indices in patients with gynecological diseases and gynecological neoplasms].

The study enrolled 177 women with gynecological cancer and 132 with gynecological disease. Hemoglobin (Hb), mean corpuscular hemoglobin (MCH), red blood cells (RBC), and erythrocyte sedimentation rate (ESR) were analyzed. The gynecological patients with anemia showed a correlation between Hb and MCH (p < 0,05), which is indicative of iron deficiency. In the gynecological cancer patients, the correlation between Hb and MCH was significant (p < 0,01), that between Hb and RBC was strong (p < 0,001), suggesting the reductions in both erythropoiesis and Hb synthesis in the erythrokaryocytes. In these patients, anemia results from chronic diseases. The gynecological cancer patients were found to have higher ESR and lower Hb, RBC, and MCH than the gynecological patients.