Mammographic breast density and IGF-1 gene polymorphisms rs1520220, rs2946834 and rs6219 in Polish women.

AIM OF THE STUDY: The aim of the study was to analyze three single nucleotide polymorphisms - rs1520220, rs2946834, rs6219 - of the IGF-1 gene in the context of breast mammographic density. MATERIAL AND METHODS: The research material included 202 samples of the peripheral blood of women with increased mammographic breast density and 238 samples of the epithelium from the oral mucosa of women without diagnosed pathological changes of the breast and with no family history of breast and/or ovarian cancer. The real-time polymerase chain reaction method was applied for analysis of polymorphisms. RESULTS: rs1520220 polymorphism was associated with increased mammographic density of the breasts. The presence of the CC genotype in the IGF-1 gene increased the risk of developing higher breast density visible in mammography by 2.43-fold. CC homozygotes (rs1520220) correlated with higher Breast Imaging-Reporting and Data System scale (3 vs. 4 and 5) (OR = 5.6; 95% CI: 1.82-16.3, p = 0.001). In the present study no relationship was detected between rs6219 and rs2946834 polymorphism and mammographic breast density. CONCLUSIONS: The results suggest that the rs1520220 polymorphism of the IGF-1 gene plays an important role in the occurrence of increased mammographic breast density.

Evaluation of sonohysterography in detecting endometrial polyps - 241 cases followed with office hysteroscopies combined with histopathological examination.

INTRODUCTION: Hysteroscopy is considered the 'gold standard' procedure in assessing uterine pathology however it is more expensive and invasive method than ultrasonography. An alternative to the diagnostic hysteroscopy is sonohysterography. AIM: To evaluate the usefulness of sonohysterography in detecting endometrial polyps in female patients diagnosed with infertility. MATERIAL AND METHODS: We compared the results of sonohysterographic examinations with hysteroscopy combined with histopathological findings. RESULTS: All the 241 sonohysterography examinations were performed successfully. No complications were observed. Forty-three hysteroscopies (17.8%) and six sonohysterography examinations (2.5%) were performed in short total intravenous anesthesia because of a low pain threshold of the patients. After hysteroscopic resection polyps were diagnosed in 74 (30.7%) patients. In 72 cases both saline infusion sonography (sonohysterography, SIS) examination and hysteroscopy confirmed the occurrence of an endometrial polyp. In 7 examinations (4.2%) the diagnosed polyp was not confirmed in sonohysterography (false-positive results). Two SIS procedures (2.7%) did not confirm the occurrence of the polyp (false-negative results). Sensitivity, specificity accuracy and error of sonohysterography in detecting endometrial polyps were 97.3%, 95.8% 96.2% and 3.7%, respectively. Positive and negative predictive values were 91.1% (PPV) and 98.7% (NPV). The agreement between SIS and hysteroscopy combined with histopathological examination was very high (K = 0.91). CONCLUSIONS: Sonohysterography is a safe and highly sensitive and specific method used in diagnostics of endometrial polyps. Its results closely correspond to those obtained in a hysteroscopic examination and histopathological analysis.

[An ongoing twin pregnancy after embryo time laps monitoring in a patient with a history of IVF failures--case report and literature review]. / Zywa ciaza blizniacza otrzymana za pomoca metody ciaglego monitorowania zarodków u pacjentki z niepowodzeniami IVF-ET--opis przypadku i przeglad pismiennictwa.

INTRODUCTION: A standard assessment of embryo morphology at given time points does not always allow to transfer the embryo with the highest implantation potential. The effect of transfer of an improper embryo results in a lack of pregnancy or a miscarriage and, as a consequence, exposes the patient to unnecessary emotional stress and necessity to perform yet another transfer of frozen embryos. We present a case of a patient with earlier IVF failures. The use of time-lapse technique in this case helped to choose two good embryos. The transfer resulted in ongoing twin pregnancy. MATERIAL AND METHODS: A 35-year-old woman with history of IVF-ET treatment failure was deemed eligible for an ICSI procedure because of the male factor. Ovarian stimulation was performed according to the agonist long protocol. Eight MII oocytes were fertilized and seven embryos were obtained. Continuous embryo monitoring was performed with the use of Primo Vision system. Forty-four hours after fertilization only 2 correctly developing embryos were identified. They were transferred on day 3. The development of the remaining 5 embryos was arrested. These embryos did not achieve the blastocyst stage on day 5-6 after fertilization. Forty days after embryo transfer a twin pregnancy, confirmed with fetal heart rate of both fetuses, was revealed on ultrasound examination. Currently the patient is at 27 weeks of ongoing twin gestation. CONCLUSIONS: The system of continuous embryo monitoring introduces new criteria for the examination of embryo development. These new parameters can be useful in clinical practice. However prospective randomized studies are necessary to provide data confirming the usefulness of time-lapse technique in IVF treatment.

Detection of intracavitary lesions in 820 infertile women: comparison of outpatient hysteroscopy with histopathological examination.

OBJECTIVES: The aim of the study was to compare the results of a diagnostic hysteroscopy with a histopathology examination (referential test) in a group of infertile women. MATERIALS AND METHODS: Eight hundred and twenty infertile patients were included in the study The subjects with intracavitary lesions underwent operative hysteroscopy to enable the removal of polyps and intracavitary myomas. Endometrial biopsy was performed in all patients with no pathologies in hysteroscopy. The removed tissue underwent histopathological examination. RESULTS: The mean age was 32.9 +/- 4.1. A total of 648 (79%) patients were diagnosed with primary and 172 (21%) with secondary infertility; 542 (66.1%) hysteroscopies were performed with no anesthesia and 278 (33.9%) hysteroscopies were performed in short total intravenous anesthesia. Sensitivity and specificity accuracy, error positive predictive value (PPV) and negative predictive value (NPV) of hysteroscopy in detecting endometrial lesions were 99.6%, 96.6%, 97.4%, 2.6%, 92.2% (PPV) and 99.8% (NPV), respectively. The agreement between hysteroscopy and pathology report was very high (kappa K = 0.94). In case of normal uterine cavity 562 of the 563 endometrial samples showed evidence of normal endometrium. In all 32 cases of resected submucosal myomas histopathology confirmed the hysteroscopic findings (sensitivity 100%, specificity 100%, accuracy 100%, error 0%, kappa K = 1.0). Both, hysteroscopy and histopathology confirmed the presence of endometrial polyps in 199 cases. The diagnosis of a polyp was not confirmed in histopathological findings (false-positive results) in 20 hysteroscopies. No endometrial polyps were missed during hysteroscopy Sensitivity specificity accuracy error positive and negative predictive values in detecting endometrial polyps were 100%, 96.8%, 97.6%, 2.4%, 90.9% (PPV) and 100% (NPV), respectively. The Kappa coefficient agreement between hysteroscopy and histopathology for endometrial polyps was 0.91. CONCLUSIONS: Hysteroscopy is a method of high sensitivity and specificity in detecting pathologies, but in case of a pathology it cannot replace histological examination. Our result show that a routine endometrial biopsy performed in infertile patients with no pathology in hysteroscopy should not be recommended.

IL-18 and IL-18 binding protein concentration in ovarian follicular fluid of women with "tubal factor" subjected to in vitro fertilization.

INTRODUCTION: Composition of follicular fluid is also regarded to be linked to quality of oocytes, fertilization and quality of the embryo. The aim of this study was to investigate the concentration of IL-18 and IL18BP in follicular fluid (FF) in a homogeneous group of women with sterility caused by "tubal factor" subjected to in vitro fertilization (IVF) and the relation between concentrate of this cytokine and IVF outcome. MATERIALS/METHODS: The study group consisted of 83 non-smoking women aged 30.9 ± 3.2 (23.0-43.0) with confirmed (hysterosalpingography and/or laparoscopy) bilateral complete tubal impermeability. Follicular fluid levels of IL-18 and IL18BP were evaluated in 83 patients undergoing in vitro fertilization (IVF). Ovarian hormonal stimulation was conducted according to a GnRH antagonist protocol. The measurement of IL-18 and IL18BP in follicular fluid was done using the ELISA method. RESULTS: The mean follicular levels of IL-18 and IL18BP were 468.5 ± 357.4 pg/ml and 8611.3 ± 534 pg/ml. The biochemical pregnancy rate was 39.7% (33/83); 22 women became clinically pregnant (26.5%). The implantation rate was 26.7% (36/135). No significant correlation was found between follicular concentrations of IL-18 and age of the patients (r = 0.13 p>0.05), number of metaphase II oocytes collected (r = -0.11 p>0.05), number of 3-day embryos (r = -0.157 p>0.05), biochemical pregnancies (r = 0.03 p>0.05), or clinical pregnancies (r = -0.06 p>0.05). Also there was no significant correlation between IL18BP and age of the patients (r = 0.21 p>0.05), number of metaphase II oocytes collected (r = 0.08 p>0.05), number of 3-day embryos (r = -0.19 p>0.05), biochemical pregnancies (r = 0.11 p>0.05) and clinical pregnancies (r = -0.34 p>0.05). CONCLUSION: IL-18 and IL18BP are detectable in follicular fluid but do not determine IVF outcome in women with "tubal factor". IL-18 and IL18BP are not promising prognostic markers for IVF success in this subgroup of patients.

Coagulation and fibrynolitic parameters in women and the effects of hormone therapy; comparison of transdermal and oral administration.

It is established that hormone therapy (HT) is related with significant increased prothrombotic risk factor. The aim of our study was to assess the effects of oral hormone therapy (o-HT) and transdermal hormone therapy (t-HT) on hemostasis parameters: fibrinogen (Fg) concentration, the maximum velocity of polymerization of clot formation, fibrin half-time lysis, plasma level of thrombin inhibitor of fibrinolysis (TAFI) and activity of generated thrombin and plasmin amidolytic activity. We observed that values of initial velocity of polymerization in o-HT group were increased (94.64 mOD/min vs. 131.50 mOD/min, p < 0.001) compared to control group. Fibrin lysis half-time increased in both groups with HT (controls - 18.26 min vs. 32.43 min (o-HT); 23.34 min transdermal hormone therapy (t-HT) p < 0.001) compared to controls. The activity of thrombin was statistically higher in plasma of women after o-HT (72.6 ± 8.5 mOD/min) than in patients with t-HT (53.7 ± 10.1 mOD/min) and controls (51.2 ± 10 mOD/min. Plasmin activity was the highest in controls (84.5 ± 10.2 mOD/min). The highest level of TAFI we observed in patients after oral hormones (80.38 ± 8.23%); women on transdermal HT had 61.58 ± 9.81% and the lowest concentration of TAFI we noted in controls 44.70 ± 10.16). The results of our study show that HT may partly explain the increase in venous thrombosis (VTE) and cardiovascular events reported after the use of it, especially the oral form of treatment.

Oxidative stress markers in follicular fluid of women undergoing in vitro fertilization and embryo transfer.

The aim of the study was to evaluate the levels of lipid and protein peroxidation markers, in the follicular fluids (FF) of 82 patients undergoing in vitro fertilization (IVF). This included, thiobarbituric acid-reactive substances (TBARS), protein carbonyl, and thiol groups. The oxidative stress markers were compared between the pregnancy positive and pregnancy negative patient groups. The two patient groups were compared in terms of their age, body mass index (BMI), cause of infertility, and the plasma hormone levels (AMH, E(2), peak E(2)). Protein carbonyl and thiol groups were estimated using an ELISA assay and with Ellman's reagent (5, 5'-dithiobis-2-nitrobenzoic acid, DTNB), respectively. The mean FF TBARS level of 29 pregnant women was 0.954 ± 0.420 µmol/l, whereas it was twice as high (1.961 ± 0.796 µmol/l) in a group of 53 non-pregnant patients (p < 0.0001). In non-pregnant patients, we observed 2-fold elevated levels of protein carbonyl groups when compared to pregnant women (2.969 ± 0.723 vs. 1.523 ± 0.254; p < 0.0001). The mean age of women and BMI were significantly higher in the pregnancy negative vs. pregnancy positive group. There were no significant differences in protein thiols and in the levels of the hormones tested between patient groups. Our results demonstrate that elevated FF lipid and protein peroxidation level may have a negative impact on IVF outcome. The findings support the idea that increased level of oxidative stress markers in follicular fluid may play an important role in fertility.

Single nucleotide polymorphism (SNP) Thr241Met in the XRCC3 gene and breast cancer risk in Polish women.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual's risk of cancer. The XRCC3 protein plays a critical role in Homologous Recombination Repair (HRR) accounting for repair of DNA double-strand breaks (DSB). AIM: The aim of the present study was to evaluate associations between the risk of breast cancer and Thr241Met polymorphism in the XRCC3 gene. MATERIAL AND METHODS: Single nucleotide polymorphism was genotyped by the PCR-RFLP (restriction fragment-length polymorphism) method in 760 women with sporadic breast cancer and in 760 control samples. The present study confirmed a relationship between XRCC3 Thr241Met polymorphism and breast cancer progression, assessed by the degree of lymph node metastases and histological stages. CONCLUSION: Our findings suggest that the analysis of XRCC3 polymorphism, may contribute to better understanding of the mechanisms of breast cancer by evaluating possible interactions between these genotypes and well-established risk factors for breast cancer.

Oxidative stress measured by carbonyl groups level in postmenopausal women after oral and transdermal hormone therapy.

AIM: Menopause is associated with an increased risk of cardiovascular disorders, which are accompanied by oxidative stress. Our study was undertaken to determine whether oxidative stress in menopausal women could be reduced after six months of oral or transdermal hormonal therapy. MATERIAL AND METHODS: Carbonyl groups of proteins in blood plasma were estimated by sensitive ELISA method with anti-DNP antibodies. In this method, protein samples diluted in phosphate-buffered saline were adsorbed to wells of an ELISA plate and then reacted with dinitrophenylhydrazine (DNPH). RESULTS: Plasma protein carbonyl levels of postmenopausal women treated with o-HT and t-HT for six months (o-HT: 1.785 ± 0.31 nmol/mg; t-HT: 1.838 ± 0.33 nmol/mg) were lower when compared with the control group (2.232 ± 0.28 nmol/mg). There was no statistically significant difference in carbonyl levels between women after oral and transdermal HT (P = 0.149). CONCLUSION: Hormonal therapy reduces the level of carbonyl protein, a marker of oxidative stress, suggesting potential protective effect.

Single nucleotide polymorphisms of RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met homologous recombination repair genes and the risk of sporadic endometrial cancer in Polish women.

BACKGROUND: The genes RAD51, XRCC2 and XRCC3 encode proteins that are important for the repair of double-strand DNA breaks by homologous recombination. Therefore, genetic variability in these genes may contribute to the occurrence and progression of endometrial cancer. METHODS: The subject of investigation in the reported study was the distribution of genotypes and the prevalence of alleles of the RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met polymorphism in 230 cases of sporadic endometrial cancer; the polymorphisms were determined by polymerase chain reaction-restriction fragment-length polymorphism methods. RESULTS: The obtained results demonstrated a significant positive association between the RAD51 C/C genotype and endometrial carcinoma, with an adjusted odds ratio (OR) of 3.75 (P < 0.0001). The homozygous C/C genotype was found in 72% of endometrial cancer cases and in 19% of the used controls. The variant 135C allele of RAD51 increased the cancer risk (OR = 1.64 [1.28-2.10]P < 0.0001). There were no significant differences between the distribution of G135C, Arg188His and Thr241Met genotypes in the subgroups assigned to histological grades. CONCLUSIONS: The obtained results indicate that the polymorphism of RAD51, but not of either XRCC2 or XRCC3 genes, may be positively associated with the incidence of endometrial carcinoma in the population of Polish women. Further studies, including those on a larger group of patients, are required to further clarify this point.

Single nucleotide polymorphisms in the homologous recombination repair genes and breast cancer risk in Polish women.

Genetic polymorphisms in homologous recombination repair genes that can lead to protein haploinsufficiency are generally associated with increased cancer risk. The aim of the present study was to evaluate associations between the risk of breast cancer and single nucleotide polymorphisms in the genes, encoding three key proteins of the homologous recombination repair: RAD51 (the human homologue of the E. coli RecA protein), X-ray repair cross-complementing group (XRCC) 2 and XRCC3. The polymorphisms studied were G135C of the RAD51 gene (c. -98 G>C; rs1801320), Arg188His of the XRCC2 gene (c. 563 G>A; rs3218536), and Thr241Met of the XRCC3 gene (c. 722 C>T; rs861539). Each polymorphism was genotyped by the PCR-RFLP (restriction fragment-length polymorphism) method in 700 Polish female patients with sporadic breast cancer and in 708 cancer-free women, who served as controls. In the present study, we showed the association between RAD51 G135C polymorphism and the incidence of breast cancer (p < 0.0001), but found no significant association with XRCC2 Arg188His or XRCC3 Thr241Met polymorphism. Instead, significant association was identified between XRCC2 Arg188His or XRCC3 Thr241Met polymorphism and breast cancer progression, assessed by the histological grading. However, each of these three polymorphisms was not associated with the tumor size or the lymph node metastases. This study provides evidence that links single nucleotide polymorphisms of RAD51 and XRCC2/3 genes with the risk of breast cancer in Polish women. In conclusion, RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be regarded as predictive factors of sporadic breast cancer in female population.

Changes in hemostatic parameters after oral and transdermal hormone therapy in postmenopausal women.

Hormone therapy (HT) can be prothrombotic risk factor. We compared the effects of oral HT (o-HT) and transdermal HT (t-HT) on the kinetic of clot formation and fibrinolysis in postmenopausal women after 6 months HT using a multiparameter test. We observed that after HT, the level of fibrinogen was higher than in controls (Fg 3.12 g/l vs. 4.24 g/l (o-HT); 3,7 g/l (t-HT); p < 0.001) and values of velocity of polymerization in o-HT group were increased (95.84 mOD/min vs. 146.50 mOD/min, p < 0.001) compared to controls. Maximum absorbance of formed clots was higher in o-HT group (0.279 vs. 0.312, p < 0.001) than in controls, but in t-HT group was lowest (0.268). Fibrin lysis half-time increased in both HT groups (controls 17.16 min vs. 31.43 min (o-HT); 23.34 min (t-HT) p < 0.001) compared to values in controls. The results of our study show that o-HT caused the changes in clot formation and fibrinolysis than t-HT in postmenopausal women. The increased level of fibrinogen and its accelerated kinetics of polymerization as well as a lower rate of clot lysis may partly explain the increase in venous thrombosis and cardiovascular events reported after the use of HT, especially the oral form of that.

Changes in hemostatic parameters after oral hormone therapy in postmenopausal women.

OBJECTIVE: Oral hormone therapy (HT) and menopausal age are both prothrombotic risk factors. The aim of our study was to compare the hemostatic parameters in plasma of postmenopausal women after 6 months of oral HT with parameters of control (without treatment) postmenopausal women. METHODS: Twenty-seven postmenopausal women were treated with 17ß-estradiol (1 mg) and dydrogesterone (5 mg) daily for 6 months. The control group (27 women) did not receive any HT. Hemostatic factors, such as fibrinogen (FG) concentration, activated partial thromboplastin time (APTT), platelet (PLT) count, maximum velocity of clot formation, and fibrin lysis half-time were estimated. RESULTS: The hemostatic parameters in both groups differ significantly. After 6 months oral HT, APTT and the level of FG were higher than in the control group (APTT 30.08 seconds vs. 28.18 seconds, p = 0.02; FG 4.14 g/L vs. 3.03 g/L, p < 0.001). However, the higher values of maximal velocity of FG polymerization (153.53 mOD/min vs. 92.87 mOD/min, p < 0.001), maximum absorbance values (0.306 vs. 0.275, p < 0.001), and fibrin lysis half-time (32.33 minutes vs. 18.11 minutes, p < 0.001) compared with values in the control group also were observed. There was no statistically significant difference in PLT counts between control and women treated with oral HT. CONCLUSIONS: Six months of oral combined HT (17ß-estradiol and dydrogesterone) caused increased initial velocity of clot formation and inhibition of fibrinolysis. The increased level of FG and its higher polymerization may help explain the increase in venous thrombosis and cardiovascular events reported after the use of oral HT.

The CYP17 and CYP19 gene single nucleotide polymorphism in women with sporadic breast cancer.

The cytochrome P450 family (CYPs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. We hypothesise that polymorphisms of CYP17 and CYP19 gene can predict higher incidence of breast cancer. In the present work the distribution of genotypes and frequency of alleles of the T/C polymorphism in promoter region of CYP17 and Trp/Arg polymorphism in codon 39 of CYP19 gene in breast cancer women were investigated. The genetic polymorphisms analysis was performed by amplifying DNA by PCR-RFLP methods in 100 sporadic breast cancer cases. The distribution of the genotypes of the T/C polymorphism of CYP17 in patients differed significantly (p < 0.05) from those predicted by the Hardy-Weinberg equilibrium. There were significant differences in the frequencies of alleles between the breast cancer subjects and controls (p < 0.05). However, the distribution of the genotypes of the Trp/Arg polymorphism of CYP19 in both control and patients did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. The results support the hypothesis that the T/C polymorphism of CYP17 gene may be associated with the incidence of breast cancer in women from Lodz region of Poland.

Ser326Cys polymorphism in DNA repair genes hOGG1 in breast cancer women.

Reduced DNA repair capacity can render a high risk of developing many types of cancer; including breast cancer. Polymorphisms in DNA repair genes may contribute the genetic instability and carcinogenesis. In the present work the distribution of genotypes and frequency of alleles of the Ser326Cys polymorphism of hOGG1 gene in breast cancer women were analysed. Blood samples were obtained from 100 women with breast cancer and control (n = 106). The polymorphism was determined by PCR-RFLP methods. No association between Ser326Cys polymorphism of hOGG1 and breast cancer risk was observed. The distribution of the genotypes of the Ser326Cys polymorphism in both control and patients did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p > 0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the Ser326Cys polymorphism of hOGG1 gene may not be linked with appearance and development of breast cancer in polish women.

[The impact of hormone replacement therapy applied in women with varicose vein on changes in coagulation and fibrinolysis]. / Wplyw hormonalnej terapii zastepczej na wybrane parametry ukladu krzepniecia i fibrynolizy u kobiet z zylakami konczyn dolnych.

UNLABELLED: In fifty two postmenopausal women (study group: n = 20 with varicose vein; controls: n = 32) with climacteric symptoms some changes in fibrinolytic and coagulative parameters were measured during six months of HRT consisted of transdermal oestradiol (17 beta-E2) and oral medroxyprogesterone acetate (MPA). Additionally, sonographic examinations of the venous system of pelvis minor and low extremities were performed three times in every women--at baseline, in the 3rd and the 6th month of the trial. In the 3rd month the varicose vein group exhibited lowered INR and t-PA, but the in 6th month increased D-dimer as compared to the controls. No sonographic signs of venous thromboembolism were detected. CONCLUSIONS: 1) Postmenopausal varicose vein women taking combined HRT (17 beta-E2 plus MPA) are on slightly increased additional risk of venous thromboembolism, 2) in monitoring of these patients sonographic evaluation of the venous system of low extremities and pelvis minor and well as D-dimer in blood serum should be done.

[Evaluation of the effect of obesity on selected haemostatic and fibrinolytic parameters in peri- and postmenopausal women]. / Ocena wplywu otylosci na wybrane parametry ukladu krzepniecia i fibrynolizy u kobiet w okresie okolo-i pomenopauzalnym.

Localization of adipose tissue influence on obesity-dependent diseases. In obese people many abnormalities are observed connected with coagulation factors and fibrinolysis. We studied 47 peri- and postmenopausal female patients, who were operated on for benign changes within the pelvis minor. The patients were divided according to BMI (group I--BMI < 25 kg/m2, group II--BMI > 29 kg/m2). In obese women lower SHBG concentration, higher insulin and glucose fasting blood levels, higher LDL, higher total fatty tissue content, higher fibrinogen level and elevated PAI-1 activity were found. A positive correlation between area under insulin curve and PAI-1 activity and a negative correlation between fasting insulin levels and tPA were also observed. Based on the studies performed it can be said that: 1. Fatty tissue content in postmenopausal women exerts an influence on PAI-1 activity. 2. Obesity influences coagulation and fibrinolysis system in peri- and postmenopausal women. 3. Carbohydrate metabolism disturbances have influence on PAI-1 activity in peri- and postmenopausal women.