Ireneusz Połać

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.

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 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.

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 17β-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 (17β-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.

Hemostatic variables, carbohydrate metabolism and lipid profile in women with low body mass index.

The aim of this study was to evaluate hemostatic variables in women according to different body mass index (BMI) values ,and then correlate them with some metabolic parameters - fasting insulin and glucose, total cholesterol ,high-density lipoprotein (HDL)-cholesterol ,low-density lipoprotein (LDL)-cholesterol and triglycerides. Eighty-four female patients aged 18-39 years were recruited ,and agreed to participate in the study. The study group was divided into three subgroups according to BMI: low BMI (BMI < 18.5 kg/m2; n = 43) ,normal-weight (control) (BMI 18.5-24.99 kg/m2; n = 21) and overweight/obese (BMI > 25 kg/m2; n = 20). BMI was calculated ,and the following measurements were taken: International Normalized Ratio ,antithrombin III ,tissue plasminogen activator (t-PA) activity ,t-PA-antigen, plasma fibrinogen level ,factor VII ,Plasminogen activator inhibitor (PAI)-1 activity and antigen and metabolic parameters: fasting insulin and glucose ,total cholesterol ,HDL-cholesterol ,LDL-cholesterol and triglycerides. The results were statistically analyzed. In the low BMI group ,a negative correlation between fasting insulin and PAI-1 activity ,and a positive correlation between fasting glucose and PAI-1 antigen were observed. Also ,a strong negative correlation between PAI-1 activity and insulin/glucose index was found. Plasma insulin levels were significantly lower in the low-BMI women than in the overweight/obese group (p < 0.001) and with no difference compared to the control group. We did not find any difference in fasting glucose level between all groups. HDL-cholesterol showed the highest levels in the normal BMI group and was significantly higher than in the low BMI and obese groups (p < 0.05 and p < 0.01 ,respectively). PAI-1 activity in the low BMI women revealed increased activity in comparison to control and overweight/obese women (p < 0.001 and p < 0.05 ,respectively). Lower antigen levels were also shown as compared to both these groups (p < 0.001 and p < 0.001 ,respectively). Similar results were obtained with t-PA antigen levels (p < 0.001 and p < 0.001 ,respectively). There were no differences in activity of t-PA in all groups. Obese women showed significantly higher fibrinogen levels than other BMI groups (p < 0.001 and p < 0.001 respectively). Analysis of hemostatic variables in women with a low BMI testify to the impaired fibrinolysis in this group ,also showing a strong correlation with carbohydrate metabolism.

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.