Ali Rıza Odabaşı

Effects of postmenopausal hormone replacement therapy on body fat composition

Aim. To evaluate the effects of different types, regimens and administration routes of hormone replacement therapy (HRT) on body fat composition indices in postmenopausal women at increased risk of anthropometry-related cardiovascular disease (CVD). Methods. Fifty-nine postmenopausal women (aged 41–57 years, mean ± standard deviation: 49.9 ± 3.8 years) with body mass index (BMI) ≥25 kg/m2 participated in this 6-month, prospective, randomized single-blind study. Subjects were assigned into three groups and received transdermal estradiol (E2)/norethisterone acetate (NETA) (50 μg E2 daily for 14 days followed by 50 μg E2/0.25 μg NETA daily for 14 days; transdermal group, n = 19), transdermal continuous E2/oral medroxyprogesterone acetate (MPA) (50 μg E2/5 mg MPA daily; transdermal/oral group, n = 19) or oral continuous E2/NETA (1 mg E2/0.5 mg NETA daily; oral group, n = 21). Anthropometric indices (body weight, height, and hip and waist circumferences) were measured, and BMI and waist-to-hip ratio (WHR) were calculated, before and after treatment. Also, the thickness of subcutaneous abdominal fat was measured by ultrasound. Depending on waist circumference (WC), the subjects were divided into two risk groups: increased-risk group with WC <88 cm (n = 32) and high-risk group with WC ≥88 cm (n = 27). Also, the effects of HRT were evaluated separately in subjects with median subcutaneous fat of <33 mm (n = 29) and those with median subcutaneous fat of ≥33 mm (n = 30). Results. Overall, all three types of HRT caused a significant decrease in both WC and subcutaneous fat (p < 0.001), and also in WHR (p < 0.05). There was no significant difference in baseline (p > 0.05) and final values (p > 0.05) between HRT groups. In each group, all types of HRT significantly decreased WC and subcutaneous fat (transdermal group: p < 0.001 and p < 0.05; transdermal/oral group: p < 0.001 and p < 0.01; oral group: p < 0.001 and p < 0.001, respectively), while body weight, BMI and WHR changed only insignificantly (p > 0.05). In the increased-risk group, body weight increased significantly (p < 0.05) while WC and subcutaneous fat decreased significantly (p < 0.001 and p < 0.001). As for the high-risk group, there was a significant decrease in WC and subcutaneous fat (p < 0.001, p < 0.001) while the remaining parameters did not change significantly. However, BMI showed a tendency to increase in the increased-risk group, while there was a decrease in all measurements in the high-risk group. Regardless of the drugs used and baseline subcutaneous fat, WC and subcutaneous fat decreased significantly at the end of the treatment (subcutaneous fat <33 mm: p < 0.001 and p < 0.01; subcutaneous fat ≥33 mm: p < 0.001 and p < 0.001, respectively). Conclusions. The three different types of HRT have comparable effects on central fat tissue in women at increased risk of anthropometry-related CVD. Indeed, the three combinations of HRT reduced fat tissue in the central part of the body. However, the overall effect of HRT was more marked in women with WC ≥88 cm and subcutaneous fat ≥33 cm. Whether HRT increases body weight depends on the body composition indices of individuals before treatment.

Effects of oral continuous 17β-estradiol plus norethisterone acetate replacement therapy on abdominal subcutaneous fat, serum leptin levels and body composition

Aim. To evaluate the effects of oral continuous 17β-estradiol plus norethisterone acetate (E2/NETA) replacement therapy on abdominal subcutaneous fat, serum leptin level (SLL) and body composition in postmenopausal women. Materials and methods. A 6-month, prospective, randomized, double-blind and placebo-controlled study was conducted. Forty-three healthy naturally postmenopausal women aged 43–65 years were randomly assigned to receive E2/NETA (2 mg E2 plus 1 mg NETA, n = 22) or placebo (n = 21). Fasting SLL by enzyme-linked immunosorbent assay, subcutaneous abdominal fat thickness (STh) by ultrasound and the anthropometric indices of body weight (BW), body mass index (BMI), waist and hip circumference (WC, HC) and waist-to-hip ratio (WHR) were recorded at the beginning and the end of the study. Results. After 6 months of therapy, BW and SLL increased in the placebo group (p = 0.043 and 0.033, respectively). WC, HC and STh decreased significantly in the E2/NETA group (p = 0.002, 0.006 and 0.000, respectively) and they were also significantly lower in women receiving E2/NETA than in women taking placebo (p = 0.000, 0.034 and 0.000, respectively). At baseline, SLL and STh were positively correlated with all anthropometric indices except WHR. Conclusion. Oral continuous combined regimen of E2/NETA significantly reduced central fat accumulation as assessed by WC and STh, and attenuated the increase in SLL. The observed changes in SLL were highly and positively related to changes in STh. The oral continuous combined E2/NETA regimen appears to have protective effects on cardiovascular function and probably on metabolic diseases by its slimming effect upon WC in postmenopausal women.

Circulating galanin and IL-6 concentrations in gestational diabetes mellitus

Abstract Objective: The aim of this study is to compare galanin and IL-6 levels in pregnant women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Also association of insulin resistance markers, galanin and IL-6 was investigated. Materials and Methods: The study registered 30 pregnant women with GDM and 30 pregnant women with NGT. Fasting venous blood samples were collected from all patients. Galanin and IL-6 levels were measured by an enzyme-linked immunosorbent assay. Results: Galanin and IL-6 levels were found higher in pregnant women with GDM (p < 0.001). A significant positive correlation was determined between galanin concentrations and glucose (r = 0.240, p = 0.065), insulin (r = 0.681, p < 0.001), HbA1c (r = −0.644, p < 0.001), IL-6 (r = 0.783, p < 0.05) and oral glucose challenge test results (r = 0.745, p < 0.001) in pregnant women included in study, whereas no significant association was determined between galanin and gestational age (r = 0.058, p = 0.662), body mass index (r = −0.019, p = 0.886). Conclusion: Galanin and IL-6 were found to be significantly associated with insulin resistance markers in GDM, thus may play important roles in regulation of glucose hemostasis.

VEGF, PIGF and HIF-1α in placentas of early- and late-onset pre-eclamptic patients

Abstract Purpose: The aim of this study was to compare the VEGF, PIGF, and HIF-1α levels in the placentas of early- and late-onset pre-eclamptic patients, which are thought to be important in pathophysiology of pre-eclampsia. Material and method: Pre-eclamptic early-onset (n = 22) and late-onset (n = 24) pregnant women and a control group of healthy pregnant women (n = 22) were recruited for this case–control study. A semi-quantitative immunohistochemical analysis of VEGF, PIGF and HIF-1α was performed in cross-sections of the placentas of the subjects, after which results were compared. Results: Levels of VEGF and PIGF in the placentas of pre-eclamptic patients were found to be lower than the levels in the placentas of healthy pregnant women (p < 0.001 and p = 0.025, respectively), whereas the levels of HIF-1α were found significantly higher (p < 0.001). No difference was observed in terms of VEGF, PIGF and HIF-1α in a comparison of the early- and late-onset pre-eclampsia groups (p > 0.05). Conclusion: The results of the study indicated that there is no relationship between the time of onset of pre-eclampsia and the placental changes that occur in these factors.

Comparison of angiogenic and anti-angiogenic factors in maternal and umbilical cord blood in early- and late-onset pre-eclampsia

Purpose: The aim of this study was to compare maternal and umbilical cord serum levels of the angiogenic and anti-angiogenic factors in early- and late-onset pre-eclamptic pregnancies as well as in normal pregnancies, which might have significant importance in the etiology of pre-eclampsia. Materials and Methods: This prospective case-control study was carried out with pre-eclamptic (early-onset, ≤ 34 weeks and late-onset, >34 weeks) and normal pregnant women. VEGF, PIGF, sFlt-1 and sEng levels in maternal and umbilical cord serum were measured before delivery and the findings were compared. Results: The study was conducted with 15 early- and 15 late-onset pre-eclampsia patients, and 17 patients with normal pregnancies. It was found that sEng levels were higher in the umbilical cord serum in the early-onset and in the maternal serum in the late-onset pre-eclampsia group than the control group (p < 0.05). No significant difference in any factor was observed between the early- and late-onset pre-eclampsia groups. Conclusion: In this study, the results showed that angiogenic and anti-angiogenic factor levels in maternal serum and umbilical cord serum may not be related to the time of onset of pre-eclampsia.

Effects of tibolone on abdominal subcutaneous fat, serum leptin levels, and anthropometric indices: a 6-month, prospective, randomized, placebo-controlled, double-blind study.

This study was undertaken to evaluate the effects of tibolone on abdominal subcutaneous fat, serum leptin levels (SLLs), and anthropometric indices, and to investigate potential relationships between SLLs, subcutaneous abdominal fat thickness, and anthropometric indices in postmenopausal women. In a 6-mo, prospective, randomized, double-blind, placebo-controlled study, 40 healthy postmenopausal women aged 42 to 67 y (mean: 50±4.7 y) were randomly assigned to 1 of 2 groups; during a 6-mo treatment period, the first group received tibolone (Livial® tablet; Organon, The Netherlands; 2.5 mg/d; n=19) and the other group was given placebo (n=21). Fasting SLLs determined by enzyme-linked immunosorbent assay, subcutaneous abdominal fat thickness assessed by ultrasound, and anthropometric indices of body weight, body mass index, waist and hip circumference, and waist-to-hip ratio (WHR) were recorded at the beginning and the end of the study. Statistical analyses were performed with Mann-Whitney, Wilcoxon, and Spearman tests.P values < .05 were considered significant. No significant differences between the 2 groups were reported in terms of all baseline characteristics. After 6 mo, body weight (+0.77±0.43 kg) and SLLs (+14.7±6.4 ng/mL) increased in the placebo control group, whereas waist circumference (-2.6±3.0 cm), hip circumference (-3.6±3.5 cm), and subcutaneous abdominal fat thickness (-4.3±4.8 cm) decreased significantly in the tibolone group (P < .05). At the end of the study, group comparisons revealed significant differences in waist and hip circumference and subcutaneous abdominal fat thickness (P < .05). At baseline, SLLs were correlated with subcutaneous abdominal fat thickness and all anthropometric indices except WHR (P < .05). Subcutaneous abdominal fat thickness was also highly correlated with all indices except WHR (P < .0001). Tibolone was found to decrease waist and hip circumference, as well as subcutaneous abdominal fat thickness. Also, tibolone appeared to attenuate weight gain and leptin increase. SLLs and subcutaneous abdominal fat thickness were positively correlated with all anthropometric indices except WHR.

Effects of Sevoflurane on QT Dispersion and Heart Rate Variability

The purpose of this study was to use estimates of corrected QT dispersion (QTcd) and heart rate variability (HRV) to assess the effects of sevoflurane, an inhalation agent used frequently in clinical practice, on autonomic cardiac function. This study was conducted prospectively and in a blind manner on 20 women between 38 and 51 y of age who were classified as American Society of Anesthesiologists stage I–II and whose treatment required total abdominal hysterectomy. Electrocardiograms were recorded by 12-lead Holter monitor for 5 min before sevoflurane induction and again for 5 min at 10 min after tracheal intubation. Data on the first recording were considered as baseline; those on the second recording were viewed as final data. The study was terminated at this point, and surgery was allowed to proceed. QTcd and HRV values were assessed by a cardiologist, who was blinded to all data. All parameters were expressed as a mean value ± standard deviation. Wilcoxon’s test was used to compare baseline and final data. Statistical significance was considered asP< .05. No significant changes were observed between baseline and final QTcd values and between low and high-frequency components (LF and HF) of HRV; nor were changes seen in the LF/HF ratio. With the patient under sevoflurane/nitrous oxide anesthesia, no significant changes were detected in QTcd, LF, and HF values, and in the LF/HF ratio, whereas a significant increase (P=.001) was seen in standard deviation of the R-R interval, which was used as a measure of cardiac autonomic tone.

Comparison of interleukin-6 levels in maternal and umbilical cord blood in early- and late-onset preeclampsia.

Purpose: Increased inflammatory response and cytokines are claimed to play a significant role in the etiology of preeclampsia. Interleukin-6 (IL-6) is a proinflammatory cytokine. Limited number of studies evaluating IL-6 levels in preeclamptic patients have produced conflicting results. Therefore, the present study sought to compare maternal and umbilical cord serum levels of IL-6 in early- and late-onset preeclamptic pregnancies as well as in normal pregnancies. Materials and methods: A total of 69 participants were enrolled in the study. The control group consisted of 24 participants with normal pregnancies. Preeclampsia group consisted of 45 participants. The preeclampsia group was further classified into the subgroups of early- and late-onset preeclampsia. Late-onset preeclampsia group consisted of 24 women whereas early-onset preeclampsia group consisted of 21 women. Serum and umbilical cord samples of IL-6 were compared. Results: There was no significant difference between maternal and umbilical cord serum IL-6 concentrations between the preeclampsia and control group. No significant difference was observed in maternal and umbilical cord serum IL-6 levels between early- and late-onset preeclampsia groups. Conclusion: Our results do not support an increase in IL-6 levels in patients with early- and late-onset preeclampsia. The clinical relevance of our findings needs to be further investigated.

Effects of early initiated oestrogen replacement therapy on plasma homocysteine levels in women in surgically induced menopause.

Objective. The aim of this study was to investigate and to compare the effects on serum homocysteine levels of early initiated oral and transdermal oestrogen replacement therapies (ERTs) given to women without a uterus who had undergone surgically induced menopause. Homocysteine levels are considered one of the predictors of cardiovascular disease risk. Methods. This study included 45 women with surgical menopause. Of 45 women, 15 received oral ERT, (oestradiol hemihydrate 2 mg/day, Estrofem®), 15 received transdermal ERT (oestradiol hemihydrate 0.1% gel 1.5 mg/day, Estreva®) and 15 received no hormone therapy. Blood samples were collected from all women to measure homocysteine levels at the mean time of 15 weeks after surgical menopause. Obtained results of the groups were compared. Results. There were no significant differences in age, height, weight, body mass index (BMI), waist circumference and time elapsing since menopause between the three groups. The duration of ERT was not significantly different between the therapy groups. There was no significant difference in homocysteine levels between the groups (p > 0.05). No significant correlation was found between weight, BMI and homocysteine levels (p > 0.05). Conclusion. Considering that homocysteine is a predictor of risk for cardiovascular disease, the results of this study showed that early initiation of ERT in healthy surgically induced menopausal women neither protects nor deteriorates cardiovascular disease.

Evaluation of smoking as a risk factor for activated protein C resistance during pregnancy.

Objective: The effect of smoking on the activated protein C (APC) ratio in normal gestation was systematically investigated. The frequency of acquired APC resistance (APCR) in the smoking and non-smoking subjects with normal follow-up of pregnancy and the outcome observed in these two groups were documented. Study Design: A total of 180 normal pregnant women (non-smokers 138, smokers 42) in different trimesters of gestation admitted to the hospital were enrolled into a cross-sectional study. APC ratio, factor V, factor VIII, protein S and protein C were quantitated. Factor V Leiden mutation analyses were performed by real-time PCR. Results: This cross-sectional study tries to detail the effect of smoking on APCR together with the changes in some components of the protein C/protein S system which may contribute to alterations in the APC ratio in normal gestation. A decreased APC ratio observed in pregnancy was statistically significant in the smokers (p = 0.03). When the trimesters were taken into consideration, APC ratios were significantly lower in the third trimester in the smokers compared with the non-smokers in the same trimesters (p = 0.001). The difference in the APC ratio between the groups in early pregnancy was not significant. Conclusion: These studies have demonstrated that the modified test abolishes the pregnancy-related effect on the APCRs in normal pregnant non-smoking women presumably by normalization of coagulation factors (except factor V). Our result for the non-smoking group is consistent with data provided in previous studies. However, we noted a very significant decrease in the APC ratio in smoking pregnant women in the third trimester, most likely secondary to decreased factor V levels.