Bülent Özçelik

Predictive value of tumor necrosis factor alpha (TNF-α) in preeclampsia

Abstract Objective : To assess the measurement of plasma tumor necrosis factor alpha (TNF-α) as a predictive test for the development of preeclampsia. Study Design : One-hundred and twenty pregnant women were included in this prospective longitudinal study. Maternal plasma TNF-α levels were measured in the first, second and third trimesters by immunosorbent assay (ELISA). Preeclamptic patients were determined prospectively. Preeclamptic and normotensive patients were compared to assess the predictive value of TNF-α in preeclampsia. Results : Ninety patients completed the study. Preeclampsia developed in 10 out of 90 patients (11.1%). Plasma TNF-α levels were higher in preeclamptic patients than normotensive women in the third trimester of pregnancy ( P P >0.05). With the use of the receiver operating characteristics (ROC) 10.13pg/ml was found to be a cut-off value predictive for the development of preeclampsia in the third trimester, but cut-off values in the first and second trimesters could not be found. The specificity, sensitivity, positive and negative predictive values were 90, 78, 33 and 98%, respectively. Conclusion : This study shows that plasma TNF-α levels are not useful as a specific marker for prediction of preeclampsia in the first and second trimesters. But determination of TNF-α may be useful for the prediction in the early third trimester.

Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism.

Combined oral contraceptives (COCs) are considered the first-line treatment for women with hirsutism. They diminish androgen release from the ovary and decrease plasma free testosterone levels by increasing sex hormone-binding globulin (SHBG) concentrations. COCs containing cyproterone acetate (CPA) and drospirenone (DRSP) have been proved effective for the treatment of acne and facial hirsutism. This study prospectively compared the clinical and biochemical efficacy of 3 mg DRSP/30 μg ethinyl estradiol (EE) and 2 mg CPA/35 μg EE combinations in a total of 91 patients with hirsutism. Individuals randomly received a cyclic combination of either DRSP/EE (n = 48) or CPA/EE (n = 43) for 12 months. Basal serum total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and SHBG levels, as well as Ferriman–Gallwey scores, were determined before and after treatment. Both COCs achieved a similar effect on clinical hirsutism scores, in addition to serum androgen and SHBG levels, after completion of therapy. The percentage reductions in total hirsutism score (median % (min–max)) during therapy were 0.70 (0–0.58) vs. 0.57 (0.10–1.00) at 6 months (p = 0.028) and 0.80 (0–0.42) vs. 0.81 (0–0.75) at 12 months (p = 0.6) in the DRSP/EE and CPA/EE groups, respectively. In conclusion, the DRSP/EE combination is at least as effective as the CPA/EE combination in improving hirsutism scores.

Differential diagnosis of intra-uterine device migrating to bladder using radiographic image of calculus formation and review of literature.

A 28-year-old woman in whom a copper-T 280-A intra-uterine device (IUD) had been placed 6 months previously, presented complaining of urinary system infection and lower abdominal pain. Intra-vesical migration of IUD was confirmed by radiography and cystoscopy. Since 1966, 17 other cases of calculus formation among 41 cases of intra-vesical migration have been reported.

Long-term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels.

OBJECTIVE To determine the long-term effects of estrogen replacement therapy on sex hormone binding globuline (SHBG) and free testosterone (fT) levels in surgical postmenopausal women. STUDY DESIGN Forty patients with surgical menopause were enrolled in this prospective study. The women were randomly divided into two groups. The first group received oral therapy (continuous conjugated equine estrogens (CEE) - 0.625mg per day) and the second group received transdermal therapy (patches delivering continuous 17beta-estradiol (E2)--0.05mg per day). Serum SHBG and fT levels were determined at baseline and after first and second years of treatment. Two-way repeated measures analysis of variance with Bonferroni adjusted post-hoc test and unpaired-t-test were performed for statistical analysis with SPSS program. RESULTS Serum SHBG levels increased significantly with oral CEE after first year of treatment (P<0.05) and remained at this level for the next year. Transdermal therapy did not affect SHBG levels after first and second years (P<0.05). Serum fT levels did not change significantly in either group at the end of the first or second years (P<0.05) although there was a significant difference between the groups after 2 years (P<0.05). CONCLUSION Oral conjugated estrogens increased SHBG levels during therapy. This effect may balance the increased estrogen and androgen stimulation on breast tissue and may be more beneficial to the cardiovascular system in postmenopausal women.

The effects of metformin and letrozole on endometriosis and comparison of the two treatment agents in a rat model

BACKGROUND Our aim was to investigate the effects of metformin and letrozole on experimentally induced endometriosis in a rat model. METHODS Endometriotic implants were surgically formed, and 38 rats were randomly divided into four groups. Group 1 (control group, 8 rats) was given no medication. Group 2 (metformin group, 10 rats) was given 100 mg/kg/day of oral metformin. Group 3 (metformin group, 10 rats) was given 200 mg/kg/day of oral metformin. Group 4 (letrozole group, 10 rats) was given 0.1 mg/kg/day of oral letrozole. All rats continued to receive the treatment for 4 weeks and then were sacrificed to assess the size of implants and scores of adhesions. The histopathologic scores of implants in excised endometriotic foci were examined by a pathologist. RESULTS The mean surface area of endometriotic implants was similar in all groups before the treatment. Although the area was not reduced in controls, it was found to be significantly reduced in all treatment groups (44.50 +/- 23.37, 5.90 +/- 2.37, 4.30 +/- 1.33, 6.90 +/- 3.72 mm(2), respectively; P < 0.05). The effect was comparable between the treatment groups. The histopathologic assessment revealed that the histopathologic score of implants was lowest after 100 mg/kg/day metformin. Additionally, metformin reduced the severity of adhesions. CONCLUSIONS Metformin and letrozole caused a statistically significant regression of endometriotic implants. The effects of metformin on endometriotic tissue were at least comparable to letrozole.

Prevention of paclitaxel and cisplatin induced ovarian damage in rats by a gonadotropin-releasing hormone agonist.

OBJECTIVE To evaluate the protective effect of GnRH agonist for the prevention of ovarian reserve during treatment with paclitaxel and cisplatin. DESIGN Experimental study. SETTINGS University-based research laboratory. ANIMAL(S) Seventy female Wistar-Albino rats. INTERVENTION(S) Each group consisted of 10 rats. Group 1 served as controls. Groups without GnRH agonist (groups 2, 3, and 4) were administered paclitaxel and cisplatin, respectively; the remaining groups (groups 5, 6, and 7) were given the same regimens with GnRH agonist. The GnRH agonist (leuprolide acetate; 2.5 microg/d subcutaneously for 5 weeks) was started four weeks before chemotherapy to achieve anovulation. Paclitaxel (7.5 mg/kg) and cisplatin (5 mg/kg) were administered intraperitoneally on the 28th day as a single dose. MAIN OUTCOME MEASURE(S) One week after the chemotherapy, the animals were euthanized and primordial, primary, secondary, and tertiary follicle counts were evaluated. RESULT(S) Primordial, primary, and tertiary follicle counts in group 5 (paclitaxel plus GnRH agonist) and tertiary follicles in groups 2 and 3 had not decreased, but there was a significant decrease in other treatment groups compared with controls (P < 0.05). Binary comparison between all groups demonstrated that the primordial follicle count in group 5 was comparable to those of the controls. CONCLUSION(S) Paclitaxel plus GnRH agonist treatment may be an appropriate option for patients deserving further fertility in the preservation of primordial follicles.

New alternative treatment in hirsutism: bicalutamide 25 mg/day

The efficacy of low-dose bicalutamide (25 mg/day) in the treatment of hirsutism was investigated in this study. Hirsutism score was determined, according to a modified Ferriman-Gallwey scoring system, in 42 women with hirsutism. Each patient received 25 mg/day bicalutamide. Before therapy, multiscreen blood chemistry, hormonal analysis, and complete blood counts were performed. These parameters and hirsutism scores were repeated at 3 and 6 months during therapy. The paired Students t-test was used to compare repeated values. Clinical improvement in the degree of hirsutism was observed in all patients by the same author. The modified Ferriman-Gallwey scores decreased from a mean of 22.0 ± 5.1 to 8.6 ± 3.5 (p < 0.0001). The reduction in hirsutism scores was 41.2 ± 11.4% at 3 months and 61.6 ± 11.1% at 6 months. In conclusion, bicalutamide at 25 mg/day is an effective drug in the treatment of patients with hirsutism.

Effects of hypertension and obesity on endometrial thickness.

OBJECTIVE The aim of this study was to evaluate the effects of hypertension and obesity on endometrial thickness. STUDY DESIGN Forty obese women with hypertension (Group 1), 28 non-obese women with hypertension (Group 2), 58 obese women (Group 3), 56 non-obese healthy women (Group 4), totally 182 postmenopausal women were included in this prospective study. All patients were examined, and Papanicolaou cervical smear was performed after interview. Endometrial thickness was measured in the anterior-posterior diameter by vaginal ultrasonography. The data were analysed with one-way analyses of variance (ANOVA), Scheffe and chi2 tests. P<0.05 was accepted as statistically significant. RESULTS Endometrial thickness in obese women with or without hypertension were significantly greater than in non-obese women with or without hypertension (P<0.05). There was no statistical difference between non-obese hypertensive women and control group regarding endometrial thickness measurement (P>0.05). CONCLUSION Obesity has been found to increase endometrial thickness independently. Hypertension may increase the endometrial thickness if it is combined with obesity.

Doppler ultrasound assessment and serum cancer antigen 125 in the diagnosis of ovarian tumors.

Objective: To differentiate benign from malignant ovarian tumors based on sonographic detection of a solid component. Method: Sixty‐three women with ovarian masses were evaluated preoperatively by grayscale and power/color Doppler ultrasonographic examination, with specific predefined criteria for the solid component. Sensitivity, specificity, and positive and negative predictive values were calculated and assessed against the histopathologic outcome. The contribution of cancer antigen (CA) 125 levels to the diagnostic accuracy was also assessed. Result: Sensitivity, specificity, and positive and negative predictive values were 100%, 95.2%, 91.3% and 100%, respectively, with two false‐positive results. Had an elevated CA 125 level (> 35 U/mL) been included in the malignancy criteria, the false‐positive results would have been eliminated, giving an accuracy of 100%. Conclusion: Sonographic evaluation with predefined specific criteria for the detection of a solid tumor component is an accurate method of preoperative discrimination between benign and malignant ovarian tumors. A serum CA 125 assay may assist in eliminating false‐positive results.

Serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women

Aims. The aims of the present study were to determine the serum concentrations of insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin and insulin resistance in benign and malignant epithelial ovarian tumors, and to discuss the use of these markers in benign–malignant tumor differentiation. Methods. Forty-seven postmenopausal women with ovarian tumor and 31 age-matched, postmenopausal, healthy controls were included in this study. Insulin resistance index by homeostasis model assessment (HOMA score) and fasting blood glucose (FBG), serum IGF-I, IGFBP-3, leptin and CA-125 concentrations were determined in all patients preoperatively. The results were evaluated according to postoperative histopathology results. Results. According to postoperative histopathology results, the patients were divided into malignant (n = 23), benign (n = 24) and control (n = 31) groups. There were no differences among the groups in relation to age, body mass index, FBG and HOMA score (p > 0.05). Serum concentrations of CA-125 were elevated in the malignant group compared with the benign ovarian tumor and control groups (p < 0.05). In contrast, serum IGF-I concentrations were significantly decreased in patients with malignant and benign ovarian tumors compared with controls (p < 0.05). Serum IGFBP-3 concentrations were also found to be lower in women with malignant ovarian tumors than in women with benign tumors (p < 0.05). Serum leptin did not differ among patients with malignant–benign tumors and controls (p > 0.05). Conclusion. Serum leptin and HOMA score have not been found to be valid indicators in ovarian tumors. However, the present data suggest that low concentrations of IGF-I and IGFBP-3 could be a reliable marker to differentiate benign from malignant ovarian tumors. Further experimental studies are warranted to understand the impact of the IGF-I system in ovarian carcinogenesis.