Passive smoking is associated with lower age at menopause.

OBJECTIVE: The aim of the study was to investigate the age at menopause in women exposed to passive smoking. METHODS: The study was designed as a case-control study. The main outcome measure was to compare the age at menopause of women exposed to second-hand smoking to non-exposed women. RESULTS: The age at menopause in the group exposed to second-hand smoking was significantly lower than that of women in the non-exposed group (47.0 ± 4.7 vs. 48.1 ± 5.2 years, p = 0.002). In regression analyses, the age at menopause had an inverse correlation with second-hand smoking, and a positive correlation with the mother's age at menopause. We further stratified women according to their smoking status. Women exposed to second-hand smoking who had never smoked had a significantly lower age at menopause than the non-exposed women only when the duration of exposure exceeded 20 years (46.6 ± 5.6 vs. 48.4 ± 3.7 years, p = 0.008). Furthermore, women who had never smoked and who were exposed to ≥ 10 cigarettes per day had a significantly lower mean age at menopause than non-exposed women who had never smoked. These differences were not observed among women who had ever smoked. CONCLUSIONS: Our findings suggest that earlier age at menopause should be added to the negative effects of passive smoking, in addition to increased risks for overall, cardiovascular and cancer mortality as well as increased risk for osteoporosis.

Clinicopathologic study of the putative precursor lesions of epithelial ovarian cancer in low-risk women.

Possible precursor lesions for epithelial ovarian cancer (EOC) have been defined in the ovaries of women with contralateral EOC, with breast cancer susceptibility gene (BRCA)-1 mutations, or with positive family history. We aimed to investigate the prevalence of these lesions in women without any recognizable risk and to correlate these lesions with clinical ovulatory markers. The study group consisted of 184 women who were operated for benign gynecological conditions. Patients were requested to fill a questionnaire about anthropometric characteristics and medical and reproductive history. Oophorectomy specimens were examined for presence of epithelial inclusion cysts (EIC), cortical invaginations (CI), stromal hyperplasia (SHPP), epithelial pseudostratification (EPS), and surface papillomatosis (SP). Women with EIC were older, had lower age at menarche, and had higher menarche-to-pregnancy and menarche-to-operation time. SHPP was found to be related with age, menarche-to-operation time, history, and the duration of oral contraceptive use. Women with SP had lower age at menarche, lower menopausal age, and longer duration of hormone replacement therapy. No significant correlations were established between CI and any clinical parameters. Only one patient had EPS. Our findings suggest that these lesions correlate closely with reproductive features. Exact mechanisms that lead to development of these lesions should be clarified before implying them as precursor lesions of EOC.

Expression of the c-Met in advanced epithelial ovarian cancer and its prognostic significance.

The purpose of this study was to evaluate the prognostic significance of c-Met expression in advanced cases of epithelial ovarian carcinoma. Paraffin-embedded tissues from 41 stage IIIC primary ovarian adenocarcinoma were stained immunohistochemically for c-Met expression. The expression of c-Met was correlated with conventional clinicopathologic parameters and with overall survival of the patients. c-Met expression was found in 60.9% of cases. This clinicopathologic study showed that epithelial ovarian carcinomas with c-Met expression had higher histologic tumor grade and were more frequently associated with para-aortic lymph node metastasis (P < 0.05). In multivariate analysis, c-Met expression remained as a statistically significant predictor for survival with histologic grade. The patients with stage IIIC epithelial ovarian cancers whose tumors expressed c-Met were more likely to have high-grade tumors, have more para-aortic lymph node involvement, and have a significantly worse overall survival than those whose tumors were c-Met negative. In conclusion, c-Met expression might be a potential prognostic marker for patients with advanced-stage epithelial ovarian cancers.

Glutathione-S-transferase P1 gene polymorphism and susceptibility to endometriosis.

BACKGROUND: Glutathione-S-tranferase (GST) is the part of the key phase II detoxifying enzyme system. Many studies have investigated the role of GSTM1 and GSTT1 gene polymorphisms in endometriosis. Although GSTP1 was found to be one of the most abundant types of GST in genital system, there are insufficient data about the importance of the role of GSTP1 gene polymorphism in endometriosis. METHODS: This case-control study involved 150 patients with endometriosis and 150 controls. The frequency of GSTP1 single nucleotide polymorphisms was evaluated using PCR and melting curve analysis. RESULTS: The proportion of GSTP1 ile/ile tended to be higher in patients with endometriosis than control group, although the difference was not significant [odds ratio (OR)=1.53; 95% confidence interval (CI)=0.95-2.46]. In contrast, GSTP1 val/val was significantly higher in control patients and seems protective for endometriosis (OR=0.10; 95% CI=0.02-0.42). CONCLUSION: The results of this study suggest that GSTP1 polymorphism might modulate the risk of endometriosis with significantly decreased risk for GSTP1 val/val and marginally increased risk for GSTP1 ile/ile. Further studies on not only the disease processes but also normal distribution of the enzyme in female genital tract may provide better understanding about the role of GST types and their polymorphs in endometriosis.

Evaluation of glucose metabolism and reproductive hormones in polycystic ovary syndrome on the basis of peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala genotype.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism has been suggested as a protective factor for polycystic ovary syndrome (PCOS). In this study, we aimed to investigate metabolic features and reproductive hormones in women with PCOS and compare these features with control women on the basis of Pro12Ala genotype. METHODS: This study involved 60 randomly selected women with PCOS and 60 controls. Main outcome measures were anthropometric measures, variables of glucose metabolism and reproductive hormones. All the patients were genotyped for Pro12Ala variant of PPAR-gamma2 gene. RESULTS: Patients with Pro12Ala polymorphism were more obese in both groups. Furthermore, they had lower fasting insulin levels, were less insulin-resistant and were less glucose-intolerant as demonstrated by 2 h glucose concentrations. However, there was no difference in reproductive hormone levels on the basis of Pro12Ala genotype. CONCLUSIONS: Both control women and women with PCOS had significant differences in glucose metabolism on the basis of PPAR-gamma2 Pro12Ala polymorphism. Pro12Ala variant may break the process that leads to PCOS in susceptible women, instead of being a direct causal relationship between Pro12Ala polymorphism and PCOS.

The importance of IRS-1 Gly972Arg polymorphism in evaluating the response to metformin treatment in polycystic ovary syndrome.

BACKGROUND: Recent evidence suggests that one of the modes of action of metformin may be through phosphorylation of the insulin receptor and insulin receptor substrates. With this in mind, we supposed that the G972A variant of insulin receptor substrate-1 (IRS-1) may modulate the response to metformin treatment in women with polycystic ovary syndrome (PCOS). METHODS: This preliminary study involved 60 randomly selected women with PCOS. All patients received dietary instructions and metformin 500 mg three times daily for 6 months. Main outcome measures were androgen levels, parameters of glucose and insulin metabolism and anthropometric variables. After a second evaluation of the patients at 6 months, they were genotyped for the Gly972Arg variant of the IRS-1 gene. RESULTS: Metformin had differential effects on fasting insulin levels, insulin resistance as demonstrated by homeostasis model assessment (HOMA), LH, total testosterone, dehydroepiandrosterone sulphate and free testosterone index on the basis of IRS genotype. The response to metformin therapy in other parameters was not different according to IRS genotype. CONCLUSION: There was a differential effect of metformin therapy in PCOS women on the basis of IRS genotype. This study may call attention to the importance of molecular markers in the management of women with PCOS.