Reduced progesterone action during endometrial maturation: a potential risk factor for the development of endometriosis

OBJECTIVE: To discuss the role that reduced endometrial responsiveness to progesterone (P) might play in the pathophysiology of endometriosis. DESIGN: A review of experimental evidence regarding the failure of P to regulate the expression of matrix metalloproteinases (MMPs) in the endometrium of patients with endometriosis. CONCLUSION(S): Progesterone and locally produced differentiation factors act cooperatively to reduce MMP expression by maternal endometrial cells within the pro-inflammatory micro-environment of early pregnancy. Our in vitro studies with normal human endometrium demonstrate that prior P exposure not only down-regulates MMP expression, but also limits the ability of locally produced proinflammatory cytokines to stimulate expression of these enzymes. In contrast, endometrial tissues from women with endometriosis demonstrate an altered response to P, allowing a continuous expression of MMPs throughout the secretory phase. Although the factors that influence the loss of P sensitivity in the endometrium of patients with endometriosis have not yet been defined, alterations in cell-cell communication seem to contribute to dysregulated MMP expression. Specifically, proinflammatory cytokines produced by epithelial cells oppose stromal cell responses to P, inhibiting production of key differentiation factors necessary for cell-specific MMP regulation. The resulting loss in normal MMP regulation enhances the invasive capacity of endometrial tissue, promoting ectopic establishment in an experimental model.     

生殖活动与子宫内膜异位症发病的关系

通过对２０３例盆腔子宫内膜异位症（异位症）病例和４０６例随机抽样对照人群的流行病学调查，发现生殖活动可能减少异位症的发生。曾足月妊娠分娩１次即可使发病相对危险度（ＲＲ）下降为０．３４；两次以上者的ＲＲ值降至０．０８。妊娠次数对发病尤明显的保护作用。人工流产和口服避孕药与发病无明显的相关性。不孕患者发病的相对危险度明显增高，但二含之间的因果关系尚不明确。初孕年龄对异位症的发病未发现有何影响。     

Obesity as a risk factor for development and poor prognosis of breast cancer

The evidence that obesity adversely affects women's health is overwhelming and indisputable. The risk of postmenopausal breast cancer increases with obesity; measured as weight gain, body mass index, waist-hip ratio or percent body fat. It is also established that obesity is associated with poor prognosis of breast cancer. This review examines in detail the possible mechanisms by which obesity causes poor prognosis of breast cancer such as estrogenic activity, advanced or more aggressive disease at diagnosis and high likelihood of both local and systemic treatment failure. After careful consideration of the available evidence, the author concludes that obesity contributes towards development and poor prognosis of breast cancer; therefore, weight management should be an integral part of any strategy to prevent and improve the outcome of breast cancer.     

Vascular endothelial growth factor gene polymorphisms and endometriosis risk: a meta-analysis

Purpose

The vascular endothelial growth factor (VEGF) gene polymorphism has been reported to be associated with endometriosis risk. The purpose of the present study was to perform a comprehensive meta-analysis to explore whether VEGF gene polymorphisms confer risk to endometriosis.

Methods

By searching PubMed and EMBASE databases, a total of 11 studies were identified. Crude odds ratio (OR) and their corresponding 95% confidence intervals (CI) for VEGF gene polymorphisms and endometriosis risk were calculated.

Result

An association of VEGF gene +936TC polymorphism with endometriosis was found (Fixed-effect model: TT?+?TC vs. CC: OR 1.184, 95% CI 1.027?C1.366, P?=?0.020; TC vs. CC: OR 1.187, 95% CI 1.024?C1.375, P?=?0.023. Random-effcet model: TT?+?TC vs. CC: OR 1.203, 95% CI 1.003?C1.443, P?=?0.046; TC vs. CC: OR 1.188, 95% CI 1.021?C1.382, P?=?0.026). No association between VEGF genes ?460CT, +405CG, ?2578AC, ?1154GA polymorphisms and endometriosis was observed.

Conclusion

Our results indicate that VEGF +936TC gene polymorphism is a risk factor for endometriosis, and not ?460CT, +405CG, ?2578AC, ?1154GA.     

Obesity as a risk factor for endometrial cancer

The epidemiology and risk factors for endometrial cancer are reviewed, with current data. Obesity seems to be the main risk factor for this neoplasia, both because it is very common in the female population, and because the other risk factor (i.e. estrogen replacement therapy) has almost disappeared with the addition of progesterone therapy. The pathogenesis of obesity as risk factor, although it is not completely clear and unique, is examined.     

Mammographic density: a hormonally responsive risk factor for breast cancer

Mammographic density refers to radiologically dense breast tissue, and reflects variations in the tissue composition of the breast. It is positively associated with collagen and epithelial and non-epithelial cells, and negatively associated with fat. There is extensive evidence that mammographic density is a risk factor for breast cancer, independent of other risk factors, and is associated with large relative and attributable risks for the disease. The epidemiology of mammographic density, notably the inverse association with age, is consistent with it being a marker of susceptibility to breast cancer. Cumulative exposure to mammographic density may be an important determinant of the age-specific incidence of breast cancer in the population. All risk factors for breast cancer must ultimately exert their influence by an effect on the breast, and these findings suggest that, for at least some risk factors, this influence includes an effect on the number of cells and the quantity of collagen in the breast, which is reflected in differences in mammographic density. Many of the genetic and environmental factors that influence the risk of breast cancer affect the proliferative activity and quantity of stromal and epithelial tissue in the breast, and these effects are reflected in differences in mammographic density among women of the same age. Some of these influences include endogenous and exogenous hormones, and the menopause. A better understanding of the factors that influence the response of breast tissue to these hormonal exposures may lead to an improved understanding of the aetiology of mammographic density and of breast cancer.     

Abnormal cervical cytology: a risk factor for endometrial cancer recurrence

The objective of this study was to evaluate the relationship between cervical cytology, histologic type, and risk of endometrial cancer recurrence. We performed a retrospective study of patients undergoing surgery for endometrial carcinoma. Risk factors for recurrence including histology, tumor grade, nodal status, myometrial invasion, peritoneal washings, stage, and cervical cytology were assessed. Abnormal cervical cytology was defined as the presence of any endometrial cells on Pap smear. Papillary serous and clear cell carcinomas were considered high-risk histologies. Univariate and multivariate analyses of risk factors for recurrence were performed. Thirty-nine (9%) patients developed recurrent endometrial cancer. More patients with abnormal Pap smears recurred (12% versus 4%, P < 0.05). For endometrioid adenocarcinoma, abnormal cervical cytology occurred in 61% and 7% recurred, while with high-risk histologies, 84% had abnormal cervical cytology and 19% recurred (P < 0.05). Other significant predictors of recurrence on univariate analysis were myometrial invasion, nodal status, washings, stage, and histology. On multivariate analysis, only nodal status remained a significant predictor of recurrence. Abnormal cervical cytology is associated with increased risk of endometrial cancer recurrence. Abnormal cervical cytology occurs more frequently in high-risk histologies, which are known to have a higher risk of recurrence. On multivariate analysis, only nodal spread remains a significant predictor of recurrence.     

Preterm premature rupture of the membranes: a risk factor for the development of abruptio placentae

A retrospective study of 298 patients with preterm premature rupture of the membranes managed expectantly during a 3-year period investigated the association between preterm premature rupture of the membranes and abruptio placentae. Expectant management was associated with the development of abruptio placentae in 19 of these 298 patients (6.3%). The prevalence of abruptio placentae in the entire population during the same 3-year period was 2.7%, whereas in patients without preterm premature rupture of the membranes it was 2%. None of the patients developed clinical or laboratory evidence of disseminated intravascular coagulation and no infection (maternal or neonatal) was noted among the patients who had abruptio placentae. Patients with preterm premature rupture of the membranes and severe oligohydramnios (largest pocket less than 1 cm) seem to be at particular risk for developing this complication. These data suggest that abruptio placentae should be considered as one of the possible risks of expectant management in preterm premature rupture of the membranes.     

Elevated plasma homocysteine in early pregnancy: a risk factor for the development of severe preeclampsia

OBJECTIVE: The aim of our study was to determine if an elevated plasma homocysteine level in early pregnancy is associated with the development of severe preeclampsia. STUDY DESIGN: Blood samples were obtained from patients attending their first antenatal visit. Cases were asymptomatic women who subsequently developed severe preeclampsia. Controls were matched for gestational age and date of sample collection. Plasma homocysteine level was measured by using fluorescence polarization immunoassay. RESULTS: There were 56 patients with severe preeclampsia from whom blood samples were obtained at a mean (+/-SD) gestation of 15.3 weeks (+/-4.04 weeks) and 112 controls at 14.9 weeks (+/-3.41 weeks). The preeclampsia cases had a mean (+/-SD) homocysteine level of 9.8 micromol/L (+/-3.3 micromol/L), whereas controls had a mean homocysteine level of 8.4 micromol/L (+/-1.9 micromol/L), P < or = .0001. CONCLUSION: Women who develop severe preeclampsia have higher plasma homocysteine levels in early pregnancy than women who remain normotensive throughout pregnancy. An elevated plasma homocysteine level in early pregnancy can increase the risk of developing severe preeclampsia by almost threefold.     

Pelvic inflammatory disease is a risk factor for cervical cancer

The acquisition of human papillomavirus (HPV), the most important etiological agent of cervical cancer, does not cause clinical complaints. Although HPV spreads together with agents causing pelvic inflammatory disease (PID) with complaints forcing the patient to seek medical advice, PID has not yet been evaluated as a predictor of cervical cancer. The present study aimed to determine the relationship between PID and HPV in order to evaluate the possible risk factor role of PID for cervical cancer. Two groups of patients were studied: (i) 2,215 women with PID; (ii) 4,217 women participating in a cervical cancer screening programme who were found to have cytological atypia, mucopurulent cervicitis or other colposcopically detected disorders but were free of symptoms of PID. The presence of HPV and other STD agents in cervical smears was detected with polymerase-chain reaction. HPV prevalence was 33.74% in patients with PID and 26.40% in the group of women without PID (p < 0.001). This suggests that patients suffering from PID apparently have a higher risk of cervical cancer.     

Diabetes as a risk factor for death following endometrial cancer

OBJECTIVE: To determine whether several personal or lifestyle risk factors for the occurrence of endometrial cancer are also risk factors for death following endometrial cancer. METHODS: In 1986, we obtained risk factor information by mail on 41,836 women aged 55-69 years and living in Iowa. We followed those initially free of cancer through 2000 and identified incident endometrial cancers via linkage to a cancer registry. Women with endometrial cancer (n = 415) then were followed to identify overall and endometrial cancer deaths. RESULTS: Over a median of 6.4 years following endometrial cancer diagnosis, 93 women died, 39 with endometrial cancer as the underlying cause. Among the various personal and lifestyle risk factors examined, only diabetes (self-reported) was related to death following endometrial cancer. Adjusted for age and extent of endometrial cancer at diagnosis, the relative risk of overall death for diabetic versus nondiabetic women was 2.79 (95% CI 1.63-4.78). For endometrial cancer as a specific cause of death, the diabetes-related relative risk was 2.38 (95% CI 1.05-5.37). Further adjustment for tumor grade strengthened these relative risks slightly. CONCLUSIONS: Diabetes is associated with poorer survival after incident endometrial cancer, independent of tumor stage and grade. Our findings raise the possibility of a diabetes-related condition, such as hyperglycemia or hyperinsulinemia, contributing to poorer endometrial cancer survival.     

Elevated plasma homocysteine in early pregnancy: a risk factor for the development of nonsevere preeclampsia

OBJECTIVE: We have recently demonstrated that an elevated plasma homocysteine in early pregnancy is associated with the development of severe preeclampsia. The aim of this study was to determine whether an elevated plasma homocysteine in early pregnancy is also associated with the development of nonsevere preeclampsia.STUDY DESIGN: Blood was obtained from patients attending for a first antenatal visit. Subjects were asymptomatic women who subsequently developed nonsevere preeclampsia. Controls were matched for parity, gestational age, and date of sample collection. Plasma homocysteine was measured using fluorescence polarization immunoassay.RESULTS: There were 71 cases of nonsevere preeclampsia sampled at a mean gestational age (±SD) of 15.9±3.6 weeks and 142 controls at 15.6±3.4 weeks. The preeclampsia cases had a mean (±SD) homocysteine level of 8.4±2.4 μmol/L, whereas controls had a mean homocysteine of 7.07±1.5 μmol/L (P≤.0001).CONCLUSION: Women who develop nonsevere preeclampsia have higher plasma homocysteine levels in early pregnancy compared with women who remain normotensive throughout pregnancy. An elevated plasma homocysteine value in early pregnancy may be associated with a 4-fold increased risk for development of nonsevere preeclampsia.     

MTHFR C677T polymorphism was an ethnicity-dependent risk factor for cervical cancer development: evidence based on a meta-analysis

Introduction

Many studies have studied the associations between 5, 10-methylene tetrahydrofolate reductase (MTHFR) polymorphisms and susceptibilities of cervical cancer and cervical intraepithelial neoplasia (CIN); however, the results were inconsistent. The aim of this study was to further assess the relationships by the method of meta-analysis.

Materials and methods

Two investigators independently searched the PubMed, Embase, Wang Fang (Chinese database) and CNKI (China National Knowledge Infrastructure), with latest update to July 1st, 2011. The pooled odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the strength of the associations by using fixed- or random-effect model.

Results

Ten case–control studies were included in this meta-analysis including a total of 1,803 cervical cancer or CIN cases and 2,363 controls. Pooled analyses showed that T allele of MTHFR C677T was significantly associated with increased CIN risk [OR (95 % CI): 1.28 (1.03–1.50) for CT vs. CC], especially for low-grade CIN risk. In addition, MTHFR C677T rather than A1298C polymorphism was associated with risk of cervical cancer. Stratifying analyses for ethnicity indicated that T allele of MTHFR C677T was associated with increased cervical cancer risk for Asian [OR (95 % CI): 1.56 (1.17–2.08) for TT vs. CC; 1.53 (1.19–1.96) for TT vs. C carriers] while decreased risk for Caucasian [OR (95 % CI): 0.63 (0.45–0.89) for TT vs. CC; 0.66 (0.56–0.79) for T carriers vs. CC].

Conclusion

This meta-analysis suggested that there was no association between MTHFR A1298C polymorphism and cervical cancer risk. However, MTHFR C677T was an ethnicity-dependent risk factor for cervical cancer occurrence. In addition, T allele of C677T was significantly associated with risk of low grade of CIN incidence. Because of modest limitations of our study, well-designed studies with large sample size were needed to confirm our findings in the future.     

Psychosexual behavior as a risk factor for cervix cancer]

Seventy-two patients with cervical cancer (n = 24), ovarian cancer (n = 24), or no disease (n = 24) were questioned about sexual activity and personal relationships. The interviews were conducted in a semistandardized fashion according to the Tübingen Sexual Therapy Scale. Patients with invasive cervical cancer did not have a larger number of sexual partners, an earlier age of first intercourse, greater sexual activity or less stable relationships than patients with ovarian cancer of healthy women. There was no statistical difference among the groups with regard to the relationships. However, patients with cervical cancer reported greater degrees of satisfaction with both sexuality and relationships.