Superficial venous disease and combined hormonal contraceptives: a systematic review

AbstractBackgroundSuperficial venous disease, which includes superficial venous thrombosis (SVT) and varicose veins, may be associated with a higher risk of venous thromboembolism (VTE). Use of combined hormonal contraceptives (CHCs) has been associated with an increased risk of VTE compared with nonuse. Little is known about whether use of CHCs by women with superficial venous disease may further elevate the risk of VTE.ObjectivesTo investigate evidence regarding risk of VTE in women with SVT or varicose veins who use CHCs compared with non-CHC users.MethodsWe searched the PubMed database for all English-language articles published from database inception through September 2014. We included primary research studies that examined women with SVT or varicose veins who used CHCs compared to women with these conditions who did not use CHCs. Outcomes of interest included VTE (among women with SVT or varicose veins) and SVT (for those with varicose veins).ResultsTwo studies were identified that met inclusion criteria. One fair-quality case–control study reported an odds ratio (OR) for VTE of 43.0 (95% confidence interval [CI] 15.5–119.3) among women with SVT using oral contraceptives (OCs) compared with nonusers without SVT. The OR for VTE was also increased for women with SVT not using OCs (OR 5.1; 95% CI 2.8–9.5) and for women without SVT using OCs (OR 4.0; 95% CI 3.3–4.7), compared with nonusers without SVT. One fair-quality cohort study demonstrated that women with varicose veins had an increased rate of VTE with use of OCs (1.85 per 1000 women-years [WY]), compared with users without varicose veins (0.84 per 1000 WY), nonusers with varicose veins (0.31 per 1000 WY) and nonusers without varicose veins (0.19 per 1000 WY). This study also demonstrated that women with varicose veins had an increased rate of SVT with use of OCs (10.63 per 1000 WY), compared with nonusers with varicose veins (7.59 per 1000 WY), users without varicose veins (1.89 per 1000 WY) and nonusers without varicose veins (0.77 per 1000 WY).ConclusionTwo studies suggest increased risk of VTE among OC users with superficial venous disease; however, no definitive conclusions can be made due to the limited number of studies and limitations in study quality. Theoretical concerns need to be clarified with further research on whether the risk of significant sequelae from superficial venous disease among CHC users is related to clinical severity of disease and underlying factors

Hormonal contraception among electronic cigarette users and cardiovascular risk: a systematic review

Background: Women who use combined hormonal contraceptives and cigarettes have an increased risk for cardiovascular (CV) events. We reviewed the literature to determine whether women who use hormonal contraceptives (HC) and electronic cigarettes (e-cigarettes) also have an increased risk. Study Design: Systematic review. Methods: We searched for articles reporting myocardial infarction (MI), stroke, venous thromboembolism, peripheral arterial disease or changes to CV markers in women using e-cigarettes and HC. We also searched for indirect evidence, such as CV outcomes among e-cigarette users in the general population and among HC users exposed to nicotine, propylene glycol or glycerol. Results: No articles reported on outcomes among e-cigarette users using HC. Among the general population, 13 articles reported on heart rate or blood pressure after e-cigarette use. These markers generally remained normal, even when significant changes were observed. In three studies, changes were less pronounced after e-cigarette use than cigarette use. One MI was reported among 1012 people exposed to ecigarettes in these studies. One article on nicotine and HC exposure found both exposures to be significantly associated with acute changes to heart rate, though mean heart rate remained normal. No articles on propylene glycol or glycerol and HC exposure were identified. Conclusion: We identified no evidence on CV outcomes among e-cigarette users using HC. Limited data reporting mostly acute outcomes suggested that CV events are rare among e-cigarette users in the general population and that e-cigarettes may affect heart rate and blood pressure less than conventional cigarettes. There is a need for research assessing joint HC and e-cigarette exposure on clinical CV outcomes

Breast cancer risk and hormone receptor status in older women by parity, age of first birth, and breastfeeding: a case-control study.

BACKGROUND: Early age at first birth and multiparity reduce the risk of estrogen receptor-progesterone receptor (ERPR)-positive breast cancer, whereas breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers. METHODS: We used multivariable logistic regression analysis to investigate whether age at first birth ( or =25 years) and breastfeeding (ever/never) modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative cancer using 1,457 incident breast cancer cases and 1,455 controls ages > or =55 years who participated in the Women's Contraceptive and Reproductive Experiences Study. RESULTS: Women who gave birth before age 25 years had a 36% reduced risk of breast cancer compared with nulligravida that was not observed for women who started their families at an older age (P(heterogeneity) = 0.0007). This protective effect was restricted to ERPR-positive breast cancer (P(heterogeneity) = 0.004). Late age at first birth increased the risk of ERPR-negative cancers. Additional births reduced the risk of ERPR-positive cancers among women with an early first birth (P(trend) = 0.0001) and among women who breastfed (P(trend) = 0.004) but not among older mothers or those who never breastfed. In women with a late first birth who never breastfed, multiparity was associated with increased risk of breast cancer. CONCLUSIONS: These findings suggest that the effect of parity on a woman's long-term risk of breast cancer is modified by age at first full-term pregnancy and possibly by breastfeeding

Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women

Abstract Introduction The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality. Methods We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of ER examined here included the percentage of tumor cell nuclei positively stained for ER, ER Histo (H)-score, and a score based on an adaptation of an equation presented by Cuzick and colleagues, which combines weighted values of ER H-score, percentage of tumor cell nuclei positively stained for the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) results. This is referred to as the ER/PR/HER2 score. Results After controlling for age at diagnosis, race, study site, tumor stage, and histologic grade in multivariable Cox proportional hazards regression models, both percentage of tumor cell nuclei positively stained for ER (P trend = 0.0003) and the ER H-score (P trend = 0.0004) were inversely associated with breast cancer-specific mortality risk. The ER/PR/HER2 score was positively associated with breast cancer-specific mortality risk in women with ER + tumor (P trend = 0.001). Analyses by race revealed that ER positivity was associated with reduced risk of breast cancer-specific mortality in white women and black women. The two quantitative measures for ER alone provided additional discrimination in breast cancer-specific mortality risk only among white women with ER + tumors (both P trend ≤ 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (P trend = 0.01) and black women (P trend = 0.03) with ER + tumors. Conclusions Our data support quantitative immunohistochemical measures of ER, especially the ER/PR/HER2 score, as a more precise predictor for breast cancer-specific mortality risk than a simple determination of ER positivity

Relationship between migraine history and breast cancer risk among premenopausal and postmenopausal women.

Both migraine and breast cancer are hormonally mediated diseases, and it is biologically plausible that women with a history of migraine may have a reduced breast cancer risk. However, this relationship has only been assessed in a single relatively small study that was unable to assess the effect of migraine triggers, which are also well-established breast cancer risk factors (e.g., use of alcohol and exogenous hormones), on the inverse association observed. Utilizing data on 4,568 breast cancer cases and 4,678 controls who participated in a multicenter population-based case-control study in the United States, we evaluated the association between migraine history and breast cancer risk using unconditional logistic regression. Migraine history data were obtained from structured in-person interviews. Women with a history of migraine had a reduced risk of breast cancer [odds ratio, 0.74; 95% confidence interval (CI), 0.66-0.82]. This risk did not differ by menopausal status, age at migraine diagnosis, use of prescription migraine medications, or when analyses were restricted to women who avoided various migraine triggers (including alcohol, exogenous hormones, and smoking). These data support a previous finding that a history of migraine may be associated with a reduced risk of breast cancer. It extends the prior report in observing that this relationship holds for both premenopausal and postmenopausal women and is independent of exposure to common migraine triggers