Long-Term Estrogen Therapy Improves Vascular Function in Male to Female Transsexuals

AbstractObjectives. This study sought to examine the effects of long-term estrogen therapy on vascular function in male to female transsexuals and to compare the findings with those observed in men and premenopausal women.Background. Gender differences in coronary artery disease have largely been attributed to the beneficial effects of estrogen on vascular function and plasma lipids in women. However, the effects of estrogen on the male vasculature have not been widely studied.Methods. We compared the effects of estrogen on vascular function in 14 male to female transsexuals, 14 age-matched men and 15 premenopausal women. Flow-mediated vasodilation and response to nitroglycerin were assessed in the brachial artery using noninvasive ultrasound.Results. Flow-mediated vasodilation was similar in transsexuals and women but greater than that in men ([mean ± SE] 11.5 ± 1.3% and 9.4 ± 1.1% vs. 5.2 ± 1.0% respectively, p < 0.005). Responses to nitroglycerin were also greater in transsexuals and women than in men (21.6 ± 1.7% and 21.0 ± 0.9% vs. 14.5 ± 1.2%, respectively, p = 0.0005). These differences persisted even after adjusting for vessel size. Despite similar total cholesterol levels, transsexuals had high density lipoprotein cholesterol levels similar to those in women and greater than those observed in men (1.76 ± 0.12 and 1.82 ± 0.11 mmol/liter vs. 1.35 ± 0.07 mmol/liter, respectively, p < 0.005). Moreover, triglyceride levels were greater in transsexuals than in men and women, and low density lipoprotein cholesterol (LDL-C) particle size was smaller (25.7 ± 0.2 nm vs. 26.2 ± 0.1 and 26.6 ± 0.1 nm, respectively, p = 0.0001). Serum testosterone (an index of estrogen therapy in transsexuals) was markedly suppressed in transsexuals and similar to that in women. Univariate analysis revealed that there was a strong inverse correlation between serum testosterone and flow-mediated vasodilation (rs= −0.48, p < 0.005). Multivariate analysis revealed that the best combination of predictors of flow-mediated vasodilation was serum testosterone, vessel size and LDL-C (R2= 0.3, p < 0.005).Conclusions. Long-term estrogen therapy appears to improve vascular function in male to female transsexuals and occurs despite higher triglyceride levels and the presence of small, dense LDL-C. The beneficial effects of estrogen are not gender specific or solely mediated through endothelium-derived nitric oxide.(J Am Coll Cardiol 1997;29:1437–44

Impact of a farmers\u27 market nutrition coupon programme on diet quality and psychosocial well-being among low-income adults: protocol for a randomised controlled trial and a longitudinal qualitative investigation

Introduction Low-income populations have poorer diet quality and lower psychosocial well-being than their higher-income counterparts. These inequities increase the burden of chronic disease in low-income populations. Farmers&rsquo; market subsidies may improve diet quality and psychosocial well-being among low-income populations. In Canada, the British Columbia (BC) Farmers&rsquo; Market Nutrition Coupon Programme (FMNCP) aims to improve dietary patterns and health among low-income participants by providing coupons to purchase healthy foods from farmers&rsquo; markets. This study will assess the impact of the BC FMNCP on the diet quality and psychosocial well-being of low-income adults and explore mechanisms of programme impacts. Methods and analysis In a parallel group randomised controlled trial, low-income adults will be randomised to an FMNCP intervention (n=132) or a no-intervention control group (n=132). The FMNCP group will receive 16 coupon sheets valued at CAD$21/sheet over 10&ndash;15 weeks to purchase fruits, vegetables, dairy, meat/poultry/fish, eggs, nuts and herbs at farmers&rsquo; markets and will be invited to participate in nutrition skill-building activities. Overall diet quality (primary outcome), diet quality subscores, mental well-being, sense of community, food insecurity and malnutrition risk (secondary outcomes) will be assessed at baseline, immediately post-intervention and 16 weeks post-intervention. Dietary intake will be assessed using the Automated Self-Administered 24-hour Dietary Recall. Diet quality will be calculated using the Healthy Eating Index-2015. Repeated measures mixed-effect regression will assess differences in outcomes between groups from baseline to 16 weeks post-intervention. Furthermore, 25&ndash;30 participants will partake in semi-structured interviews during and 5 weeks after programme completion to explore participants&rsquo; experiences with and perceived outcomes from the programme. Ethics and dissemination Ethical approval was obtained from the University of Calgary Conjoint Health Research Ethics Board, Rutgers University Ethics and Compliance, and University of Waterloo Office of Research Ethics. Findings will be disseminated through policy briefs, conference presentations and peer-reviewed publications. Trial registration number NCT03952338

A three-dimensional in vitro model of tumor cell intravasation

Metastasis is the cause of over 90% of all human cancer deaths. Early steps in the metastatic process include: the formation of new blood vessels, the initiation of epithelial-mesenchymal transition (EMT), and the mobilization of tumor cells into the circulation. There are ongoing efforts to replicate the physiological landscape of human tumor tissue using three-dimensional in vitro culture models; however, few systems are able to capture the full range of authentic, complex in vivo events such as neovascularization and intravasation. Here we introduce the Prevascularized Tumor (PVT) model to investigate early events of solid tumor progression. PVT spheroids are composed of endothelial and tumor cells, and are embedded in a fibrin matrix containing fibroblasts. The PVT model facilitates two mechanisms of vessel formation: robust sprouting angiogenesis into the matrix, and contiguous vascularization within the spheroid. Furthermore, the PVT model enables the intravasation of tumor cells that is enhanced under low oxygen conditions and is also dependent on the key EMT transcription factor Slug. The PVT model provides a significant advance in the mimicry of human tumors in vitro and may improve investigation and targeting of events in the metastatic process