Miller, Virginia M.

Many basic, mechanistic studies of how sex steroids alter vascular function proceeded from Dr. Bush's seminal epidemiologic observations that noncontraceptive use of estrogen reduced all-cause and cardiovascular mortality. However, translating findings from these basic science studies into clinical trials and clinical guidelines has been controversial. This commentary reviews the development of sex steroid vascular research, identifies mechanisms by which sex steroids affect vascular function, reviews findings from recent clinical hormone trials, and identifies challenges and the need for continued funding of such investigations.

In this report, sex/gender research relevant to reproduction on Earth, in conjunction with the extant human and animal observations in space, was used to identify knowledge gaps and prioritize recommendations for future sex- and gender-specific surveillance and monitoring of male and female astronauts. With overall increased durations of contemporary space missions, a deeper understanding of sex/gender effects on reproduction-related responses and adaptations to the space environment is warranted to minimize risks and insure healthy aging of the men and women who travel into space.

Carotid intima-medial thickness (CIMT) allows for early detection of carotid atherosclerotic vascular disease. Using fuzzy logic techniques, we propose a model for calculating the risk for predicting CIMT using expert opinion and various factors associated with CIMT in recently menopausal women. Study participants were enrolled in the Kronos Early Estrogen Prevention Study (KEEPS), a four year study where participants were assigned to either oral or transdermal hormone therapy or to the placebo group. The fuzzy mathematical model uses five fuzzy logic methods to calculate this risk factor for CIMT, including the analytic hierarchy process (AHP) method, Guiasu method, Yen method, Dempster–Shafer (DS) method, and the set valued statistical method (SVSM). The four methods, AHP, Guiasu, Yen, DS, and SVSM, were correlated to each other according to the Pearson ranking method. In addition, results showed that the estrogen treatment groups showed a statically significant decrease in calculated CIMT risk compared to placebo when all the methods were combined together (p = 0.0017). Our fuzzy mathematical model provides the first fuzzy mathematical model to predict the risk of CIMT in recently menopausal women and menopausal hormone therapy may be beneficial in reducing this risk.

Free vascular endothelial growth factor (VEGF) is undetectable in plasma during human pregnancy. However, studies examining pregnant rats have reported both low (8–29 pg/ml) and high (527–1,030 pg/ml) free VEGF. These discrepancies cast uncertainty over the use of rat models to study angiogenic factors in pregnancy and preeclampsia. This study investigates methodological factors that may explain these discrepancies. Plasma VEGF in nonpregnant, day 7 pregnant, and day 19 pregnant rats was measured using rat and mouse ELISAs (R&D Systems). The rat ELISA detected VEGF in plasma from nonpregnant rats but not in plasma from day 19 pregnant rats. The mouse ELISA detected higher VEGF concentrations than the rat ELISA in every sample tested. This discrepancy was greater in day 19 pregnant rats (median: 2,273 vs. 0 pg/ml) than in nonpregnant (97 vs. 20 pg/ml) and day 7 pregnant (66 vs. 2 pg/ml) rats. Recovery of recombinant rat VEGF (rrVEGF) spiked into plasma from nonpregnant and day 7 pregnant rats was high for the rat ELISA (82–105%) but low for the mouse ELISA (17–22%). The rat ELISA did not recover rrVEGF in plasma from day 19 pregnant rats, suggesting that this ELISA measures free VEGF. The use of the rat versus mouse ELISA likely explains the differences in reported VEGF concentrations in pregnant rats. While the rat ELISA appears to measure free VEGF, plasma concentrations in nonpregnant and pregnant rats are below the assay sensitivity limit. As most previous studies of pregnant rats used the mouse VEGF ELISA, these data should be interpreted cautiously.