Gender Medicine最新文献

Background

The influence on, or interaction of, sex and dietary genistein on serum markers of cardiovascular health and cardiovascular function remain unclear.

Objectives

Our purpose was to examine the effects of a genistein-containing diet (600 mg/kg food) (600G) and a genistein-free diet (0G), on cardiovascular risk parameters of male and female mice.

Methods

C57BL/6J mice were fed the diets for 1 month, after which time blood pressure, serum markers, and in vitro vascular reactivity was measured.

Results

Males fed the 600G diet gained significantly less weight than males fed the 0G diet (by 1.71 g); diet had no effect on female weight gain. Males fed the 600G diet also exhibited significantly elevated serum insulin (2.9 [0.5] vs 1.8 [0.4] ng/dL), and decreased serum glucose (0.15 [0.01] vs 0.24 [0.02] ng/dL) levels, resulting in a significant increase in the ratio of insulin to glucose; insulin and glucose levels were not changed by dietary genistein in females. Arterial pressure measurements from 0G-fed males were lower than other groups. However, basal vascular reactivity of isolated aortic rings was significantly increased by the 600G diet in both males (from 0.55 [0.03] to 0.94 [0.18] g) and females (from 0.45 [0.04] to 0.78 [0.09] g). Aortic wall thickness was not affected by diet. Norepinephrine-mediated contractility was also greater in aortic rings of male and female mice fed the 600G diet, and differences from the 0G diet persisted in the presence of L-NG-nitroarginine methyl ester but were completely accounted for by increased basal reactivity.

Conclusion

Our data indicate that 1 month of a 600G or 0G diet significantly alters vascular function independent of sex. In contrast, sex-dependent differences exist in well-established serum markers of cardiovascular health and disease.

Background

Little is known about health care costs associated with the metabolic syndrome (MetS).

Objective

We assessed annualized health care costs and health outcomes for both genders in different health care settings among representative Taiwanese elders.

Methods

The Nutrition and Health Survey in Taiwan (1999–2000) provided 1378 individuals aged 65 years or older with known MetS status. Nutrition and Health Survey in Taiwan files were linked to National Health Insurance records (1999–2006). Student t tests and multiple regression models were used to assess expenditures in total and in 6 services: inpatient, ambulatory care, dental care, traditional Chinese medicine, emergency care, and contracted pharmacy. The Cox model was used to assess gender effect on all-cause mortality and cardiovascular disease mortality, whereas logistic regression was used for that on cardiovascular disease hospitalization. The 5 MetS component costs were evaluated by multiple regressions.

Results

MetS affected 29% of men and 48% of women. After full adjustment, those with MetS had 1.30 (95% CI, 1.11–1.52), men had 1.43 (95% CI, 1.20–1.70), and women had 1.19 (95% CI, 0.93–1.52) times higher costs than those without MetS. Compared with no MetS, MetS costs were increased 2.94-fold for inpatient care (95% CI, 1.23–7.10) and 1.30-fold for ambulatory care for men (95% CI, 1.12–1.52), whereas ambulatory MetS costs were increased 1.28-fold for women (95% CI, 1.05–1.57). MetS was associated with higher risk of cardiovascular disease hospitalization in men (adjusted odds ratio, 1.76; 95% CI, 1.20–2.58) but not in women (adjusted odds ratio, 1.08; 95% CI, 0.67–1.75). Among those with MetS, all-cause and cardiovascular mortality were comparable between men and women. Of the MetS components, low HDL cholesterol had the greatest affect on costs, more so in men (2.23-fold) than women (1.58-fold).

Conclusions

In people with MetS, service costs were greater overall, significantly for men, but not women, and these increased costs were evident for men who experienced hospitalization, but not women. At the same time, cardiovascular and all-cause mortalities were not significantly different by gender in regard to MetS in Taiwanese elders.

Background

The intrarenal renin−angiotensin system contributes to hypertension by regulating sodium and water reabsorption throughout the nephron. Sex differences in the intrarenal components of the renin−angiotensin system have been involved in the greater incidence of high blood pressure and progression to kidney damage in males than females.

Objective

This study investigated whether there is a sex difference in the intrarenal gene expression and urinary excretion of angiotensinogen (AGT) during angiotensin II (Ang II)−dependent hypertension and high-salt (HS) diet.

Methods

Male and female Sprague-Dawley rats were divided into 5 groups for each sex: Normal-salt control, HS diet (8% NaCl), Ang II−infused (80 ng/min), Ang II−infused plus HS diet, and Ang II−infused plus HS diet and treatment with the Ang II receptor blocker, candesartan (25 mg/L in the drinking water). Rats were evaluated for systolic blood pressure (SBP), kidney AGT mRNA expression, urinary AGT excretion, and proteinuria at different time points during a 14-day protocol.

Results

Both male and female rats exhibited similar increases in urinary AGT, with increases in SBP during chronic Ang II infusion. HS diet greatly exacerbated the urinary AGT excretion in Ang II−infused rats; males had a 9-fold increase over Ang II alone and females had a 2.5-fold increase. Male rats displayed salt-sensitive SBP increases during Ang II infusion and HS diet, and female rats did not. In the kidney cortex, males displayed greater AGT gene expression than females during all treatments. During Ang II infusion, both sexes exhibited increases in AGT gene message compared with same-sex controls. In addition, HS diet combined with Ang II infusion exacerbated the proteinuria in both sexes. Concomitant Ang II receptor blocker treatment during Ang II infusion and HS diet decreased SBP and urinary AGT similarly in both sexes; however, the decrease in proteinuria was greater in the females.

Conclusion

During Ang II−dependent hypertension and HS diet, higher intrarenal renin-angiotensin system activation in males, as reflected by higher AGT gene expression and urinary excretion, indicates a mechanism for greater progression of high blood pressure and might explain the sex disparity in development of salt-sensitive hypertension.

Numerous studies have shown that female human beings exhibit lower blood pressure levels over much of their life span compared with their age-matched counterparts. This sexual dimorphism is apparent in human beings as well as most, if not all, mammals. However, after the onset of menopause blood pressure levels in women increase and become similar to those in men, suggesting an important role of sex hormones in the regulation of blood pressure. The lower blood pressure levels in premenopausal women are associated with a lower risk of development and progression of cardiovascular disease and hypertension compared with age-matched men. This clear female advantage with respect to lower incidence of cardiovascular disease no longer exists after menopause, again highlighting the importance of sex hormones in the pathophysiology of cardiovascular disease in both men and women. In fact, both estrogens and androgens have been implicated in the development of cardiovascular disease and hypertension, with estrogens, in general, being protective and androgens being detrimental. Although the exact mechanisms by which sex hormones contribute to the regulation of cardiovascular function and blood pressure are still being investigated, there is increasing evidence that modulating the activity of locally active hormonal systems is one of the major mechanisms of sex hormone actions in target organs, including the vasculature and kidneys. Indeed, several studies have demonstrated the importance of the interaction between sex hormones and the renin–angiotensin system in regulating cardiovascular function and blood pressure. Furthermore, the differential effects of estrogens and androgens on the expression and activity of the components of the renin–angiotensin system could possibly explain the sex differences in blood pressure levels and the development and progression of cardiovascular disease and hypertension.

Background

Abdominal aortic aneurysms (AAAs) differ in men and women. Women are older at diagnosis, have a higher risk of rupture, and worse outcome after surgery compared with men. The higher occurrence of AAAs in men accounts for the dominance of men in biomarker analyses.

Objective

The primary aim of this study was to investigate levels of established biomarkers for AAA in men and women, and the secondary aim was to compare biomarker levels in women with and without AAAs.

Methods

In this prospective case–control study, blood samples were collected from 16 women and 18 men with AAAs ≥5.5 cm, from 20 women with AAAs <5.5 cm, and from 18 women with peripheral artery disease (PAD). Plasma concentrations of matrix metalloproteinase (MMP) −2, −9, and −13; tissue inhibitor of MMP-1 (TIMP-1); plasminogen activator inhibitor 1 (PAI-1); high-sensitivity C-reactive protein (hsCRP); and estradiol levels were analyzed by ELISA. An ultrasound examination was performed in women with PAD to exclude an AAA.

Results

Age and other comorbid conditions were similar between men and women with AAAs. Women with AAAs had higher levels of MMP-9 compared with men with equally large AAAs (42.8 ng/mL vs 36.2 ng/mL, P = 0.036) and lower levels of estradiol (30.0 pmoL vs 86.5 pmol/L, P < 0.001). Women with AAAs had lower levels of MMP-9 compared with women without (59.5 ng/mL vs 132.6 ng/mL, P = 0.010). There was no significant difference in the plasma levels of MMP-2, MMP-13, hsCRP, PAI-1, TIMP-1, and estradiol between women with and without AAAs.

Conclusion

The higher levels of MMP-9 in women compared with men with equally large AAAs could suggest that MMP-9 is a biomarker related to the sex differences in aneurysm development. The lower levels of estradiol in women with AAAs compared with men suggest that the possible protective effect of endogenous estrogen cannot be explained by a difference in circulating levels of estradiol.

Background

Cardiovascular disease is seen at a younger age and at a higher prevalence in patients with type 1 diabetes than in the general population. It is well described that women with type 1 diabetes have a higher relative risk of cardiovascular disease than men with type 1 diabetes, unlike that seen in the general population. The pathophysiology behind this is unknown.

Objective

We performed a cross-sectional study to examine sex differences in cardiovascular disease risk factors in adolescents with type 1 diabetes between ages 13 and 20 years, compared with children of a similar age without type 1 diabetes.

Methods

All patients underwent a dual energy x-ray absorptiometry scan to measure body composition and a pulse wave test measure of arterial elasticity. Fasting serum lipid levels, apolipoprotein B, and apolipoprotein C-III levels were measured in each patient. Twenty-nine children with type 1 diabetes (10 girls, 19 boys) and 37 healthy children (18 girls, 19 boys) participated.

Results

Although no sex differences for body mass index (P = 0.91) and glycosylated hemoglobin (P = 0.69) were seen, girls with type 1 diabetes had a significantly higher percent trunk fat compared with boys (P = 0.004). No sex differences were found (P > 0.05) for percent trunk fat in adolescents without diabetes. There was no sex difference among any other cardiovascular risk factors in either children with or without diabetes.

Conclusions

Female adolescents with type 1 diabetes have more centrally distributed fat, which may contribute to their relatively higher cardiovascular disease risk. Attenuation of the central distribution of fat through exercise and dietary modifications may help ameliorate their subsequent cardiovascular disease burden.

Background

Aging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide.

Objectives

Our purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys.

Methods

We compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress.

Results

There was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability.

Conclusions

The kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3 or NOS1 alpha.