Racial differences in endothelial function in postmenopausal women

Objective

Racial differences in cardiovascular mortality among women remain largely unexplained. Preliminary data suggest that African American and Caucasian differences in endothelial function may parallel differential cardiovascular disease (CVD) risk in women. To further study differences in endothelial function between African American and Caucasian women, we analyzed measures of brachial artery flow-mediated dilation (FMD) in women enrolled in the Cardiovascular Health Study (CHS).

Methods and results

Brachial artery FMD was measured in the fasting state using established ultrasound techniques in 1330 Caucasian and 297 African American female participants in CHS (mean age 78.4 ± 4.4 years). General linear models were used to compare FMD between African American and Caucasian women after adjusting for baseline brachial diameter, hypertension, diabetes, smoking, cholesterol, systolic blood pressure, body mass index, waist/hip ratio, age, education, income level; use of angiotensin-converting enzyme inhibitors, β-blockers, nitroglycerin, estrogens and lipid-lowering drugs; and presence of clinical or subclinical disease. Adjusted absolute change and percent change in brachial artery diameter was significantly reduced in African American women compared with Caucasian women (P < .0001 and P = .0002, respectively). Similar results were found when the women were stratified by history of CVD (− CVD, P = .02; + CVD, P = .001) and CVD or subclinical vascular disease (− disease, P = .01, + disease, P = .03).

Conclusions

In this cohort, brachial artery FMD was lower in African American women compared to Caucasian women, and this difference persisted after adjustment by multivariable analysis. The increased CVD risk in African American women may be related to impaired endothelial function. It remains to be determined whether African American women may uniquely benefit by interventions designed to improve endothelial health.     

Forearm endothelial function and bone mineral loss in postmenopausal women

It is widely believed that the vasculature plays an important role in bone remodeling. We investigated the relationship between forearm endothelial function and bone mass in the lumbar spine in early postmenopausal women without a history of smoking or diabetes mellitus. We studied the forearm resistance artery endothelial function in 110 Japanese women-52 postmenopausal women with normal spinal bone mineral density (BMD), 36 postmenopausal women with osteopenia, and 22 osteoporotic postmenopausal women. Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. BMD of the lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry. After adjustment for age, body mass index, years since the start of menopause, and basal FBF, women with osteoporosis had a lower maximal FBF response to reactive hyperemia (28.4 +/- 3.8 mL/min per 100 mL tissue) than those with normal BMD (39.8 +/- 2.8 mL/min per 100mL tissue) or osteopenia (35.6 +/- 2.5 mL/min per 100mL tissue) (P = 0.029). A significant increase in serum angiotensin-converting enzyme (ACE) activity (P = 0.042) and a significant decrease in the serum concentrations of nitrite/nitrate (P = 0.041) were noted in osteoporotic women compared to women with normal BMD or osteopenia. The present findings suggest that postmenopausal women with low BMD, especially those with osteoporosis, have impaired endothelial function in the forearm resistance arteries.     

Raloxifene,conjugated oestrogen and endothelial function in postmenopausal women

OBJECTIVES: To study the long-term effects of raloxifene, a potential designer oestrogen, and oestrogen monotherapy on endothelial function in healthy postmenopausal women. DESIGN: A 2-year double-blind, randomized and placebo-controlled study in an Academic Medical Center. Fifty-six hysterectomized but otherwise healthy postmenopausal women randomly received raloxifene hydrochloride 60 mg day-1 (n = 15) or 150 mg day-1 (n = 13), conjugated equine oestrogen (CEE) 0.625 mg day-1 (n = 15), or placebo (n = 13). MAIN OUTCOME MEASURES: Endothelial function as estimated from brachial artery flow-mediated, endothelium-dependent vasodilation and nitroglycerine-induced endothelium-independent vasodilation, and plasma levels of the endothelium-derived regulatory proteins, von Willebrand factor (vWF) and endothelin (ET). RESULTS: Raloxifene 60 mg did not significantly affect endothelial function. As compared with placebo, at 6 months of therapy, raloxifene 150 mg and CEE were associated with a mean increase in vWF of 25.5% point (95% CI 3.6-47.3) and 26.6% point (95% CI 6.9-46.3), respectively. At 24 months of therapy, raloxifene 150 mg was associated with a mean decrease in ET of 0.96 pg mL-1 (95% CI -1.57 to -0.36). Raloxifene nor CEE significantly affected endothelium-dependent and/or -independent vasodilation. CONCLUSIONS: Our results suggest that long-term therapy with raloxifene or oral CEE does not affect endothelium-dependent vasodilation in healthy postmenopausal women. Raloxifene 150 mg day-1 might have both positive and negative effects on endothelium. The clinical significance of these findings remains to be investigated.     

Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women

Background

Tamoxifen is a selective estrogen-receptor modulator shown to improve several cardiovascular risk factors in postmenopausal women with breast cancer. In animal studies tamoxifen inhibits the progression of atherosclerosis. Although the presence of a history with tamoxifen treatment is related to a lower intima-media thickness (IMT) of the common carotid artery, data from controlled follow-up studies are lacking to support this observation.

Methods

We examined 14 postmenopausal women with early stage breast cancer with indication for tamoxifen treatment (20 mg/d) and 13 healthy postmenopausal women. Flow-mediated dilatation (FMD) of the brachial artery, combined carotid IMT, and aortic pulse wave were measured before and 6 months after treatment in the tamoxifen group and at the same times in the control group.

Results

FMD and IMT were significantly increased and decreased, respectively, in the treatment group compared to the control group (FMD: +2.2% ± 0.9% vs +0.085% ± 1%, P = .012; IMT: −0.088 ± 0.03 mm vs +0.04 ± 0.03 mm, P = .018, mean ± standard error of the mean, treatment vs control group). These differences remained significant even when adjusted for age, duration of menopause, and cardiovascular risk factors. Low-density lipoprotein cholesterol was also significantly reduced after tamoxifen treatment.

Conclusions

Tamoxifen treatment slows the progression of atherosclerosis in postmenopausal women with breast cancer as assessed by changes in carotid IMT. An improvement in endothelial function and blood lipid profile may be the reason for this beneficial effect.     

Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women

OBJECTIVES: Large scale epidemiological studies suggest that hormone replacement therapy (HRT) reduces cardiovascular events in postmenopausal women. Improvement in endothelial function may contribute to this protective effect. DESIGN: In a prospective, double blind study, 61 healthy postmenopausal women were randomized to receive either oral continuous combined HRT [oestradiol 2 mg and norethisterone acetate (NETA) 1 mg per day] or placebo. Endothelial function, assessed by flow-mediated vasodilation (FMD) of the brachial artery and expression of soluble endothelial cell adhesion molecules (CAM) were determined before, after 3 and 6 months of therapy. RESULTS: The FMD was significantly improved in women on combined HRT (from 5.97% to 10.94% after 3 months and to 10.58% after 6 months; both P < 0.01 versus baseline values) and did not change in the placebo group (6.92% at baseline, 5.86% after 3 and 6.26% after 6 months). After 3 months of combined HRT, significant decreases of 24.6% for E-selectin and 13.9% for intercellular adhesion molecule-1 (ICAM-1) were observed (both P < 0.01 versus baseline values) and were sustained after 6 months of therapy, whilst no differences emerged in the placebo group. CONCLUSIONS: Oestradiol and norethisterone acetate improve endothelial function by both enhancing FMD and reducing the levels of soluble E-selectin and ICAM-1 in healthy postmenopausal women.     

Endogenous hormones and coronary heart disease in postmenopausal women

The association between serum levels of endogenous estrogens in postmenopausal women and the subsequent risk of coronary heart disease (CHD) was examined in a prospective case-control study nested within the New York University Women's Health Study (NYUWHS). The NYUWHS is a prospective cohort study of 14,274 healthy women enrolled between 1985 and 1991. A total of 99 women who were postmenopausal and free of cardiovascular disease at enrollment and who subsequently experienced CHD, defined as non-fatal myocardial infarction (MI), fatal CHD, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG), were matched 1:2 by baseline age, blood sampling date, and postmenopausal status to controls who remained free of CHD as of the date of diagnosis of the matching case. Biochemical analyses for total estradiol, estrone, percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), and SHBG were performed on pre-diagnostic stored serum samples. Participants had not used any hormone medications in the 6 months prior to blood collection. In the model adjusting only for matching factors, the risk of CHD in the top tertile of calculated bioavailable estradiol was elevated compared with the bottom tertile (OR=2.10; 95% CI=1.13-3.90, P for trend=0.03), and the risk in the top tertile of SHBG was reduced (OR=0.50, 95% CI=0.28-0.92, P for trend<0.01). However, these associations disappeared after adjusting for baseline hypertension status, body mass index, and serum cholesterol levels. These findings suggest that circulating estradiol and SHBG are not associated with CHD risk in postmenopausal women beyond what can be explained by the variation in hypertension status, BMI, and cholesterol.     

Endogenous sex hormones and glucose tolerance status in postmenopausal women

CONTEXT: In postmenopausal women, endogenous estradiol (E2) and free testosterone (T) have been positively associated with glucose intolerance and type 2 diabetes. Most studies have not examined these associations in a large group of postmenopausal women. OBJECTIVE: The objective was to examine the association between endogenous sex hormones and glucose tolerance in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 1973 postmenopausal women ages 45-84 yr, not taking hormone replacement therapy, in the Multi-Ethnic Study of Atherosclerosis baseline examination. MAIN OUTCOME MEASURES: Impaired fasting glucose (IFG) and diabetes were defined based on fasting blood sugar and/or treatment for diabetes. In women with normal glucose tolerance, insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Increasing quartiles of bioavailable T and E2 and decreasing quartiles of SHBG were associated with significantly increased odds of IFG and diabetes (all P for trend<0.001). Except for the association of bioavailable T with diabetes, the other associations persisted after multivariable adjustment. Although higher dehydroepiandrostenedione (DHEA) was associated with greater odds of IFG (P for trend=0.02), it was not associated with diabetes. Of 1100 women with normal glucose tolerance, E2 and DHEA were positively associated, and SHBG was inversely associated with HOMA-IR (all P<0.001) after multivariable adjustment. Bioavailable T was associated with HOMA-IR (P<0.001), but not fasting glucose. CONCLUSION: Of postmenopausal women, endogenous bioavailable T, E2, and DHEA were positively associated and SHBG was negatively associated with insulin resistance.     

Endogenous sex hormones and C-reactive protein in healthy postmenopausal women

Background. Oral oestrogen replacement therapy increases levels of C‐reactive protein (CRP). CRP is an established strong predictor of cardiovascular events. It is unknown whether endogenous oestrogen levels are associated with CRP. We therefore studied the relationship between endogenous sex hormones and CRP in healthy postmenopausal women emphasizing the role of body composition as peripheral fat is both a main source of oestrogen production after menopause and an endocrine tissue with inflammatory activities. Subjects and methods. The study population comprised 889 women participating in the PROSPECT study, an ongoing population‐based cohort study. Information on risk factors was collected by questionnaires and clinical examination. Endogenous sex hormone levels and CRP were measured with double antibody radio immuno assay (RIA) from fasting plasma samples. In this cross‐sectional study, associations between risk factors and lnCRP were studied using linear regression models. Results. Increases in oestrone and free oestradiol levels and the free androgen index were related to an increase in lnCRP of 1.19, 1.23 and 1.21 mg dL^?1 respectively. Body mass index (BMI), waist circumference and physical activity were strongly related to CRP levels, independent of age and other cardiovascular risk factors. Levels of all sex steroids but dehydroepiandrostenedione decreased with age. In age‐adjusted analyses, an increase in waist circumference or BMI by one quartile was associated with a 1.28‐fold and 1.26‐fold increase in CRP. The relationship between endogenous hormones and CRP was modestly attenuated but remained highly significant after adjustment for body composition, physical activity and other traditional cardiovascular risk factors. Conclusions. Our findings show that in postmenopausal women high levels of endogenous oestrogenic and androgenic sex steroids coincide with high CRP levels. This was only explained in part by markers of body composition or intra‐abdominal fat.     

Pharmacokinetics of a testosterone gel in healthy postmenopausal women

BACKGROUND: The paucity of pharmacokinetic data on androgen formulations in women has hindered clinical trials of testosterone supplementation in women. OBJECTIVE: The objective of this study was to determine the time course and profile of serum testosterone concentrations during treatment with different doses of testosterone gel in postmenopausal women and assess whether estrogen treatment affects the pharmacokinetics of testosterone gel. METHODS: Postmenopausal women with total testosterone levels less than 33 ng/dl after baseline 24-h sampling were treated with 4.4, 8.8, or 13.2 mg testosterone gel daily for 7 d each in random order, with a 7-d washout period between doses. We studied 13 women who had not received estrogen therapy (group I) and 13 who had received stable estrogen therapy for 3 months or more (group II). Total and free testosterone concentrations were measured for 48 h on the seventh day of each dose administration. RESULTS: Twenty-six women were randomized; of these, 24 were evaluable, 13 in group I and 11 in group II. The average steady-state concentrations (Cav) of serum total and free testosterone increased with increasing testosterone dose and were highly correlated with the dose (dose effect, P < 0.00001), but were not affected by estrogen therapy (P = 0.43). In both groups, the 4.4-mg dose increased Cav total and free testosterone into the mid- to high-normal range, whereas 8.8- and 13.2-mg doses raised total (Cav: 22.3, 51.6, 80.3, and 92.0 ng/dl in group I; 22.7, 59.8, 82.0, and 114.3 ng/dl in group II at 0, 4.4, 8.8, and 13. 2 mg, respectively) and free testosterone (5.9, 8.4, 11.5,12.8 pg/ml in group I and 5.0,7.6,11.1,10.8 in group II, respectively, at the various doses) above the physiological range. The area under the curve, maximum and minimum concentrations, and the change in Cav for total and free testosterone were dose related and significantly higher during administration of the 13.2-mg dose than during the 0- or 4.4-mg dose; estrogen therapy had no significant effect on these measures. Serum estradiol, LH, FSH, and SHBG levels did not change significantly at any dose. Testosterone gel was well tolerated. CONCLUSIONS: Administration of testosterone gel to postmenopausal women raised total and free testosterone concentrations in proportion to the administered dose without affecting estradiol levels. A 4.4-mg dose raised testosterone levels into the mid- to high-normal range. Previous estrogen therapy had no significant effect on testosterone pharmacokinetics over this short duration.     

Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women

BACKGROUND: Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objectives. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. METHODS: One hundred and five healthy postmenopausal women aged 52-67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Flow mediated dilatation was inversely related to the plasma logLp(a) level. Mean change per unit logLp(a) increase:-2.83% (95% CI: -5.22--0.43). Elevated Lp(a) (>239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4%+/-1. 2) compared to Lp(a) < or =239 mg/l (5.2%+/-0.7). Adjustment for other cardiovascular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) (< or =239 mg/l) (8.0+/-1.2 vs. 11.4%+/-0.8). CONCLUSION: Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women.     

利维爱对绝经后妇女氧化低密度脂蛋白及内皮功能的影响

目的 观察利维爱治疗对绝经后妇女血清氧化型低蜜度脂蛋白(ox-LDL)、一氧化氮(NO)、内皮素-1(ET-1)水平的影响.方法选择有更年期症状的绝经后妇女138例,随机分为利维爱组(利维爱2.5 mg/d)和对照组.利维爱组治疗前及治疗2年后检测血清ox-LDL、NO、ET-1水平.结果 129例完成观察和治疗.利维爱治疗2年后血ox-LDL(P＜0.01),ET(P＜0.05)显著降低,NO显著升高(P＜0.05).结论利维爱对动脉内皮细胞有保护作用,对预防动脉粥样硬化有效.     

Apolipoprotein E phenotype affects the malondialdehyde-modified LDL concentration and forearm endothelial function in postmenopausal women

OBJECTIVE: We investigated whether the apolipoprotein E (apo E) phenotype affects the serum concentration of malondialdehyde-modified low-density lipoprotein (MDA-LDL) or forearm endothelial function in postmenopausal women. PATIENTS AND MEASUREMENTS: Individuals were divided into three groups according to their apo E phenotype: E2 (E2/2 and E2/3, n = 12); E3 (E3/3, n = 71); and E4 (E3/4 and E4/4, n = 27). The serum concentrations of lipids and MDA-LDL were measured. Forearm blood flow during reactive hyperaemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. RESULTS: The serum concentrations of total and LDL cholesterol were significantly higher in the E4 group than in the E2 group (P < 0.05) or in the E3 group (P < 0.05). The serum apo B concentration was significantly higher in the E4 group than in the E2 group (P < 0.05). The serum concentrations of high density lipoprotein (HDL) cholesterol and nitrite/nitrate were significantly lower in the E4 group than in the E2 group (P < 0.05). Other lipid concentrations did not differ in the three groups. The serum MDA-LDL concentration was highest in the E4 group, and was lowest in the E2 group (E2: 91.1 +/- 6.9 IU/l, E3: 112.3 +/- 5.9 IU/l, E4: 128.8 +/- 9.9 IU/l; P < 0.05). The forearm blood flow response to reactive hyperaemia was lowest in the E4 group, and highest in the E2 group (E2: 52.2 +/- 5.8 ml/min per 100 ml tissue, E3: 40.7 +/- 1.7 ml/min per 100 ml tissue, E4: 33.4 +/- 2.4 ml/min per 100 ml tissue; P < 0.05). The forearm blood flow changes in response to nitroglycerine were similar between all three groups. CONCLUSIONS: The apo E phenotype affects the serum MDA-LDL concentration and forearm endothelial function in postmenopausal women.     

Relationship between endogenous testosterone and cardiovascular risk in early postmenopausal women

Cardiovascular disease (CVD) is the leading cause of death among postmenopausal women. Changes in endothelial function play an important role in the pathophysiology of atherosclerosis, and evidence suggests that interventions to improve endothelial function could modify the rates of progression and the risk of cardiovascular events. In addition, a positive association between markers of endothelial dysfunction and androgenicity has been described in women with polycystic ovary syndrome, suggesting a correlation with the early-onset endothelial dysfunction found in these patients. We performed a cross-sectional study to verify whether endogenous testosterone levels are correlated with markers of inflammation and endothelial function and with anthropometric and metabolic profile in 53 postmenopausal women. Serum testosterone, sex hormone-binding globulin, C-reactive protein (CRP), fibrinogen, and plasma endothelin-1 (ET-1) were determined. Patients were stratified into 2 groups (higher or lower than the mean testosterone levels of the studied sample). Mean age was 55 years (+/-5), and median time since menopause was 5.5 years (interquartile range, 3-8 years). Body mass index and waist circumference were significantly higher in the group with testosterone levels >or=0.49 ng/mL. Median CRP levels were greater in the group with higher testosterone levels (1.17 [0.17-2.36] vs 0.17 [0.17-0.61] mg/L, P = .039). Median ET-1 levels were also higher in women with greater testosterone levels (0.84 [0.81-0.97] vs 0.81 [0.74-0.84] pg/mL, P = .023). An association of testosterone with CRP (r = 0.416, P = .004) and ET-1 (r = 0.323, P = .031) was observed. This association was dependent on homeostasis model assessment index for ET-1 but not CRP. Testosterone was also associated with waist circumference and blood pressure (P = .001). These data suggest that endogenous testosterone levels in recently postmenopausal women may be part of a proatherogenic profile. Longitudinal studies are needed to assess if androgenicity represents a risk factor for cardiovascular disease and the clinical relevance of its association with ET-1 and CRP in this population.     

Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women

Plant estrogen or phytoestrogens (PE) are increasingly consumed for the purposes of menopause symptom relief and prevention of cardiovascular and other diseases. The objective of this study was to evaluate the effects of PE on plasma lipids and lipoproteins and on endothelial function. Twenty healthy, postmenopausal women, 50 to 70 years old, and with evidence of endothelial dysfunction, were treated with a soybean PE tablet of 80 mg/day of isoflavones. Endothelial function was assessed noninvasively using brachial ultrasound. A double-blind, placebo-controlled, randomized crossover design was employed. After 3 weeks stabilization on a standard fat-reduced diet, subjects received PE or placebo for 8 weeks in random order, separated by a washout period of 8 weeks. Compared with placebo, there were no significant effects of PE on blood pressure and plasma lipid or lipoprotein concentrations. Flow-mediated endothelium-dependent dilation (FMD) in response to reactive hyperemia was not significantly changed by PE ingestion (3. 3 +/- 0.7% on placebo vs 4.1 +/- 0.7% on PE, p >0.4). Variation in FMD was not correlated with change in plasma isoflavone concentration (r = -0.09, p >0.7). Glyceryl trinitrate endothelium-independent dilation was not significantly changed with PE (15.9 +/- 1.3% vs 13.7 +/- 1.2%, p >0.1). These results fail to show a significant impact of medium-term supplementation with 80 mg/day of isoflavones on lipid and lipoprotein levels or on endothelial function in healthy, postmenopausal women.     

Endogenous sex hormone levels in postmenopausal women with Alzheimer's disease

A cross-sectional study examined whether there was a difference in endogenous serum sex hormone levels between community-dwelling postmenopausal women with Alzheimer's disease (AD) and healthy controls. Total morning levels of serum estrone, estradiol, androstenedione, testosterone, and cortisol were measured in 52 nondepressed women with AD and 60 postmenopausal women who were neither depressed nor cognitively impaired. Estradiol was undetectable in 35.7% of cases, but detectable hormone was found in 96-100% of cases otherwise. After adjustment for potential confounds, serum levels were significantly higher for estrone (P = 0.0057) and androstenedione (P = 0.02), but not testosterone (P = 0.086) or estradiol (P = 0.59), in subjects with AD. Sex hormone levels did not correlate with cognitive scores in either group. Although the failure to detect estradiol in a third of cases limits the conclusions that can be drawn for this hormone, the possibility that AD is associated with abnormalities in certain serum sex hormone levels should be considered and warrants further research.     

Effects of testosterone treatment on endometrial proliferation in postmenopausal women

CONTEXT: Available data concerning effects of testosterone on endometrium of postmenopausal women are seriously limited. OBJECTIVE: Our aim was to compare the influence of treatment with testosterone and/or estrogen on endometrial proliferation in healthy postmenopausal women. DESIGN: This was an open, randomized clinical study with parallel comparison of the groups. SETTING: The study was conducted at a women's health clinical research unit and a research laboratory at a university hospital. PARTICIPANTS: Sixty-three women who had experienced natural menopause participated in this study. INTERVENTIONS: After random assignment, the participants were administered orally testosterone undecanoate (40 mg every second day), estradiol valerate (2 mg daily), or both for 3 months. MAIN OUTCOME MEASURES: Endometrial thickness was measured, and endometrial proliferation evaluated on the basis of histopathology and expression of Ki-67, a proliferation marker. RESULTS: Endometrial thickness was significantly increased by treatment with estrogen alone or in combination with testosterone but was unaltered by testosterone alone. Among the women receiving estrogen alone, the proportion exhibiting histopathology indicative of proliferation increased significantly to 50% (P < 0.05), there was a nonsignificant increase to 28% with the combined treatment, whereas testosterone alone had no effect at all. Expression of Ki-67 was up-regulated significantly in both glands and stroma (P < 0.05, respectively) in both estrogen treatment groups. However, the expression was significantly higher in stroma by estrogen treatment alone than after combined treatment (P < 0.05). CONCLUSIONS: The short-term treatment with testosterone of postmenopausal women does not stimulate endometrial proliferation. In addition, testosterone appears to counteract endometrial proliferation induced by estrogen to a certain extent.     

Physiological testosterone replacement and arterial endothelial function in men

OBJECTIVE: The vascular effects of fluctuations in testosterone levels within the physiological range in otherwise healthy men are not known. We therefore aimed to study arterial function in hypogonadal men receiving long-term physiological androgen replacement therapy, at trough and peak testosterone levels. PATIENTS AND DESIGN: We recruited nine hypogonadal men (aged 35 +/- 4 years) receiving androgen replacement therapy, each treated with 800 mg testosterone (T) depot preparations every 6 months. MEASUREMENTS: Serum lipid and hormone levels and arterial reactivity were measured, prior to (trough T) and 2-4 weeks following testosterone administration (peak T). Each subject therefore served as their own control. Vessel diameter was measured by ultrasound at rest, during reactive hyperaemia [leading to flow-mediated dilatation (FMD), an endothelium-dependent response] and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). RESULTS: Serum T (13 +/- 2 nmvs. 27 +/- 3 nm for trough and peak serum T, respectively, P < 0.001; normal adult male range 11-35 nm), and free T (195 +/- 23 pmvs. 510 +/- 93 pm, P < 0.005) significantly increased following subcutaneous depot T administration, as did serum oestradiol (100 +/- 10 pmvs. 175 +/- 9 pm, P = 0.001; normal adult male range < 250 pm). There was a significant decrease in FMD (3.6 +/- 1.1%vs. 3.0 +/- 0.8%, P < 0.01), but GTN responses were similar (9.5 +/- 0.8%vs. 10.4 +/- 1.0%, P > 0.2). Lipid, blood pressure and vessel diameter measurements were also similar before and after testosterone administration. CONCLUSION: Physiological replacement of testosterone is associated with decreased endothelium-dependent dilatation, in hypogonadal men.     

Relationship between brachial arterial endothelial function and lumbar spine bone mineral density in postmenopausal women.

BACKGROUND: Osteoporosis and endothelial dysfunction have been associated with atherosclerosis. The correlation between brachial arterial endothelial function and lumbar spine bone mineral density (BMD) in postmenopausal women will be investigated. METHODS AND RESULTS: The endothelial function in 85 postmenopausal women, including 28 women with normal spinal BMD, 27 women with osteopenia, and 30 women with osteoporosis were studied. Brachial arterial flow-mediated vasodilatation (FMD) after reactive hyperemia was assessed by ultrasonography. The BMD at the lumbar spine (lumbar 2 to 4 vertebrae) was measured by dual-energy X-ray absorptiometry. Age, years since menopause, and FMD were significantly greater in the osteoporosis group than in the normal BMD group (p<0.01, p<0.05, and p<0.05, respectively). The BMD was significantly lower in the osteoporosis group than in the osteoporosis or normal BMD group (both p<0.01). After adjusting for age and years since menopause, women with osteoporosis had significantly lesser FMD than those with normal BMD (p<0.05). The univariate linear regression analysis revealed that brachial arterial FMD was significantly positively correlated with BMD (r=0.31, p<0.01), but showed no significant association with other clinical variables. In multivariate regression analysis, the FMD was significantly positively correlated with BMD (p<0.01), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis might have impaired brachial arterial endothelial function, suggesting that brachial artery endothelial function might be associated with lumbar spine bone mass in postmenopausal women.