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Cytokine pattern in postmenopause.

OBJECTIVE: The present study was undertaken to evaluate the pattern of serum cytokine production in postmenopausal women and the relationship with the hormonal status. A group of fertile women served as controls. METHODS: Eighty-two women in apparent good health, non-smokers and without a history of hormone replacement therapy, were enrolled for the study. The women were divided in two groups according to their hormonal status: fertile women (n=34, age 32 +/- 7 years) and postmenopausal women (n=48, age 54 +/- 8 years). Blood samples were withdrawn in the morning, after an overnight fast. RESULTS: Sex hormones (LH, FSH, Estradiol, Progesterone, DHEA, DHEA-S), as well as GH and IGF-1 levels, were significantly higher in the serum of fertile women as compared with their postmenopausal counterparts. Unlike IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, significant differences were observed in serum IL-6, IL-18, TNFalpha and TNFbeta between groups: both IL-6 and IL-18 were higher in postmenopausal women, while TNFalpha and TNFbeta were significantly lower. There was an inverse relationship between serum DHEA and DHEA-S levels and both IL-6 (r= -0.46, P<0.02) or IL-18 (r= -0.38, P<0.05) serum concentrations. CONCLUSIONS: Compared with fertile counterparts, women in postmenopause present an alteration in serum cytokine profile suggesting a prevalence of Th2 lymphocytes.

Adolescent↗

Beneficial effects of hormonal replacement therapy on chromium status and glucose and lipid metabolism in postmenopausal women.

OBJECTIVES: Postmenopausal women exhibit an increased incidence of cardiovascular diseases, and type 2 diabetes mellitus compared with younger women. However, women receiving hormonal replacement therapy (HRT) seem to be protected. Since chromium (Cr) functions in glucose, lipid and corticosteroid metabolism and these variables, as well as Cr status, decline with age, Cr status may be a contributing factor in the effects of hormone replacement therapy. Therefore, the objective of this study was to determine the effects of hormonal replacement therapy (HRT) on serum and urinary Cr, plasma lipids, glucose, fructosamine and the related hormonal variables, estradiol, insulin, leptin, cortisol, and DHEA-sulfate. METHODS: Forty-four healthy postmenopausal women 50-60 years old participated in the study. Eighteen were treated by combined oral hormonal replacement therapy (estradiol 2 mg per day during days 1-25 and 10 mg of dydrogesterone on days 10-25) for at least 2 years, and 26 were untreated. RESULTS: Serum Cr concentrations were significantly lower in untreated postmenopausal women than in women receiving HRT (0.070+/-0.008 vs. 0.100+/-0.008 ng/ml) whereas urinary Cr excretion was increased (0.14+/-0.02 vs. 0.07+/-0.01 ng of Cr/mg creatinine). The urinary losses of Cr were inversely correlated with plasma estradiol. Median value of urinary Cr was higher in postmenopausal women exhibiting endogenous estradiol levels below 250 pmol/l, whereas women with estradiol levels >250 pmol/l, exhibited lower Cr values. Plasma fructosamine, total and LDL cholesterol and TC/HDL ratio, which are all decreased by improved Cr nutrition, were also improved in the women receiving HRT. There were also nonsignificant decreasing trends in DHEA-sulfate (P<0.06) and cortisol (0.07). CONCLUSIONS: Chromium status, based upon blood and urinary analyses, and glucose, insulin and lipid variables were improved in postmenopausal women receiving HRT. Additional studies are needed to determine if improved Cr status due to supplemental Cr can elicit effects consistent with those of hormone replacement therapy.

Administration, Oral↗

Leptin production in pre- and postmenopausal women.

OBJECTIVES: To investigate the differences in leptin production between pre- and postmenopausal women. METHODS: Subjects were 75 pre- and 75 postmenopausal women. Age, height, weight, and body mass index (BMI, wt/ht(2)) were recorded. Serum leptin levels were measured by RIA. Total body fat mass and percentage of body fat mass were measured by whole-body scanning with dual-energy X-ray absorptiometry. Serum leptin levels, the ratio of serum leptin levels to total body fat mass (leptin-fat mass ratio), baseline characteristics, and anthropometric variables were compared between the two groups. In all subjects (n=150), relationship of serum leptin levels with menopausal status (pre- and postmenopause) was investigated by univariate and multiple regression analysis. RESULTS: Serum leptin levels in premenopausal women 8.4+/-4.8 ng/ml, which did not differ from that in postmenopausal women (9.2+/-7.1 ng/ml). Total body fat mass, percentage of body fat mass, and BMI did not differ between the two groups. Leptin-fat mass ratio in premenopausal women was 0.43+/-0.17 ng/ml/kg, which did not differ from that in postmenopausal women (0.44+/-0.24 ng/ml/kg). On both univariate and multiple regression analysis, serum leptin levels were not correlated with menopausal status. CONCLUSIONS: Menopausal status does not have a significant impact on leptin production.

Adult↗

Difference in the effects of body composition on bone mineral density between pre- and postmenopausal women.

OBJECTIVE: This study was to investigate whether the effect of lean and fat mass component on bone mineral density (BMD) differs between pre- and postmenopausal women. MATERIALS AND METHODS: Subjects were 360 pre- and 193 postmenopausal Japanese women with right side dominance. Age, height, and years since menopause (YSM, in postmenopausal women) were recorded. Body fat and lean body mass were measured by whole body scanning with dual-energy X-ray absorptiometry (DEXA). BMD of the vertical axis (L2-4 of the lumbar spine, pelvis, bilateral legs, and total body) and horizontal axis (arms) were also measured by DEXA. RESULTS: In premenopausal women, lean body mass was independently correlated with BMD of the left arm (partial correlation coefficient = 0.417), right arm (0.430), L2-4 (0.285), pelvis (0.276), left leg (0.403), right leg (0.412), and total body (0.377) (P < 0.001). However, body fat mass was not correlated with several BMD sites except for pelvis BMD (0.187, P < 0.01). In postmenopausal women, body fat mass was independently correlated with BMD of the left arm (0.248, P < 0.01), L2-4 (0.188, P < 0.05), pelvis (0.263, P < 0.01), left leg (0.228, P < 0.01), right leg (0.319, P < 0.001), and total body (0.188, P < 0.01)). However, lean body mass was correlated with BMD in only three segmental regions including left arm (0.175), right arm (0.217), and left leg (0.210; P < 0.05). CONCLUSION: Lean body mass is a significant determinant of BMD in premenopausal women, while body fat mass is a significant determinant in postmenopausal women.

Absorptiometry, Photon↗

Effects of estradiol alone or in combination with cyproterone acetate on carotid artery pulsatility index in postmenopausal women.

OBJECTIVES: The incidence of cardiovascular disease (CVD) increases dramatically with the loss of ovarian function. Observational studies indicate that the risk of CVD may be reduced by up to 50% in postmenopausal women who take estrogen replacement therapy. Estrogen therapy reduces internal carotid artery pulsatility index (PI). The improvement in carotid PI following HRT has been proposed as a marker of the cardioprotective effect of estrogen therapy. Cyclical progesterone addition to ERT partially antagonizes the reduction on the carotid artery PI. As progesterone, androgens has been shown to decreases arterial vasodilatation and carotid PI. To our knowledge no information is available regarding the effect of CPA addition on the carotid artery PI in women taking estrogen replacement therapy. METHODS: We recruited a total of 30 women in postmenopause for at least 12 months and were in good health. Fifteen women were postmenopausal following surgical bilateral oophorectomy for benign condition. Fifteen postmenopausal women received estradiol valerate for 21 days and CPA (1 mg) for 10 days for 3 months (Group E/CPA). Ovarectomized women (n=15) received estradiol hemihydrate (2 mg) for 3 months (Group E). The main factor investigated was PI, an indicator of impedence to blood flow down stream. Doppler US were performed before the start and at the end of the therapy. RESULTS: The mean reductions respect to basal values were 11.5% in women treated with E and 10.8% in women treated with E/CPA. No significant difference was found between treatment values. CONCLUSIONS: The results of the present study demonstrate that cyproterone acetate addition to E do non-antagonize the effect of estrogen on carotid artery PI. The present study demonstrate that both estradiol hemihydrate and estradiol valerate plus cyproterone acetate lead to similar improvement in carotid artery; through this mechanism both treatments could potentially reduce the incidence of cerebrovascular disease in postmenopausal women.

Cardiovascular Diseases↗

The effect of body composition on bone density in pre- and postmenopausal women.

OBJECTIVES: To investigate the relative contribution of body composition (lean and fat) to bone mineral density (BMD), 196 premenopausal and 128 postmenopausal Japanese women were enrolled. METHODS: Total fat mass, total lean mass, lumbar BMD (L2-L4), and total body BMD were measured by dual-energy X-ray absorptiometry (DEXA, Hologic QDR 2000, MA. USA). Physical characteristics were also recorded for each subject. Correlation between BMD and variables were calculated for each of the two groups in single and stepwise regression analyses. RESULTS: Total lean mass was significantly higher in premenopausal women than postmenopausal women (P < 0.0001), while body weight, body mass index, and total fat mass were not different between the two groups. In stepwise regression analysis, total lean mass was the most powerful determinant of lumbar BMD and total body BMD in premenopausal women. In postmenopausal women, total fat mass was the most significant determinant of lumbar BMD, while total lean mass was the most significant determinant of total body BMD. CONCLUSIONS: These findings suggest that there is a difference between pre- and postmenopausal women in the relative contribution of lean and fat mass. Total lean mass is the most significant determinant of BMD in premenopausal women. On the other hand, total fat mass may have some advantages in maintaining BMD in postmenopausal women.

Adipose Tissue↗

The effect of tibolone on cardiac flow in postmenopausal women with non-insulin dependent diabetes mellitus.

OBJECTIVE: Postmenopausal women with non-insulin dependent diabetes (NIDDM) are frequently obese, hypertensive and hyperlipidaemic and hence at particular risk of coronary heart disease (CHD). They might therefore benefit from menopausal therapy. In view of the fact that oestrogen replacement increases cardiac flow but not limb flow whilst tibolone dilates forearm flow in healthy postmenopausal women, a study was undertaken to evaluate the effects of tibolone on cardiac flow in postmenopausal women with NIDDM. DESIGN: A prospective 12 months before/after intervention study. PATIENTS: 15 postmenopausal women (mean age 58.36 +/- 1.25 years; mean duration of menopause 115.20 +/- 13.97 months; mean BMI: 26.22 +/- 1.02) with NIDDM (mean duration of diabetes 106.07 +/- 15.66 months). MEASUREMENTS: Cardiac flow was measured every 6 months for 1 year by pulsed Doppler echocardiography. The parameters assessed were: stroke volume (SV), cardiac output (CO), ejection fraction (EF), pre-ejection time (PEP), ejection time (ET), peak systolic flow velocity (PFV), acceleration time (AT), flow velocity integral (FVI), mean acceleration (MA), early diastolic filling time (Ei), atrial filling time interval (Ai), peak velocity of the early diastolic filling (E) and peak velocity of the early atrial filling (A). Blood pressure was also recorded during Doppler echocardiography. RESULTS: Stroke volume, cardiac output and ejection fraction increased significantly after 6 months. There was also a significant increase in peak flow velocity (PFV), flow velocity integral (FVI) and mean acceleration (MA) together with a significant increase in early diastolic filling time (Ei) and peak velocity of the early diastolic filling (E). Blood pressure was unchanged throughout the 12-month study period. CONCLUSION: The significant increase in stroke volume, cardiac output and flow velocity over the aortic valve parallel the effects of oestrogens in healthy postmenopausal women. The fact that tibolone improved left ventricular relaxation suggests the drug might help prevent or at least defer the development of cardiac dysfunction in diabetic women.

Anabolic Agents↗

17Beta-estradiol delivered by three different matrix patches 50 microg/day: a three way cross-over study in 21 postmenopausal women.

The aim of this study was to investigate the systemic bioavailability and plasma profiles of 17beta-estradiol (E2) after the application of three matrix patches for the transdermal delivery of E2: Menorest, Tradelia, and Estraderm MX claiming to deliver a dosage of 50 microg E2/day. All three patches were each worn randomly by 21 postmenopausal women volunteers over a 4-day period (i.e. 96 h). Each of the three treatment periods were separated by an at least 7 day wash out period according to a randomized, 3-way crossover design. Blood samples were taken from the antecubital vein before and 3, 6, 9, 12, 24, 28, 33, 48, 57, 72, 81, and 96 h after application. E2 plasma values were determined by a specific direct radioimmunoassay method. The following pharmacokinetic parameters were evaluated: AUC0-96h, Cmax, Tmax, Cmin, C(average). The time to reach the maximal E2 value of 32 h was the only pharmacokinetic parameter which was identical for all three patches. Menorest produced the highest E2 bioavailability judged by the AUC0-96h = 3967.8 +/- 1651.8 pg/ml, C(average) = 41.3 +/- 21.3 pg/ml, Cmin = 36.8 +/- 8.6 pg/ml. Tradelia showed statistically not significantly smaller C(average) = 38.9 +/- 17.0 pg/ml, AUC0-96h = 3737.9 +/- 1637.6 pg/ml x per h, and Cmin = 33.8 +/- 26.7 than Menorest. Estraderm MX showed lowest E2 plasma profiles Cmax = 38.9 +/- 25.1 pg/ml, C(average) = 33.2 +/- 17.1 pg/ml, AUC0-96 = 3192.1 +/- 1646.0 pg/ml per x h. Menorest showed the smallest fluctuation over the entire test period, similar to Estraderm MX, while Tradelia showed the highest E2-fluctuation (P < 0.01): Tradelia exhibited the highest Cmax = 48.0 +/- 20.3 pg/ml. When E2 baseline levels, prior to patch application are subtracted individually from the produced E2 plasma level, Estraderm MX is not bioequivalent to Menorest (P < 0.05). A circadian curve pattern of the E2 plasma level was observed for all patches: in the evening higher E2 plasma level were always detected compared with the morning, however, less pronounced with Estraderm MX. Individual comparison of AUC0-96h of each patch exhibited a large interindividual variability of 2000-8000 pg/ml per h for all three patches but relatively small individual variability: women with high E2 bioavailability (high responders) maintained high bioavailability in all applied patches, women identified as low and medium responders remained the same regardless of the applied patch. Menorest produced in 2/3 of all postmenopausal women with the highest E2 bioavailability (AUC0-96h), Tradelia was found in less than 1/3 (28.6%), and Estraderm MX in only one postmenopausal woman. Menorest only produced the highest reduction in postmenopausal symptoms together with Tradelia. Estraderm MX produced a smaller reduction in postmenopausal symptoms compared to Menorest and Tradelia. The observed side-effects were approximately equal in all three patches, with a maximum value after 72 h. It can be concluded that the three patches for the transdermal delivery of E2 claiming to deliver 50 microg E2/day differed from each other in their pharmacokinetic performance, although statistically not significant: Menorest exhibited the highest C(average), AUC and Cmin, and the lowest fluctuation, followed by Tradelia and Estraderm MX.

Administration, Cutaneous↗

Short-term effects of transdermal estrogen replacement therapy on coronary vascular reactivity in postmenopausal women with angina pectoris and normal results on coronary angiograms.

OBJECTIVES: This study sought to analyze the effect of short-term transdermal estradiol treatment on in vivo coronary endothelial function in postmenopausal women with angina and normal results on coronary arteriograms. BACKGROUND: The incidence of coronary heart disease increases in women after menopause. Estrogen replacement therapy has been associated with a global reduction in cardiovascular disease incidence and mortality. In addition, coronary endothelial dysfunction has been demonstrated in a group of postmenopausal women. It has been shown that intravenous or intracoronary estrogens improve endothelial function in postmenopausal women with coronary atherosclerosis. However, the efficacy of this treatment is unknown in patients with angina and normal coronary arteries. METHODS: Endothelium-dependent coronary reactivity was analyzed in 15 postmenopausal women with angina and normal coronary arteries at baseline and after 24 h of estradiol transdermal administration (100 microg). RESULTS: Estradiol concentration increased from 22 +/- 8 pg/ml (mean +/- SEM) at baseline to 76 +/- 13 pg/ml (p < 0.01) at 24 h. At baseline, acetylcholine induced vasoconstriction, with a mean diameter reduction of -23 +/- 6% (p = 0.002). After estrogen treatment, there was no vasoconstriction with acetylcholine, with a mean diameter change of 0 +/- 4%, significantly different from the pretreatment diameter reduction observed (p = 0.003). Similarly, estimated coronary blood flow significantly increased in response to acetylcholine after estrogen treatment, with a mean change of 50 +/- 30% compared with 5 +/- 24% before estradiol administration (p = 0.04). CONCLUSIONS: Early after transdermal estrogen administration, endothelium-dependent coronary vasomotion is improved in postmenopausal women with angina and normal coronary arteries.

Aged↗

Modulation of circulating cellular adhesion molecules in postmenopausal women with coronary artery disease.

OBJECTIVES: The present study examined the association of estrogen (E2) and the inflammatory response of endothelium in coronary artery disease (CAD) by measuring circulating cellular adhesion molecules (cCAMs) in subjects with atherosclerosis. BACKGROUND: Atherosclerotic plaque demonstrates features similar to inflammation. Endothelial cell activation by inflammatory cytokines induces expression of cellular adhesion molecules (CAMs), thereby perhaps augmenting leukocyte adhesion and recruitment and subsequent development of atherosclerosis. The incidence of CAD is lower in women; this may be due to the cardioprotective effects of E2. METHODS: Consecutive eligible subjects with CAD admitted for cardiac catheterization were studied. The groups evaluated were men, postmenopausal women receiving E2 replacement therapy (ERT), postmenopausal women not receiving ERT and premenopausal women. Control groups included men and women without CAD. Preprocedural blood samples were drawn from all groups. Measurements of cCAMs, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 were performed by enzyme-linked immunoabsorbant assay. E2 levels were assessed by radioimmunoassay. RESULTS: We observed a statistically significant increase in all cCAMs in men with CAD and postmenopausal women with CAD not receiving ERT compared with postmenopausal women with CAD receiving ERT. Premenopausal women with CAD and postmenopausal women with CAD receiving ERT had a significant increase in VCAM-1 alone compared with the female control group. CONCLUSIONS: A possible mechanism by which E2 exerts one of its cardioprotective effects is by limiting the inflammatory response to injury by modulating the expression of CAMs from the endothelium.

Adult↗

Hormone replacement therapy in postmenopausal women protects against smoking-induced changes in vascular structure and function.

OBJECTIVES: The purpose of this study was to investigate the role of hormone replacement therapy (HRT) in postmenopausal women who smoke. BACKGROUND: Hormone replacement therapy appears to afford cardiovascular protection in postmenopausal women; however, in high risk individuals, specifically smokers, this has not been adequately studied. This question was addressed in a cross-sectional study of arterial structure, function and plasma lipids in postmenopausal smokers and nonsmokers. METHODS: Vascular ultrasound was performed in two age-matched groups of postmenopausal women, 70 on HRT (35 smokers) and 70 control subjects not on HRT (35 smokers). Indexes of arterial structure (carotid intima-media thickness [IMT]) and vascular function (systemic arterial compliance [SAC]) and lipid profiles were measured. RESULTS: Participant characteristics were similar in the two groups. Smokers on HRT, compared with smoking control subjects, had lower cholesterol (6.0+/-0.2 vs. 6.8+/-0.3 mmol/liter, p = 0.03) and more favorable mean values for IMT (0.64+/-0.02 vs. 0.74+/-0.03 mm, p = 0.007) and SAC (0.41+/-0.03 vs. 0.32+/-0.03 U/mm Hg, p = 0.03). Nonsmokers on HRT compared with nonsmoking control subjects had lower total cholesterol (5.7+/-0.2 vs. 6.5+/-0.2 mmol/liter, p = 0.02) and low density lipoprotein cholesterol (3.4+/-0.2 vs. 4.4+/-0.3 mmol/liter, p = 0.01). Mean IMT and SAC values in nonsmokers on HRT and control subjects were not significantly different. Multiple regression demonstrated significant correlation between HRT status and both IMT and SAC, in smokers and in those with increased cholesterol. In nonsmokers and those with lower cholesterol, HRT status was not significantly correlated with vascular parameters. CONCLUSIONS: In postmenopausal women who smoke there may be a beneficial effect of long-term estrogen therapy on indexes of arterial structure and function as surrogate markers of cardiovascular disease. Long-term controlled studies are needed to confirm these findings.

Arteries↗

Effects of oral L-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women.

OBJECTIVES: We examined whether oral administration of L-arginine, the substrate for nitric oxide (NO) synthesis, increases NO bioactivity in healthy postmenopausal women. BACKGROUND: Nitric oxide may protect arteries against atherosclerosis, as suggested by experimental studies in animals. Estrogen therapy, which has been shown to increase NO bioactivity in the vasculature of healthy postmenopausal women, is not acceptable for long-term use by many women. METHODS: In a randomized, double-blind, crossover study, 10 postmenopausal women without additional risk factors for atherosclerosis received L-arginine 9 g or placebo daily for one month, with treatment periods separated by one month. Nitric oxide levels in serum (as an index of endothelial NO release), brachial artery endothelium-dependent dilator responses to hyperemia by ultrasonography (as an index of vascular NO bioactivity) and markers of inflammation in blood that are inhibited by NO in cell culture experiments were measured at the end of each treatment period. RESULTS: L-arginine levels in plasma were increased in all women during L-arginine treatment compared with placebo (136.8 +/- 63.1 vs. 75.2 +/- 16.2 micromol/liter, p = 0.009). However, there was no change in serum nitrogen oxide levels (42.1 +/- 24.5 vs. 39.1 +/- 16.6 micromol/liter, p = 0.61), nor was there an effect of L-arginine on flow-mediated dilation during hyperemia (3.8 +/- 3.0% vs. 4.9 +/- 4.8%, p = 0.53) compared with placebo. Our study had sufficient power (beta = 0.80) to detect a true absolute treatment difference in flow-mediated brachial artery dilation of 1.7% or larger as statistically significant at alpha = 0.05. There was no effect of L-arginine on serum levels of soluble cell adhesion molecules compared with placebo: E-selectin (50.6 +/- 14.8 vs. 52.1 +/- 17.0 ng/ml, p = 0.45), intercellular adhesion molecule-1 (230 +/- 51 vs. 230 +/- 52 ng/ml, p = 0.97) and vascular cell adhesion molecule-1 (456 +/- 62 vs. 469 +/- 91 ng/ml, p = 0.53). CONCLUSIONS: Oral administration of L-arginine may not augment endothelial NO synthesis and release in postmenopausal women and is thus unlikely to be of general benefit to healthy postmenopausal women in protection from the development of atherosclerosis.

Administration, Oral↗

Lack of association of lipoprotein(a) levels with coronary calcium deposits in asymptomatic postmenopausal women.

OBJECTIVES: This study sought to determine the relationship of lipoprotein(a) (Lp(a)) and other cardiac risk factors to coronary atherosclerosis as measured by calcification of coronary arteries in asymptomatic postmenopausal women. BACKGROUND: Lipoprotein(a) is considered a risk factor for coronary heart disease. Coronary calcium deposition is believed to be a useful noninvasive marker of coronary atherosclerosis in women. However, to our knowledge, there are no reports of the relationship of Lp(a) to coronary calcium in postmenopausal women. METHODS: In 178 asymptomatic postmenopausal women (64 +/- 8 years), we measured Lp(a) and other cardiac risk factors: age, hypertension, diabetes, low-density lipoprotein cholesterol, smoking status, body mass index, physical activity level and duration of hormone replacement therapy. Electron-beam computed tomography was done to measure coronary calcium (calcium score). We analyzed the relationship between calcium score and cardiac risk factors using multivariate analysis. RESULTS: Although calcium score correlated with traditional risk factors of age, diabetes, hypertension and smoking, it did not correlate with Lp(a) in the asymptomatic postmenopausal women. Similar multivariate analyses were done in the subjects age >60 years and in the subjects with significant coronary calcium deposit (calcium score > or =50). These analyses also have failed to show an association of levels of Lp(a) with coronary calcium deposits. CONCLUSIONS: We conclude that in asymptomatic postmenopausal women, Lp(a) levels do not correlate with coronary atherosclerosis as measured by coronary calcium deposits.

Adult↗

Effect of combination hormone replacement therapy on ambulatory blood pressure and arterial stiffness in diabetic postmenopausal women.

BACKGROUND: Diabetes mellitus negates the premenopausal gender benefit with respect to coronary artery disease. Whether hormone replacement therapy (HRT) offers any cardiovascular advantage to diabetic postmenopausal women is not known. Diabetic subjects have increased vascular load and abnormal 24-h blood pressure (BP) profiles. Hormone replacement therapy has been shown to improve indexes of arterial load in nondiabetic postmenopausal women as well as to restore circadian variation in BP. This aim of this study, therefore, was to determine prospectively whether HRT improved arterial stiffness and 24-h ambulatory BP profile in diabetic postmenopausal women. METHODS: Twelve diabetic postmenopausal women were studied. Six subjects were also hypertensive. Vascular load was characterized by carotid arterial pulse waveform analysis to calculate central augmentation index. All subjects also underwent 24-h BP monitoring. Subjects were studied before commencement of HRT and were then randomized to two groups. The first group was observed for 6 months and then given 2 months of estrogen alone, followed by 4 months of combination estrogen with progestin. The second group received the HRT regimen first, then were restudied after 6 months off HRT. RESULTS: The HRT did not affect either clinic or ambulatory BP. There were no changes in indexes of vascular load or pulse pressure, an indirect measure of arterial stiffness. There was a low rate of circadian variation in 24-h BP at baseline (55%), which was unaltered by HRT. CONCLUSIONS: The HRT was well tolerated. Despite evidence for a beneficial effect of HRT on indexes of arterial load and ambulatory BP previously reported in normal subjects, we found no change in this cohort of diabetic postmenopausal women.

Aged↗

Usefulness of lumbar AP spine DXA for measuring the percentage of perilumbar regional fat and predicting visceral fat in obese postmenopausal women.

We investigated whether measurement of the perilumbar regional fat amount by lumbar spine DXA is as good a predictor of visceral fat in obese postmenopausal women. Twenty-two obese (BMI 30-383 kg/m(2)) and 18 nonobese (BMI 20.1-24.7 kg/m(2)) postmenopausal women with similar age were recruited. Lumbar AP spine DXA for measuring the percentage of perilumbar regional fat and CT scanning for estimation of the abdominal visceral fat areas were performed. In obese subjects, visceral fat areas as measured by CT were significantly correlated with BMI, waist circumference, WHR, and DXA-measured perilumbar regional fat percentage. In nonobese subjects, visceral fat areas measured with CT were correlated with BMI, waist circumference, WHR, and DXA-measured perilumbar regional fat percentage. The results of multiple regression analysis were that the perilumbar regional fat percent by DXA was the best predictor of visceral fat amount in obese postmenopausal women (R(2) = 0.750) and BMI predicted visceral fat amount in nonobese postmenopausal women (R(2) = 0.343). This study suggests that lumbar regional fat percentage, as measured by DXA, is a better predictor of abdominal visceral fat amount than waist circumference, WHR, or BMI in obese postmenopausal women.

Abdomen↗

Independent predictors of all osteoporosis-related fractures in healthy postmenopausal women: the OFELY study.

Several epidemiological studies have identified clinical factors that predict the risk of hip fractures in elderly women independently of the level of bone mineral density (BMD), such as low body weight, history of fractures, and clinical risk factors for falls. Their relevance in predicting all fragility fractures in all postmenopausal women, including younger ones, is unknown. The objective of this study was to identify independent predictors of all osteoporosis-related fractures in healthy postmenopausal women. We prospectively followed for 5.3 +/- 1.1 years a cohort of 672 healthy postmenopausal women (mean age 59.1 +/- 9.8 years). Information on social and professional conditions, demographic data, current and past medical history, fracture history, medication use, alcohol consumption, caffeine consumption, daily calcium intake, cigarette smoking, family history of fracture, and past and recent physical activity was obtained. Anthropometric and total hip bone mineral density measurements were made. Incident falls and fractures were ascertained every year. We observed 81 osteoporotic fractures (annual incidence, 21 per 1000 women/year). The final model consisted of seven independent predictors of incident osteoporotic fractures: age > or = 65 years, odds ratio estimate (OR), 1.90 [95% confidence interval (CI) 1.04-3.46], past falls, OR, 1.76 (CI 1.00-3.09), total hip bone mineral density (BMD) < or = 0.736 g/cm(2), OR, 3.15 (CI 1.75-5.66), left grip strength < or = 0.60 bar, OR, 2.05 (CI 1.15-3.64), maternal history of fracture, OR, 1.77 (CI 1.01-3.09), low physical activity, OR, 2.08 (CI 1.17-3.69), and personal history of fragility fracture, OR, 3.33 (CI 1.75-5.66). In contrast, body weight, weight loss, height loss, smoking, neuromuscular coordination assessed by three tests, and hormone replacement therapy were not independent predictors of all fragility fractures after adjustment for all variables. We found that some--but not all--previously reported clinical risk factors for skeletal fragility predicted all fragility fractures independently of BMD in healthy postmenopausal women, although they differed somewhat from those predicting specifically hip fractures in elderly women. These risk factors appear to reflect quality of bone structure (previous fragility fracture), lifestyle habits (physical activity), muscle function and health status (grip strength), heredity (maternal history of fracture), falls, and aging. Measurements of these variables should be included in the clinical assessment of the risk of osteoporotic fractures in postmenopausal women.

Aged↗

Cross-sectional and longitudinal assessment of pre- and postmenopausal bone loss with a portable forearm X-ray device: the Ofely study.

The aim of our study was to describe cross-sectional and longitudinal bone mineral decrease in pre-, peri-, and postmenopausal healthy women using a monoenergy X-ray densitometer specifically designed for forearm assessement. Measurements were performed on the most distal part of the radius (ultradistal, 55% of trabecular bone and 45% of trabecular bone), and on the distal part (distal, 13% of trabecular bone and 87% of cortical bone). A specific trabecular-rich region of interest (nROI) comprising two trapezoids regions of interest located proximally to the endplates of the radius and ulna was also investigated. From a large prospective study (OFELY study), 455 women were measured once a year for 2 years (three measurements). The proportion of postmenopausal women classified as having osteoporosis (i.e., a T score <-2.5) was 33% for the distal region, 44% for the ultradistal region, and 45% for the nROI. No significant bone mineral decrease was found over the 2-year period in premenopausal women (n = 138). In perimenopausal (n = 48) women, a bone loss of 1% was found at the distal site. In the 269 postmenopausal women, a significant decrease was observed at all sites, ranging from 2.14% for the nROI to 2.68% for the ultradistal part. Bone loss was greater in the first 5 years after menopause in trabecular sites and decreased thereafter. For the distal site, bone loss remained stable during the postmenopausal period. We conclude that this small and portable forearm densitometer is suitable for the diagnosis of osteoporosis, and provides information on the rate of bone loss in peri- and postmenopausal women in trabecular and cortical compartments of bone.

Absorptiometry, Photon↗

Effect of postmenopausal hormone replacement therapy on lipoprotein and homocysteine levels in Chinese women.

Epidemiological studies have revealed that postmenopausal estrogen replacement therapy results in a marked reduction in the risk for cardiovascular diseases. In the present study, we evaluated plasma lipoprotein profile as well as homocysteine levels in 145 postmenopausal and premenopausal Chinese women living in Hong Kong. We also investigated the effect of hormone-replacement therapy (HRT) with estrogen or estrogen combined with progestin on plasma lipoprotein profile and homocysteine concentrations in those individuals. Postmenopausal women displayed significantly higher plasma levels of total cholesterol, LDL-cholesterol and apoB as well as higher plasma homocysteine levels than that of premenopausal women. HRT with either estrogen (17beta-estradiol or conjugated equine estrogen) alone or estrogen combined with progestin for 3.5-4.5 years significantly improved the lipoprotein profile in postmenopausal women by decreasing the levels of total cholesterol (12-20% reduction), LDL-cholesterol (26-29% reduction) and apoB (21-25% reduction). In women treated with 17beta-estradiol or conjugated equine estrogens their plasma levels of apoAl were significantly elevated (18% elevation) as compared to non-users. HRT also reduced plasma concentrations of homocysteine (13-15% reduction). In conclusion, we found that long-term HRT was associated with improvement in plasma lipoprotein profile and a reduction in homocysteine concentration in postmenopausal women. These results support the notion that the improvement of lipoprotein profile and a reduction in homocysteine concentration may contribute to the beneficial effect of HRT on cardiovascular risk.

Adult↗