Effects of hormone replacement therapy on blood coagulation and fibrinolysis in hypertensive and normotensive postmenopausal women

INTRODUCTION: Hypertension and estrogens are both prothrombotic. We investigated the effect of 12-month hormone replacement therapy (HRT) on hemostatic factors in mild to moderate essential hypertensive and normotensive postmenopausal women. MATERIALS AND METHODS: A group of 38 hypertensive and 32 normotensive postmenopausal women received HRT (conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg daily) for 12 months, and 19 hypertensive and 15 normotensive postmenopausal women did not. All hypertensive women had been administered antihypetensive drugs before the start of the study. Hemostatic factors, i.e., fibrogen, antithrombin, protein C activity, plasminogen activator inhibitor-1, D-dimer, and plasminogen, were measured in plasma of all women before, and 6 and 12 months after the start of study. RESULT: The antithrombin levels of the hypertensive and normotensive women who received HRT had decreased at 6 (both P<0.001) and 12 months (P<0.001 and P<0.01) and their D-dimer at 12 months (both P<0.05) and plasminogen levels at 6 (both P<0.001) and 12 months (both P<0.001) has increased, but other hemostatic factors were unchanged. There were no changes in hemostatic factors in either control group. CONCLUSION: HRT for 12 months activated blood coagulation and fibrinolysis in both hypertensive and normotensive postmenopausal women. Administration of CEE plus MPA therapy to hypertensive or normotensive postmenopausal women may be related to the thromboembolic events.     

雌激素对绝经后妇女脑梗死及血脂水平的影响

目的探讨雌激素对绝经后妇女脑梗死及血脂水平的影响。方法 用放射免疫分析法和全自动生化分析仪测定50例绝经后妇女脑梗死患者及24例正常人血清E2、TC、TC、HDLC、LDL-C水平。结果 绝经后老年与非老年组脑梗死患者血清E2和HDLC水平均明显低于对照组,而TC、TC、LDLC水平均明显高于对照组(P<0.05~P<0.01)。上述各指标,以老年组改变为最明显,与非老年组相比有显著性差异(P<0.05)。同时老年组有多灶梗死者也明显多于非老年组(P<0.05)。相关分析,E2与IC、IC、LDLC呈负相关,与HDL-C水平呈正相关。结论 绝经后妇女脑梗死患者血清雌激素水平降低是导致脂代谢紊乱及脑梗死发生的主要危险因素。     

Effects of transdermal and oral oestrogen replacement therapy on C-reactive protein levels in postmenopausal women: a randomised,placebo-controlled trial

To investigate the effect of postmenopausal oral and transdermal hormone therapy on plasma levels of C-reactive protein (CRP), we performed a randomised, double-blind, double-dummy, placebo-controlled, 15-month study. One hundred and fifty-two healthy hysterectomised postmenopausal women received daily either placebo (n = 49), or transdermal 17beta-oestradiol (E(2)) 50 micro g (tE(2) group, n = 33), or oral E(2) 1 mg (oE(2) group, n = 37), or oral E(2) 1 mg combined with gestodene 25 micro g (oE(2) + G group, n = 33) for thirteen 28-day treatment cycles, followed by four cycles placebo for each group. Data were collected at baseline and in cycles 4, 13 and 17. In cycle 13, CRP was significantly increased in the oE(2) group compared to placebo (P = 0.004). The median percentage change from baseline versus placebo was +75% (P <0.001). In cycle 17, significantly lower values were observed in the oE(2) group compared to cycle 13 and to the placebo group (-49%, P <0.001). There were no significant changes versus placebo in the other groups. In conclusion, oral E(2) significantly increased CRP levels. This change was larger than the increase found during oral E(2) + G. Transdermal E(2) did not affect CRP levels.     

Differential effects of oral and transdermal postmenopausal estrogen replacement therapies on C-reactive protein

C-reactive protein (CRP) is one of the main independent predictors of cardiovascular events. Oral post-menopausal estrogen replacement therapy (ERT) increases CRP levels, but the effect of transdermal ERT is not well documented. CRP, interleukine-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were evaluated in a randomised study of 196 healthy postmenopausal women, who were allocated to receive continuous oral estradiol-1beta, (n=63) or transdermal estradiol-1beta, (n=68) both combined with micronised progesterone, or place-bo (n=65). Oral estrogen increased CRP levels compared with both placebo (p=0.010) and transdermal estrogen (p=0.004) at 6 months. There was no significant effect of transdermal estrogen on CRP levels compared with placebo (p=0.997). No significant difference was found in the median changes for IL-6 and TNF-alpha between the three treatment groups. In conclusion, transdermal estrogen has no significant effect on CRP levels at 6 months, but CRP concentrations increased significantly with oral estrogen although no changes in cytokine levels were detected. The clinical relevance of these effects remains to be determined.     

Effects of carbohydrate feeding on blood coagulation,fibrinolysis and platelet adhesiveness — relations to serum lipids and lipoproteins

An isocaloric diet containing 93 calorie % glucose was given for 23 days to 9 obese subjects and 2 normal controls. The influence on blood coagulation, fibrinolysis and platelet function as well as serum lipids and lipoproteins were: Factor II-VII-X activity, fibrinogen dn plasminogen decreased while factor V and factor VIII, antithrombin III, a₁ antitrypsin and α₂ macroglobulin, did not change. Recalcification time of platelet-rich and platelet-poor plasma, Russel viper venom (RVV) clotting time and activated partial thromboplastin time (APTT) were shortened. No one of the factors known to influence on clotting was found to be responsible for the shortening of the clotting times. Platelet adhesiveness decreased unexpectedly. Fibrinolytic activity in plasma and in euglobulin before and after stasis of the arm did not change sifnificantly. Serum cholesterol, low density lipoproteins (LDL) and high density lipoproteins (HDL) decreased while serum triglycerides and very low density lipoproteins (VLDL) increased - the latter preferentially in the obese group with large fat cells. The reduction in HDL caused by the diet was correlated to the decrease in factor II-VII-X and fibrinogen. A strong correlation was found between LDL and platelet adhesiveness and a causal relationship may exist. According to conventional ideas the shortening of clotting times should tend to increase and the lowering of platelet adhesiveness to decrease the tendency to thrombosis. The results of the present work demonstrate the danger in drawing conclusions from studying only one factor in the complicated scheme of hemostasis.     

Effects of long-term estrogen replacement therapy on growth hormone response to pyridostigmine in healthy postmenopausal women

OBJECTIVE: There is growing evidence that estrogen may protect against age-related cognitive decline and reduce the risk of developing Alzheimer's disease (AD) in healthy, postmenopausal women. The underlying biological basis for this is not known but may include preservation of cholinergic systems. Cholinergic dysfunction has been implicated in the aetiology of age-related memory impairment and AD. We studied the effect of prolonged use of estrogen replacement therapy (ERT) on central cholinergic tone in healthy postmenopausal women. METHOD: Growth hormone (GH) responses to oral pyridostigmine (120 mg) were measured over a 3 h period in thirty healthy postmenopausal women, 15 on long-term ERT and 15 ERT na?ve. RESULTS: GH release following pyridostigmine was significantly larger in ERT treated women than in ERT na?ve women. In addition within the ERT treated group there was a significant positive correlation between duration of estrogen treatment and GH response. CONCLUSIONS: Long-term ERT can enhance cholinergic function in postmenopausal women and this may be related to duration of estrogen treatment. Modulation of central cholinergic function may be one mechanism by which long-term ERT could preserve cognitive function in healthy, postmenopausal women.     

Short- and long-term effects of hormone replacement therapy (transdermal estradiol vs oral conjugated equine estrogens, combined with medroxyprogesterone acetate) on blood coagulation factors in postmenopausal women.

We compared the effects on hemostatic variables of transdermal estradiol and oral equine conjugated estrogens (CEE), both combined with medroxyprogesterone acetate, in 40 postmenopausal women, 22 randomly allocated to transdermal estradiol and 18 to CEE. Antithrombin III (AtIII), fibrinogen, factor VII, factor VIII and tissue plasminogen activator before and after venous stasis were measured at the start of therapy and after two and four months in all patients, and after 12 months in a subgroup of 21 patients (12 from the estradiol and nine from the CEE group). In the short-term study (two and four months), analysis of variance did not reveal any significant difference between treatments for any of the hemostatic variables. A significant treatment by time interaction was found only for fibrinogen levels: at two months they were significantly higher in the estradiol group. In the long-term study (12 months), a significant decrease in AtIII and a significant increase in factor VIII were observed in both groups, without differences between treatments. The clinical relevance of the observed changes is doubtful, but nevertheless they should be considered in a more extensive evaluation of the potential cardiovascular risk and benefits of hormone use.     

Reproductive events modify the effects of estrogen replacement therapy on cognition in healthy postmenopausal women

The question of whether estrogen replacement therapy (ERT) is beneficial to cognitive functioning in postmenopausal women has become controversial in the past several years. Early studies suggested that ERT improved cognitive functioning and decreased the risk of Alzheimer's disease, but recent studies have failed to find any benefit. However, studies have varied in terms of the age of participants, the estrogen preparation used, whether progesterone is administered concurrently, and the study design. The present study used a randomized, placebo-controlled design and a transdermal estrogen preparation composed of 17-beta estradiol. A neuropsychological battery was administered at baseline and after completion of the 10-week trial, and test scores were grouped into four composite scores using psychometric techniques. Baseline to follow-up change was analyzed using multiple regression techniques. Results indicate that while little overall beneficial effect of estrogen was found, years since menopause was significantly related to change in executive functioning in the estrogen but not the placebo group, such that more recently postmenopausal women demonstrated greater positive change than older women. Body mass index, a gross estimate of circulating estrogen, was significantly positively related to change in attentional and psychomotor processes regardless of treatment group, and to a weaker extent, verbal memory, but only in the estrogen-treated group. These results suggest that reproductive events and levels of endogenous estrogen are related to the clinical response to ERT, but larger studies with longer follow-up periods are needed to determine the strength of these effects.     

Depression and lipoprotein lipids in healthy, postmenopausal women; the moderating effects of hormone replacement therapy

OBJECTIVE: Naturally occurring low cholesterol levels have been related to increased depressive symptoms in studies conducted predominantly in men. However, depression is more common among women, may increase during the menopause, and may be impacted by hormone replacement therapy (HRT). We therefore examined the potential interactive relation of depressive symptoms and HRT status to lipoprotein lipids among postmenopausal women. METHODS: Seventy healthy, postmenopausal women (ages 50-70; 36% receiving HRT) completed the Center for Epidemiological Studies Depression Scale and provided two fasting blood samples for assessment of lipoprotein lipids. RESULTS: Following statistical adjustment for age, body mass index (BMI), HRT status, and depressive symptoms, the interaction of depression and HRT explained 16% variance in total cholesterol and 17% variance in low-density lipoprotein cholesterol (Ps<.01). Greater levels of depressive symptoms were associated with lower cholesterol levels only among women who were not taking HRT. CONCLUSION: These findings suggest that HRT may buffer associations between naturally occurring low cholesterol levels and increased symptoms of depression in postmenopausal women.     

Alcohol and estrogen replacement therapy in postmenopausal women. Direct and mediated effects on cognitive component processes

The literature remains contentious regarding the separate and combined effects of moderate drinking and estrogen replacement therapy (ERT) on cognition. In the current study, the authors sought to disentangle the predictive utility of alcohol use, ERT and their interaction on the episodic and semantic memory stores of postmenopausal women. It was predicted that relationships between moderate drinking, ERT and cognition would be attenuated by demographic and health-related factors. Postmenopausal women (n = 298) completed a battery of cognitive tests designed to assess speed and accuracy of episodic and knowledge-based cognitive processing. Potentially confounding variables were categorized and tested as mediators in hierarchical regression analyses. Moderate drinking was a weak predictor of episodic availability prior to removal of potential mediators. ERT use was a significant predictor of episodic and knowledge-based availability; no mediators were identified. Alcohol moderated ERT, as a combined alcohol/ERT variable was shown to be related to cognition. Neither moderate drinking nor ERT use was associated with cognitive speed. These findings suggest that positive relationships between alcohol and cognition are likely mediated by other variables, and should not be regarded as a benefit of drinking. Further, results support ERT as a predictor of knowledge-based and episodic availability, independent of mood stabilization or socioeconomic influences. Finally, alcohol and ERT appear to interact to impact both episodic and knowledge-based performance.     

Pilot study on the effect of estrogen replacement therapy on brain dopamine transporter availability in healthy, postmenopausal women.

OBJECTIVE: Authors investigated the association between estrogen replacement therapy (ERT) and dopamine transporter (DAT) availability in women. METHODS: Thirteen postmenopausal women were administered ERT and underwent neuroimaging, using single-photon emission computed tomography (SPECT) and [99mTc]TRODAT-1, a radioligand that binds DAT. In this 6-week pilot study, subjects underwent SPECT before ERT, after 4 weeks of 0.625 mg/day of conjugated estrogens (CEE), and after an additional 2 weeks of 0.625 mg/day CEE plus 10 mg/day of medroxyprogesterone acetate. Specific uptake values (SUVs) of [99mTc]TRODAT-1 were calculated for the caudate and putamen. RESULTS: When compared with baseline values, [99mTc]TRODAT-1 binding demonstrated a modest, but statistically significant, increase in the left anterior putamen after 4 weeks of CEE. After the 6-week ERT intervention, both the left and right anterior putamen demonstrated an increase in SUVs. CONCLUSION: Short-term administration of ERT in postmenopausal women is associated with a modest increase in DAT in the putamen. These findings may further the understanding of how ERT is associated with improvement in Parkinson's disease and late-onset schizophrenia.     

Effect of acute transdermal estrogen administration on basal, mental stress and cold pressor-induced sympathetic responses in postmenopausal women

Abstract Administration of estrogen has vascular effects through poorly defined mechanisms that may include sympathetic withdrawal. To define the effects of acute estrogen administration on sympathetic responses, nineteen healthy postmenopausal women (age 54±2 years) were studied after application of a placebo or estrogen patch for 36 hours, in random order. A p-value, adjusted for multiple comparisons, of <0.017 was used to determine statistical significance. Heart rate, blood pressure, and norepinephrine spillover were measured at rest, during mental stress (Stroop test), and during a cold pressor test. Estrogen did not attenuate basal or stimulated hemodynamic responses significantly. The increase in mean arterial pressure after the Stroop test (5.9±1.2mm/ Hg on placebo vs 6.1±1.6mm/Hg on estrogen, p=0.9) and after the cold pressor test (12.6±2.4mm/Hg on placebo vs 13.0±2.2 mm/Hg on estrogen, p=0.8) did not differ. Basal, mental stress and cold pressor-stimulated norepinephrine spillover were not significantly affected by short-term estrogen administration. Norepinephrine spillover tended to be higher after estrogen (1296.2±238 ng/min) than placebo (832.5±129 ng/min) (p=0.02) at baseline and after the Stroop test (1881.1±330 ng/min vs 1014.6±249 ng/min) (p=0.02). Acute transdermal estrogen administration did not attenuate norepinephrine spillover or sympathetically mediated hemodynamic responses.     

Effects on coagulation and fibrinolysis of desmopressin in patients undergoing total hip replacement.

Twelve patients undergoing total hip replacement, with regional anaesthesia and with dextran infusion for plasma expansion and thromboprophylaxis, were given the vasopressin analogue desmopressin (DDAVP) or placebo in a randomized, double-blind prospective study. In controls (n = 6) we found a prolongation of the bleeding time, low factor VIII (FVIII) and von Willebrand factor (vWF) and a decrease in antithrombin III to levels known to be at risk for venous thrombosis. Desmopressin shortened postoperative bleeding time, gave an early FVIII/vWF complex increase, prevented antithrombin III from falling to critically low values and appeared to activate the fibrinolytic system, both by tPA increase and PAI-1 decrease. Thus in the controls we found changes in both coagulation and fibrinolysis indicating a haemorrhagic diathesis as well as a risk for thromboembolism. Desmopressin induced factor changes that possibly reduce both risks.     

The effect of the synthetic steroid Org OD14 on fibrinolysis and blood lipids in postmenopausal women

Two groups of postmenopausal women were compared. One group of 13 was given the synthetic steroid Org OD14 to suppress climacteric symptoms and one group of 14 was given placebo. After a 2 week baseline period the subjects received daily for 12 weeks, either 2.5 mg Org OD14 or placebo. There were no significant differences between the groups pre-treatment. Compared with the placebo group, during treatment, the Org OD14 group showed the following significant differences: higher haemoglobin, haematocrit, platelet count, plasminogen, fibrinolytic activity on fibrin plates and antithrombin III and lower fibrinogen. No significant differences between the groups were found in alpha 2 antiplasmin levels, total cholesterol, total triglycerides, bilirubin or transaminase levels but the Org OD14 group had significantly lower levels of HDL cholesterol. With the exception of the haemoglobin and haematocrit levels all of the differences had disappeared by 2 weeks post treatment.     

Reduced expression of endothelial cell markers after long-term transdermal hormone replacement therapy in women with coronary artery disease

The effects of 12 months hormone replacement therapy (HRT) on biochemical markers associated with endothelial function were studied in 98 postmenopausal women with CAD, who were randomized to transdermal HRT or a control group. A significant reduction in the levels of von Willebrand factor in the HRT-group compared to controls was seen after 3 months, maintained after 12 months (p <0.001). Significant reduction in the HRT-group compared to controls was also seen in VCAM-1 after 3 months, sustained after 12 months (p = 0.013 and p = 0.045, respectively), and E-selectin was reduced by about 20% after 3 months on HRT, the reduction being statistically significant after 12 months (p <0.001). Significantly reduced levels of ICAM-1 were also seen after 12 months (p = 0.048). No effects could be observed on tPA-antigen or thrombomodulin. The reduction in procoagulant and proinflammatory markers of endothelial function after long-term transdermal HRT could indicate a beneficial effect on the endothelium and thus a potentially modulating effect on the progression of atherosclerosis in women with CAD.     

The effect of chronic anticonvulsant therapy on serum lipids and lipoproteins in epileptic children

We measured serum lipids and lipoproteins in 33 epileptic children who were treated with phenobarbital, valproate, and carbamazepine. High-density lipoprotein cholesterol (HDL-c) was significantly higher in the epileptic children than in two control groups: healthy nonepileptic children, and epileptic children before starting anticonvulsant therapy. Our findings indicate that anticonvulsant drugs should be added to the list of substances that affect serum HDL-c.