***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Physiological responses that involve adrenergic mechanisms , such as stress-induced changes in cardiovascular indices , were reported to fluctuate along the menstrual cycle . Metastatic development following surgery was also reported to vary according to the menstrual phase during which a primary breast tumour was removed . Natural killer ( NK ) cells are believed to play an important role in controlling metastases . Our recent studies in rats demonstrated that adrenergic suppression of NK activity and of resistance to metastasis is more profound during oestrous phases characterized by high levels of oestradiol . In the current study in humans , we examined the in vitro impact of a β-adrenergic agonist , metaproterenol ( MP ) , on NK activity , comparing blood drawn from ( a ) women tested at 3–4 different phases of their menstrual cycle ( n = 10 ) , ( b ) women using oral contraceptives ( OC ) ( n = 10 ) , and ( c ) men ( n = 7 ) .  NK activity in each blood sample was assessed in the presence of 5 different concentrations of MP ( 10–8 M to 10–6 M ) , and in its absence ( baseline ) . The results indicated marked group differences in the magnitude of NK suppression by MP : EC50was 2.6-fold lower in the luteal phase compared to the follicular phase , and 1.8-fold lower in OC users compared to men , who were least susceptible to the effects of MP . No significant group differences or menstrual effects in baseline levels of NK activity were evident . These findings provide the first empirical evidence for menstrual regulation of adrenergic impact on cellular immune competence . Relevance of these findings to the relation between the timing of breast cancer excision within the menstrual cycle and survival rates is discussed . © 2000 Cancer Research Campaign Background —The increase in C-reactive protein ( CRP ) during oral conjugated equine estrogen ( CEE ) may explain the initial excess of cardiovascular disease observed in clinical studies . Because the effect of transdermal estradiol ( E2 ) on CRP is unclear , we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a r and omized 2 × 2 retinoid-placebo trial . Methods and Results —A total of 189 postmenopausal women were r and omized to 50 & mgr;g/d  transdermal E2 and 100 mg BID of the retinoid fenretinide ( n=45 ) , 50 & mgr;g/d transdermal E2 and placebo ( n=49 ) , 0.625 mg/d oral CEE and 100 mg BID fenretinide ( n=46 ) , or 0.625 mg/d oral CEE and placebo ( n=49 ) for 1 year . Sequential medroxyprogesterone acetate was added in each group . Relative to baseline , CRP increased by 10 % ( 95 % CI −9 % to 33 % ) and by 48 % ( 95 % CI 22 % to 78 % ) after 6 months of transdermal E2 and oral CEE , respectively . The corresponding figures at 12 months were 3 % ( 95 % CI −14 % to 23 % ) for transdermal E2 and 64 % ( 95 % CI 38 % to 96 % ) for oral CEE . Fenretinide did not change CRP levels at 6 and 12 months relative to placebo . Relative to oral CEE , the mean change in CRP after 12 months of transdermal E2 was −48 % ( 95 % CI −85 % to −7 % , P = 0.012 ) , whereas fenretinide was associated with a mean change of −1 % ( 95 % CI −34 % to 40 % , P = 0.79 ) compared with placebo . Conclusions —In contrast to oral CEE , transdermal E2 does not elevate CRP levels up to 12 months of treatment . The implication s for early risk of coronary heart disease require further studies Objective —We observed that estrogen did not show cardioprotective benefits in type 2 diabetic postmenopausal women . We hypothesized that hypertensive and /or overweight women may be less likely to realize cardiovascular benefits from estrogen . Methods and Results —We administered micronized progesterone ( MP ) 100 mg or medroxyprogesterone acetate ( MPA ) 2.5 mg with conjugated equine estrogen ( CEE ) 0.625 mg daily during 2 months to 35 hypertensive and /or overweight postmenopausal women with a r and omized , double-blind , crossover design . With significant changes of lipoproteins , CEE+MP or MPA significantly improved flow-mediated dilation and reduced plasma E-selectin , intercellular adhesion molecule type-1 , monocyte chemoattractant protein-1 , and tumor necrosis factor-&agr ; levels ( P < 0.001 , P < 0.001 , P = 0.021 , P < 0.001 , and P < 0.001 by ANOVA , respectively ) , but not C-reactive protein and fibrinogen levels . Of note , there were no significant differences between each therapy regarding these effects . However , the magnitude of improvement of flow-mediated dilation in these women was less than in healthy postmenopausal women and more than in diabetic postmenopausal women reported by our previous studies . The effects of CEE+MP or  MPA on inflammatory markers were comparable to healthy postmenopausal women , but not comparable to diabetic postmenopausal women . Conclusions —Estrogen combined with synthetic progestin significantly improved flow-mediated brachial artery dilator response and reduced inflammation markers in hypertensive and /or overweight women , comparable to estrogen combined with natural progesterone Background —HMG-CoA reductase inhibitor ( statin ) therapy reduces cardiovascular risk , mechanisms of which may include diminished arterial inflammation , as suggested by reduction in levels of C-reactive protein ( CRP ) . Because oral estrogens increase CRP in postmenopausal women , with potential inflammatory and thrombotic consequences that could compromise any benefit to cardiovascular risk , we determined whether the coadministration of a statin might modify the estrogenic effect on CRP . Methods and Results —In a double-blind , 3-period crossover study , 28 postmenopausal women ( average LDL cholesterol 163±36 mg/dL ) were r and omly assigned to daily conjugated equine estrogens ( CEEs ) 0.625 mg , simvastatin 10 mg , or their combination for 6 weeks , with each treatment period separated by 6 weeks . CEEs increased median CRP levels from 0.27 to 0.46 mg/dL , simvastatin  decreased CRP from 0.29 to 0.28 mg/dL , and the therapies combined increased CRP from 0.28 to 0.36 mg/dL ( all P ≤0.02 versus respective baseline values ) . Post hoc testing showed that the 29 % increase in CRP on the combination of CEEs with simvastatin was significantly less than the 70 % increase in CRP on CEEs alone ( P < 0.05 ) . The effect of combination therapy on CRP levels did not correlate with baseline CRP or with baseline or treatment-induced changes in levels of interleukin-6 , lipoproteins , or flow-mediated dilation of the brachial artery as a measure of nitric oxide bioactivity . Conclusions —The combination of statin with estrogen may attenuate the potential harmful effects of estrogen therapy in postmenopausal women and maximize any benefit to cardiovascular risk BACKGROUND The immune system may be compromised after menopause because of the effects of aging and diminishing concentrations of estrogen , an immune-modulating hormone . Isoflavones , plant-derived compounds with estrogenic and antioxidant properties , may offer immunologic benefits to women during this stage of life . OBJECTIVE The objective of this study was to evaluate the effects of soy isoflavones , both in soymilk and in supplement form , on markers of immunity and oxidative stress in postmenopausal women . DESIGN Postmenopausal women aged 50 - 65 y ( n = 52 ) enrolled in this 16-wk double-blind , placebo-controlled trial were r and omly assigned to 1 of 3 experimental groups : 1 ) control , 706 mL cow milk/d plus a placebo supplement ; 2 ) soymilk , 71.6 mg isoflavones derived from 706 mL soymilk/d plus a placebo supplement ; and 3 ) supplement , 70 mg isoflavones in a supplement plus 706 mL cow milk/d . Plasma and 24-h urine sample s were obtained at baseline and at 16 wk . Immune variables included lymphocyte subsets , cytokine production , and markers of inflammation and oxidative damage . RESULTS Isoflavone intervention in postmenopausal women result ed in higher ( P < 0.05 ) B cell population s and lower ( P < 0.05 ) plasma concentrations of 8-hydroxy-2-deoxy-guanosine , an oxidative marker of DNA damage . Isoflavone treatment did not significantly influence concentrations of interferon gamma , interleukin 2 , tumor necrosis factor alpha , or C-reactive protein in plasma or of 8-isoprostane in urine . CONCLUSIONS Soymilk and supplemental isoflavones modulate B cell population s and appear to be protective against DNA damage in postmenopausal women Background Synthetic , not natural , progestagen may negate the favorable effects of estrogen . Nonetheless , observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen  and users of estrogen combined with synthetic progestin . Methods and Results In a double-blind study , we r and omly assigned 20 healthy postmenopausal women to micronized progesterone ( MP ) 200 mg or medroxyprogesterone acetate ( MPA ) 10 mg for 10 days with conjugated equine estrogen ( CEE ) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months , followed by crossover to the alternate therapy . CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements ( P = 0.004 by ANOVA ) by a similar degree ( P = 0.863 ) . Both therapies significantly decreased E-selectin , intercellular adhesion molecule (ICAM)-1 , and vascular cell adhesion molecule (VCAM)-1 levels from baseline values ( P < 0.001 , P = 0.048 , and P = 0.016 by ANOVA , respectively ) by a similar degree ( P = 0.977 for ICAM-1 and P = 0.541 for VCAM-1 , respectively ) . CEE+MPA decreased E-selectin levels more than CEE+MP did ( P = 0.040 ) . Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values ( P < 0.005 by ANOVA ) by a similar degree ( P = 0.194 ) . Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values ( P = 0.003 and P < 0.001 by ANOVA , respectively ) by a similar degree ( P = 0.652 for antigen and P = 0.173 for activity ) . Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values ( P < 0.001 by ANOVA ) by a similar degree ( P = 0.533 ) . Conclusions CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation , hemostasis , and fibrinolysis inhibition in healthy postmenopausal women Background —It has been suggested that hormone replacement therapy ( HRT ) in postmenopausal women is associated with an increased inflammatory response that may trigger acute cardiovascular events . This suggestion is mainly based on the finding of elevated C-reactive protein ( CRP ) levels after HRT . The aim of the present study was to evaluate a broad spectrum of vascular inflammation markers in 389 postmenopausal women with increased cardiovascular risk at baseline and after either 6 months of HRT ( 126 women ) or no HRT ( 263 women ) . Methods and Results —Compared with baseline , CRP levels significantly increased after HRT ( 0.9±0.2 versus 1.6±0.4 mg/L , P < 0.01 ) ; on the contrary , soluble intracellular adhesion molecule-1 decreased from 208±57 to 168±37 ng/mL ( P < 0.01 ) after HRT . Similarly , vascular cell adhesion molecule-1 decreased from 298±73 to 258±47 ng/mL ( P < 0.01 ) , plasma E-selectin levels were reduced from 17.8±5.6 to 14.8±3.9 ng/mL ( P < 0.01 ) , interleukin- 
    Output:
    
After menopause , there is an increase in pro-inflammatory serum markers ( IL1 , IL6 , TNF-alpha ) , an increase in response of the immune blood cells to these cytokines , a decrease in CD4 T and B lymphocytes and a decrease in the cytotoxic activity of NK cells .
Additionally , IL-6 is a key factor in bone resorption and also seems to be associated with other diseases more common after menopause such as diabetes , atherosclerosis and cardiovascular disease .
CONCLUSIONS Most of the studies suggested that in addition to age , in postmenopausal women , changes of the immune system have been attributed to estrogen deprivation .
Furthermore , recent studies point out changes in immune response related to use or cessation of hormone replacement at menopause