Relationship Between Estrogen, Dehydroepiandrosterone And Atherosis In Premenopausal And Postmenopausal Women

Background:Coronary heart disease(CHD) and stroke are diseases with high morbidity and disability which bring negative impact on the people's health and quality of life.Atherosclerosis(AS) is regarded as the their most common etiological factor.The incidence of cardiovascular disease increases along with the ncreasing risk of the AS.People have been making great effort to explain the mechanism of AS to take effective measures for treatment and prevention of AS.Among the hypothesises of the pathogenesis of AS,the "lipid hypothesizes" and the "cell inflammatory response hypothesizes" are the main hypothesis at present.In the researches about AS,the endothelium,inflammatory factors,lipid are the focus.The age and gender are also the risk factors of AS,besides lipid.The morbidity of CHD in the premenopausal women was much lower than in men with the same age. However,for those women aged over sixty,the morbidity was almost the same as for men.The serum estrogen level may have a relation with this,because the risk factors of CHD could not offer a perfect explanation. Our group previous studies have shown that estrogen interacts with lipid metabolism,which decreases the LDL-C.Estrogen plays a significant role in endothelial protection and prevents endothelial cell apoptosis caused by some kinds of cytokine;estrogen promotes endothelial cell growth.Estrogen is also important in antioxidation,which can scavenge free radicals and prevent lipid peroxidation.All of these showed that estrogen can prevent AS.But the mechanisim is not completely certain at present,which should be paid attention to and further study.One of the steroids hormones,Dehydroepiandrosterone(DHEA),belongs to adrenal androgen and remains as dehydroepiandrosterone sulfate(DHEAS) in the serum.DHEA possesses a higher concentration than all the other steroids hormones in human plasma and is the intermediate product of sex hormone.It can be tranfrormed to estrogen,androgen,progestogen,corticosterone and other hormones in target organs,therefore,it was called multiple "sex hormone buffer".As a precursor of estrogen,DHEA was closely correlated to estrogen level.But how the DHEA effect AS is not certain at present,which should be paid attention to and further study.AS is a systemic artery disease and its development is a long process.AS we know,the carotid artery atherosclerosis takes place with the aorta atherosclerosis roughly at the same time and earlier than coronary atherosclerosis.It's already an accepted fact that the carotid artery atherosclerosis is regarded as independent predictive factor of coronary atherosclerosis.The thickness of intima-media(IMT) measured by B-mode ultrasound is believed to show the development of AS at an early stage.The B-mode ultrasoundgraphy check are economical,convenient, non-invasive,painless than angiography.Furthermore the High Resolution B-mode ultrasoundgraphy check can clearly display the vascular wall lesions and assess directly.It can be used all kind of AS.So in clinical practice,the IMT level was to represent the degree of AS.The IMT≥0.9mm was consided the increase of IMT.Objectives:The IMT was to represent the degree of AS.To investigate the relationship of estrogen,DHEA and AS,between premenopausal and postmenopausal women.To study the mechanism of AS in lipid,antioxidation, endothelium.Methods:The study involved 40 premenopausal and 40 postmenopausal women from the South China(mainly from Guanzhou City) in Nanfang hospital physical examination center.Recruitment took placed from April 2007 to July 2007. They were randomized into two groups.The eligible criteria include:aged 40-60 years old;without major organ dysfunction or chronic diseases;without any history of infection,trauma,NSAID or hormone during the past four weeks;with normal electrocardiogram,chest X-ray,abdomen ultrasound;without electrolyte disturbance. 8ml venous blood was drawned from each women at 8:00 AM on each day of experimentation.The serum was separated from blood sample and stored at -20℃and were subsequently detected a month later.The serum levels of DHEA, superoxide dismutase(SOD),endothelin(ET),antioxidation,malei dialdehyde (MDA),E-selectin were measured by enzyme linked immunosorbent assay(ELISA). Accord to the specification of elisa kit to prepare reagent,the optical density value (OD) was detected by spectrophotometer or enzyme-labelled meter after a sufficient raction.After establishing standard curves by computer,the serum sample concentration was calculated.The levels of serum E2 were measured by electrochemiluminescence assay and the levels of serum low density lipoprotein-cholesterol(LDL-C) were tested by automatic biochemical analyzer in Nanfang hosipital.IMT of carotid arteries were measured by Color Doppler.The data were analyzed using SPSS statistical software 11.0.Numerical data were generally expressed as((?)±s).Data were analyzed with Independent-Samples T Test and Pearson Linear Correlation.A P value＜0.05 was considered statistically significance.Results:1.The average age in premenopausal and postmenopausal women was (44.60±2.62) and(55.13±3.01) years,respectively.The average serum E2 level was (121.73±53.18) pg/ml in premenopausal women and(23.24±19.82) pg/ml in postmenopausal women.The average serum DHEA level was(12.17±3.09)μg/L in premenopausal women and(7.19±2.37)μg/L in postmenopausal women.The average serum DHEA level was increased with age.Compared with the premenopausal women,the postmenopausal ones achieved a lower serum level of E2, DHEA(P＜0.01).The average serum LDL-C level was(2.89±0.61) mmol/L in premenopausal women and(3.29±0.56) mmol/L in postmenopausal women,The average IMT level was(0.55±0.13) mm in premenopausal women and(0.64±0.15) mm in postmenopausal women.Compared with the premenopausal women,the postmenopausal ones achieved a higher level of LDL-C,IMT(P＜0.01).2.The average serum antioxidation level was(510.50±160.07) U/ml in premenopausal women and(420.41±155.26) U/ml mmol/L in postmenopausal women.The average serum SOD level was(84.84±16.36) U/ml in premenopausal women and(76.96±14.40) U/ml in postmenopausal women.The average serum MDA level was(3.47±1.23) nmol/ml in premenopausal women and(4.03±1.17) nmol/ml in postmenopausal women.The serum SOD level and antioxidation level in the postmenopausal women was decreased than the premenopausal women(P＜0.05). The serum MDA level in the postmenopausal women was increased than the premenopausal women(P＜0.05).3.The average serum ET level was(51.66±10.33) pg/ml in premenopausal women and(62.93±9.12) pg/ml in postmenopausal women.The average serum E-selectin level was(25.06±4.83) pg/ml in premenopausal women and(28.96±5.58) pg/ml in postmenopausal women.The serum level ET,E-selectin in the postmenopansal women was increased than the premenopausal women(P＜0.01).4.There was a correlation between E2 and IMT(r=-0.438,P＜0.001) as well as between E2 and LDL-C(r=-0.416,P＜0.001),Significant correlations were also shown between DHEA and IMT(r=-0.564,P=0.001),between DHEA and age (r=-0.901,P＜0.001),along with between DHEA and LDL-C(r=-0.373,P＜0.001).Conclusion:An increase of intima-media thickness is more likely to occur in females with low estrogen and low DHEA conditions,which may be caused by a metabolic disorder of the lipids.Under this condition,the low-density lipoprotein level would be increased,while the antioxidation and protective effect of estrogen, DHEA in the endothelial cells would be decreased.