The Investigation On The Relationship Between The Sex Hormone, The Androgen Receptor And The Metabolic Syndrome In Aging Men

BackgroundBased on the 26-year follow-up for people aged 35-84, the Framingham Heart Study revealed that mortality of CAD in man was twice of that in female. Sixty percent of events from CAD occurred in man and the age when the symptomatic CAD developed in men was 10 years earlier than in female. So, male, as well as hypertension, diabetes, dyslipidemia, obesity and age were defined as the independent risk factors of cardiovascular diseases(CVD). However, metabolic syndrome (MS), which was consisted of various kinds of diseases and conditions including hypertension, pathoglycemia, dyslipidemia and obesity, could induce directly or aggravate the development of CVD. NCEP ATP III guidelines defined DM as CAD risk equivalent. As male was a risk factor of CVD, was there correlation between the male and the other risk factors of CVD, especially the MS which was a complex of many risk factors? Epidemiology data showed that there was a positive correlation between the development of CVD and age. It was reported that four fifth of patients who died of myocardial infarction were older than 65. Furthermore, studies had demonstrated that sex hormone levels in men changed with age, too. So, it was supposed that there was some correlation between the variation of sex hormone and CVD. As we know, sex hormones couldn't played their physiological actions until they bond with the sex hormone receptors. So, the variations of sex hormone receptors may be of importance. Based on these presumptions, we designed and conducted this study. In this study, we tried to clarify the relationship between the biological effects of sex hormone and MS in old men and provide the theory evidences for the prevention andtreatment of MS. Objectivesi. Investigating on the profile of sex hormone level in old men with MS;ii. Evaluation the relationship between the sex hormone and every component ofMS in ageing man; iii. Assessment of the level of androgen receptor (AR) , the relationship betweenAR and each component of MS in elderly male; iv. Presumption the predictors of MS in ageing man. ObjectsIn total, there were 230 old men who were older than 60 enrolled into the study. Among these old men, 102 (age 62-92, 71.38±5.154)were healthy; 128 (age 60～87, 73.03±6.26) suffered from MS. The standard of healthy old man was established by presbyatrics branch of CMS in 1995; the standard of MS was supposed by diabetes branch of CMS in 2004. Methodsi. Measurement of plasma sex hormoneA venous blood sample (4 ml) was taken in the morning (7:30-8:30); serum samples were obtained by centrifugation and immediately frozen at - 80°C pending further analysis. Total testosterone (TT), estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by chemoluminescence analysis system. Free testosterone (FT), dehydroepiandrosterone sulphate (DHAE-S) and sex hormone binding globulin (SHBG) were measured by the enzyme-linked immunosorbent assay technique.ii. Measurement of fasting blood sugar (FBS) and lipidBlood glucose and lipid were measured by chromatometry (Automatic Analyzer, Hitachi 7600).iii. Measurement of fasting serum insulinSerum insulin was measured by Solid-phase, two-site chemiluminescent immunometric assay.iv. Measurement of androgen receptorAndrogen receptor on the peripheral leukocyte was measured by indirectimmunofluorescent labeling with flow cytometry (expressed by meanfluorescence intensity and positive rate of androgen receptor).Resultsi. The body weight, BMI, waistline(WL), hip circumference(HC), WHR andsystolic blood pressure in MS group were higher than those in healthy group.ii. DHAE-S, TT, SHBG, FT, AR% and AR fluorescence intensity in MS groupwere lower than healthy group, however, FSH, E2 in MS group were higher thanhealthy group.iii. In old men especially the men over 80, WL, HC, WHR and systolic bloodpressure increased with aging, however, DHEAS, TT, SHBG, FT and ARdecreased with aging; E2/T, LH and FSH also increased with aging.iv. Age was negatively correlated with DBP, FT and AR%; positively correlatedwith SBP and E2.v. E2 increased with BMI, especially in the obesity group; however, DHEAS, TT,SHBG and AR decreased with BMI, also pronounced in obesity group.vi. Age, body weight, BMI, HC, WHR, SBP, E2 and FSH increased with WL,especially when the WL were more than 97cm; DHEAS, SHBG and ARdecreased with WL, also pronounced when the WL were more than 97cm.vii. Insulin sensitivity index (ISI) was negatively correlated with FBS and insulinand LDL-C; positively correlated with insulin resistance index (IRI) and SHBG.viii. IRI was negatively correlated with HC and SHBG; positively correlated withFBS and insulin and ISI.ix. The correlations between the sex hormone and AR in old men and componentsof MS are as follows:TT was negatively correlated with DBP and was positively correlated with ISI,even after adjusted for age and BMI.There were no significant correlations between FT and all components of MS.DHEAS was negatively correlated with SBP and positively correlated withsaccharifying serum protein.AR fluorescence intensity was negatively correlated with SBP and was positivelycorrelated with ISI.AR% was negatively correlated with saccharifying serum protein, SBP and waspositively correlated with FBS.SHBG was negatively correlated with BMI and IRI and was positively correlatedwith INS.E2 was negatively correlated with SBP and was positively correlated with bodyweight and TG.E2/TT was negatively correlated with ISI.FSH was negatively correlated with INS.There were no significant correlations between LH and all components of MS.x. DHEAS and SHBG entered into the Logistic regression equation and they werenegatively correlated with the development of MS, but OR less than 1.Conclusionsi. In old men, DBP, FT and AR decreased with aging; however, the SBP and E2increased with aging. The old men over 80 had high level of SBP and WHR andlow level of DHEAS, TT, SHBG, FT and AR.ii. In old obesity men, the E2 level increased and DHEAS, TT, SHBG and ARlevel decreased.iii. The old men whose WL were more than 97cm had high level of body weight,BMI, HL, WHR, SBP, E2 and FSH; however, the level of DHEAS, SHBG and ARwere low.iv. The old men with MS had low level of DHEA-S, TT, SHBG, FT and AR;however, the FSH and E2 level was high.v. Among the seven kinds of sex hormones in old men, TT and SHBG correlatdwith the components of MS more significantly.vi. Low level of DHEAS and SHBG may be the potential risk factors of MS in oldmen.