Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men.
The role of endogenous sex steroids in the association between male gender and cardiovascular risk remains unclear. We performed a cross-sectional analysis of the role of endogenous testosterone (T) and estradiol (E2), as well as their respective biologically active fractions, in the determination of lipids and lipoproteins in an occupation-based cohort of 715 healthy middle-aged men. Serum T, sex hormone binding globulin (SHBG) and E(2) were measured by immunoassays; free T (FT) and free E2 (FE2) were calculated using a validated equation. Serum total cholesterol (Chol), HDL-cholesterol (HDL-Chol), apolipoproteins A1 (ApoA1), B (ApoB), E (ApoE), ApoE phenotype, lipoprotein a (Lpa), fibrinogen, C-reactive protein (CRP), systolic (SBP) and diastolic blood pressure (DBP) were assessed. Serum levels of T and FT, correlated positively with HDL-Chol and ApoA1 with Spearman correlation coefficients, partialised for age and body mass index (BMI), ranging between 0.14 and 0.17 (P<0.001); FT was associated with total Chol and ApoB levels (r=0.12 for both T and FT; P<0.01). After adjustment for age and BMI, both serum E2 and FE2 levels correlated significantly with ApoE (r=0.25 and r=0.26 for E2 and FE2, respectively; P<0.001). Free and total E2 were associated with both SBP and DBP with correlation coefficients partialised for age and BMI ranging between 0.11 and 0.13 (P<0.01). No correlation was found between any of the studied sex steroids, fibrinogen, Lpa or CRP. In multiple linear regression analyses, T was the most important independent hormonal determinant of HDL-Chol levels, when E2, SHBG and exogenous factors were considered in the model (P<0.01), whereas E2 contributed mostly in the determination of ApoE levels (P<0.001) and SBP (P<0.01). When FT and FE2 were considered in multivariate analyses as independent hormonal variables, FT was the most significant predictor of HDL-Chol (P<0.01) and ApoB (P<0.01) concentrations. Moreover, in the same multivariate model, ApoE (P<0.001) concentration as well as SBP (P<0.001) was most affected by FE2 levels in comparison with FT. In conclusion, our findings do suggest a differential role of T and E2 in the determination of traditional cardiovascular risk factors in healthy middle-aged men. In the determination of both HDL-Chol and ApoB levels endogenous (F)T may be involved, whereas (F)E2 may contribute to the determination of ApoE levels in this study group of 715 healthy middle-aged men. Regarding the observational design of the study, the physiological relationship of the observed associations between sex steroids and cardiovascular risk factors remains to be unravelled.
Van Pottelbergh
I
I
Department of Endocrinology (9K12), Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium
Braeckman
L
L
De Bacquer
D
D
De Backer
G
G
Kaufman
J M
JM
D000328:Adult; D001053:Apolipoproteins / Q000097:blood*; D001794:Blood Pressure; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D003327:Coronary Disease / Q000097:blood / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*
D001053:Apolipoproteins; D008076:Cholesterol, HDL; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D002784:Cholesterol