Correlation Between Plasma Lipoprotein Lp(a)and Sex Hormone Concentrations: A Cross-Sectional Study in Healthy Males

Abstract

High concentrations of lipoprotein Lp(a) have been related to atherosclerotic disease, both at coronary and cerebrovascular levels. Although Lp(a) levels are under a strict genetic control, being inversely related to the molecular weight of apo(a) isoforms, an interference of endogenous sex steroids on Lp(a) metabolism has been hypothesized. The aim of this study was to investigate the interrelationship between plasma Lp(a) and sex hormone concentrations in 98 healthy males, controlled as for their nutritional status by anthropometric measurements. Statistical evaluation was performed employing simple and multiple stepwise regression analysis. No significant correlation was found between Lp(a) levels and fT, E2 and gonadotropins, while they were positively and independently related to LDL-cholesterol and DHEA-S. As for the other lipoproteins, a positive correlation between HDL-cholesterol and E2 and an inverse correlation between triglycerides and SHBG were observed. These data suggest that endogenous testosterone and estradiol do not affect Lp(a) metabolism in males, at least in physiological concentrations. However Lp(a) might be affected by DHEA-S, the most abundant product of the adrenal gland. The positive correlation of HDL-cholesterol to E2 suggests that estrogens play a major role in lipid metabolism also in males, in spite of their low concentrations; more complex to be explained is the finding of an inverse relationship between Tg and SHBG. Further studies are needed in order to clarify the influence of sex steroids on lipid metabolism, mainly on Lp(a), under physiological conditions; population samples homogeneous in terms of apo a isoforms could be the ideal objects of such studies, in order to avoid the great interindividual variability of Lp(a) concentrations.

Variations in the Promoter Region of the Apolipoprotein A-1 Gene Influence Plasma Lipoprotein(a) Levels in Asian Indian Neonates from Singapore

“…It is interesting to note that gender-specific effects of the apoA1 genotypes could already be observed at birth. The possible reasons for such phenomenon has not been elucidated, but the effect of sex hormones would be the likely cause since they are known to affect Lp(a) levels in adults (40,41), although not without controversies (42,43). In our neonatal subjects, there was no significant difference between Lp(a) levels of male and female newborns.…”

Non-genetic influences on lipoprotein(a) concentrations

“…Among healthy men, Lp(a) levels were not associated with endogenous testosterone, free testosterone, or sex-hormone binding globulin (SHBG) [ 78 – 80 ]. However, contradictory results have been reported in two studies for the association between Lp(a) levels and dehydroepiandrosterone sulfate ester (DHEA-S) [ 78 , 80 ], one of the most abundant endogenous androgen steroids. Among men with CAD, Lp(a) levels were significantly negatively associated with free testosterone, but not with DHEA-S [ 81 ].…”

Variation of Lp(a) Plasma Concentrations in Health and Disease~!2009-11-03~!2010-02-06~!2010-09-08~!

“…The increase is temporary if there is no pregnancy and persists in pregnant females [191,193]. Further studies demonstrated that even in males there is no significant correlation between plasma concentrations of estrogen and Lp(a) [164,166,167].…”

“…Experimental studies performed in transgenic mice demonstrated a regulation of the apo(a) gene by sexual steroids and a downregulation by testosterone [163]. In humans endogenous testosterone has no relevant effect on Lp(a) plasma concentration [164][165][166][167][168]. In contrast, administration of testosterone or other anabolic compounds affects a large number of parameters including those of atherogenesis and lipid metabolism [169][170][171].…”