PATHOPHYSIOLOGY AND NATURAL HISTORY ATHEROSCLEROSIS Racial (black-white) comparisons of the relationship of levels of endogenous sex hormones to serum lipoproteins during male adolescence: the Bogalusa

The cross-sectional relationship of endogenous androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate [DHEA-S]), estrogen (estradiol) and progestin (progesterone) to serum levels of lipoprotein cholesterol (very low-density [VLDL], low-density [LDL], and high-density lipoprotein [HDL]) and apolipoproteins (apo A-I and apo B) were studied in white (n 251) and black (n = 258) adolescent boys, ages 1 1 to 17 years, as part of the Bogalusa Heart Study. Black boys had significantly higher levels of estradiol, HDL cholesterol, and apo A-I, and lower levels of androstenedione and VLDL cholesterol than white boys, independent of age and adiposity. Age was correlated strongly with testosterone and androstenedione, and moderately with DHEA-S and estradiol levels in both races. However, only in white boys was age consistently related to VLDL cholesterol (positively), HDL cholesterol (negatively), and apo A-I (negatively). Overall, testosterone was associated inversely with HDL cholesterol and apo A-I in white boys. while progesterone was related positively to apo A-I in both races after adjusting for age and adiposity. However, these relationships were found to differ with age. Partial correlations between levels of sex hormones and lipoproteins adjusted for age and adiposity showed no associations in the 11 to 12 year age group in boys of either race. A significant positive relation of testosterone to VLD, 2holesterol, and inverse relations of testosterone to HDL cholesterol and apo A-I and DHEA-S to HDL cholesterol were apparent only in white boys in the 13 to 14 year age group. Among the older subjects (15 to 17 years old), the relationships of testosterone to HDL cholesterol and androstenedione to apo A-I were positive only in black boys. In addition, a significant positive association between progesterone and apo A-I was noted for both races among boys in the older age group. That the sex hormone-lipoprotein associations vary among different age groups suggests the influence of sexual maturation-related hormonal makeup on lipoproteins. Inherent metabolic differences between the races may account for some of the divergent sex hormone-lipoprotein associations. Circulation 74, No. 6, 1226-1234, 1986 THE INFLUENCE of sex hormones on serum lipid and lipoprotein levels is well known and is considered potentially associated with risk of development of coronary heart disease (CHD).`'2 The incidence of CHD is higher in men than in premenopausal women.3 From the Departments of Medicine, Biochemistry, Public Health and Preventive Medicine, and Biometry and Genetics, Louisiana State University Medical Center, New Orleans, and the Department of Obstetrics and Gynecology, Sinai Hospital and Johns Hopkins School of Medicine, Baltimore. Supported by research grants HL-02942 and the National Research and Demonstration Center Arteriosclerosis (HL-15103) from the National Heart, Lung, and Blood Institute of the U.S. Public Health Service. Address for correspondence: Gerald S. Berenson, M.D., Department of Medicine, LSU Medical Center, 1542 Tulane Ave., New Orleans, LA 70112. Received May 20, 1986; revision accepted Sept. 11, 1986. 1226 Women with normal ovarian function have lower levels of very low (VLDL) and low-density lipoproteins (LDL) and higher levels of high-density lipoproteins (HDL) than men, factors considered to be protective against CHD.4 Furthermore, it has been suggested that the relatively greater protection of black compared with white men from CHD is due partly to their higher HDL levels.5 However, it is not known whether levels of sex hormones have any role in determining the racerelated differences in lipoproteins. Profound changes in lipoproteins occur in children during sexual maturation before adult patterns are established.6 ' Both black and white girls have higher levels ofVLDL and LDL cholesterol as compared with boys before sexual maturation. During sexual maturaCIRCULATION by gest on A ril 6, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-ATHEROSCLEROSIS tion, levels of HDL and LDL cholesterol decrease in both races, but the decrease in HDL cholesterol is much greater in white boys. Recent studies in children demonstrate that endogenous sex hormones relate to lipoprotein levels,°10 and may account for the sexrelated divergence of lipoprotein profiles after puberty. 10 However, the question arises whether the relation of levels of endogenous sex hormones to those of lipoproteins is the same in both races. The purpose of this report is to evaluate the relation of endogenous androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate [DHEAS]), estrogen (estradiol), and progestin (progesterone) to serum levels of lipoprotein cholesterol (VLDL, LDL, and HDL) and apolipoproteins (apo A-I and apo B) in black and white adolescent boys living under similar environmental conditions. Materials and methods Population. The Bogalusa Heart Study is a long-term, population-based study of cardiovascular disease risk factors from birth through 26 years of age in the biracial community (64% white, 36% black), Bogalusa, LA.'1 Data collected from the fourth cross-sectional examination (1981-1982) of school-age children (n = 3314, 80% participation) were used in the current analyses. All analyses were restricted to boys between the ages of 11 and 17 years. To assess the relationship between levels of sex hormones and serum lipoproteins during adolescence, a random sample of whites was selected to provide approximately equal numbers of blacks (n = 258) and whites (n = 251) in this age group. These samples represent 48% (white) and 90% (black) of all boys in this age range who were examined. Assessment of sexual maturation. Sexual maturation was determined during physical and anthropometric examinations by visual assessment of secondary sex characteristics according to the method of Tanner.'2 The ratings of sexual maturation ranged from 1 (no development) to 5 (complete development) according to the stages of male genitalia development. Collection of blood specimens. Children were instructed to fast for 12 to 14 hr before venipuncture. Antecubital venous blood was drawn separately for lipoprotein and sex hormone assays; serum samples were prepared in tubes containing thimerosal (Aldrich Chemical Co., Milwaukee, WI). Serum for lipoprotein measurements was kept at 40 C until analysis the following day in the core laboratory in New Orleans; the serum samples for determination of sex hormone levels were kept frozen (-20° C) and sent by air to Baltimore (Dr. G. S. Sundaram). Serum lipids, lipoprotein cholesterol, and apolipoprotein determinations. Cholesterol and triglycerides were determined in a Technicon AutoAnalyzer II (Technicon Instrument Corp., Tarrytown, NY) according to the Laboratory Manual of the Lipid Research Clinics Program.13 The laboratory has been designated as standardized by the Center for Disease Control, Atlanta, and currently is in the surveillance phase of its qualitycontrol program. Serum VLDL, LDL, and HDL cholesterol levels were measured by a combination of heparin-calcium precipitation and agar-agarose gel electrophoretic methods. A detailed description of this method, including measurement errors and its application in the Bogalusa Heart Study, has already been reported. 1'4 The levels of apo B and apo A-I in whole serum were assayed Vol. 74, No. 6, December 1986 by an electroimmunoassay procedure. Antibodies to LDL (d 1.03 to 1.05 g/ml) and apo A-I raised in goats were used. This method, including measurement errors, has been described elsewhere in detail.15 The laboratory is participating in the apo A-I and apo B standardization program of the International Union of Immunological Societies-CDC--NHLBI. Serum sex hormone determinations. Estradiol-17,8 was quantitated by the radioimmunoassay (RIA) method with rabbit antiserum against estradiol-17,3-3-carboxymethylether-BSA and a 1251-labeled antigen by a double antibody technique.'6 Testosterone, progesterone, and DHEA-S were quantitated with commercial RIA kits prepared by Immuchem Corp., Diagnostic Products, and Radio Assay System Laboratories, Inc., respectively. The levels of androstenedione were deternined by the RIA method. 17 The antiserum had moderate cross-reaction with 5-a-androstenedione, which has no significant serum levels and very low cross-reaction with DHEA, and generally less than 1% affinity for all related steroids. The laboratory participates in the endocrinology and metabolism quality-control program administered by the American Association of Clinical Chemistry. As in our previous study,'0 samples were analyzed in duplicate along with commercial lowand high-level quality-control samples. Overall measurement errors from these quality-control samples varied from 6% to 13%. Statistical analyses. Since several of the sex hormone and lipoprotein distributions were positively skewed, nonparametric tests were used in several analyses. Racial differences in levels of the sex hormones and lipoproteins were assessed by Wilcoxon tests'8 or analysis of covariance, adjusting for age and subscapular skinfold thickness. Because levels of several of the sex hormones and serum lipoproteins differed between the races, subsequent analyses were performed separately for black and white boys. Spearman correlations were used to examine the relationships of age, subscapular skinfold thickness, and ponderal index to levels of sex hormones. Within each race, associations between the serum lipoproteins and sex hormones were then examined with the use of correlation coefficients. Partial correlations were also calculated to assess whether the observed associations existed independently of age and subscapular skinfold thickness. Polynomial regression models,'9 containing both linear and quadratic terms, were also used to evaluate the relationships between the sex hormones and serum lipoproteins. Because of the nonlinearity of certain relationships, several of the sex hormone-serum lipoprotein associations were further examined within age groups.