Relationships of serum lipoproteins and apoproteins to sex hormones and to the binding capacity of sex hormone binding globulin in healthy Finnish men

We have determined the levels of serum sex hormones, the binding capacity of sex hormone binding globulin (SHBG), urinary estrogens, serum lipids, lipoproteins, and apolipoproteins A-I, A-II, and B in 30 healthy middle-aged Finnish men with similar dietary habits. Serum levels of total testosterone, free testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), and the binding capacity of SHBG were all positively correlated to high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) (r = .43 to .80, P less than 0.05 to 0.001). Total testosterone and 5 alpha-DHT showed a positive correlation to the ratio of apo A-I to Apo A-II (r = .37, P less than 0.05 and r = .58, P less than 0.01, respectively). Serum estradiol levels were negatively correlated to serum total cholesterol, low density lipoprotein cholesterol (LDL), and Apo B (r = -.51 to -.56, P less than 0.01). Moreover, serum free estradiol was negatively correlated to HDL-C and Apo A-I (r = -.46 and r = -.50, P less than 0.01). In multiple linear regression analysis, 5 alpha-DHT was the most significant independent determinant of HDL-C and apo A-I levels when androgens, luteinizing hormone, estradiol, binding capacity of SHBG, and exogenous factors such as age, body mass index (BMI), smoking, alcohol consumption, and diet were taken into account. Multivariate analysis also demonstrated that both total and free estradiol were inversely related to serum Apo B levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous postmenopausal hormones and serum lipids: the atherosclerosis risk in communities study

Previous studies have revealed that exogenous estrogen has a beneficial effect on the lipid profile; however, studies examining the relation between endogenous hormones and lipid profiles in postmenopausal women have yielded conflicting results. We sought to characterize the cross-sectional relationship between endogenous hormones and lipid parameters in postmenopausal women with significant (cases, n = 156) and minimal (controls, n = 172) carotid atherosclerosis not taking hormone therapy in the Atherosclerosis Risk in Communities Study. Endogenous hormone status was assessed by measuring levels of estrone, total testosterone, androstenedione, dehydroepiandrosterone sulfate, and SHBG. Free testosterone was estimated using the free androgen index (total testosterone/SHBG). Lipid parameters assessed included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. We found that SHBG was significantly associated with a more favorable lipid profile, including lower total and LDL cholesterol and triglycerides and higher HDL cholesterol among controls. This association was less prominent among cases where SHBG was only associated with higher triglycerides and lower HDL cholesterol. The free androgen index was associated with a more atherogenic lipid profile, including increased LDL cholesterol among controls and increased total and LDL cholesterol and triglycerides among cases. These relations were independent of demographic and metabolic factors and health behaviors. In contrast to controls, estrone was associated with higher total cholesterol and triglycerides among cases in multivariate analyses. Our data suggest that endogenous sex hormones may play a role in regulating lipid metabolism in postmenopausal women.     

Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN

We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH, estradiol, testosterone, and SHBG. SHBG was used to calculate the free estradiol index and free androgen index. We studied 3,200 women, aged 42-52 yr, in the Study of Women's Health Across the Nation, a prospective multiethnic study of the menopausal transition. We measured the hemostatic factors, fibrinogen, factor VIIc, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1), as well as glucose and insulin to calculate insulin resistance. After adjustment for body mass index, site, and ethnicity, SHBG was correlated with PAI-1 (partial r = -0.30) and t-PA (partial r = -0.12). Although testosterone was associated with t-PA (partial r = 0.13) and PAI-1 (partial r = 0.07), free androgen index was strongly correlated with t-PA (partial r = 0.18) and PAI-1 (partial r = 0.26). SHBG modified the association of hemostatic factors with insulin resistance. Women with greater insulin resistance had lower SHBG and higher PAI-1. Estrogen measures were not associated with insulin resistance. The influence of sex hormones on hemostatic factors and insulin resistance is poorly understood. SHBG, which influences the amount of bioavailable hormone, significantly modified the association of PAI-1 and t-PA with insulin resistance. The longitudinal Study of Women's Health Across the Nation will help us discern whether this interaction contributes to heart disease and diabetes among postmenopausal women.     

Endogenous sex hormones and glucose tolerance status in postmenopausal women

CONTEXT: In postmenopausal women, endogenous estradiol (E2) and free testosterone (T) have been positively associated with glucose intolerance and type 2 diabetes. Most studies have not examined these associations in a large group of postmenopausal women. OBJECTIVE: The objective was to examine the association between endogenous sex hormones and glucose tolerance in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 1973 postmenopausal women ages 45-84 yr, not taking hormone replacement therapy, in the Multi-Ethnic Study of Atherosclerosis baseline examination. MAIN OUTCOME MEASURES: Impaired fasting glucose (IFG) and diabetes were defined based on fasting blood sugar and/or treatment for diabetes. In women with normal glucose tolerance, insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Increasing quartiles of bioavailable T and E2 and decreasing quartiles of SHBG were associated with significantly increased odds of IFG and diabetes (all P for trend<0.001). Except for the association of bioavailable T with diabetes, the other associations persisted after multivariable adjustment. Although higher dehydroepiandrostenedione (DHEA) was associated with greater odds of IFG (P for trend=0.02), it was not associated with diabetes. Of 1100 women with normal glucose tolerance, E2 and DHEA were positively associated, and SHBG was inversely associated with HOMA-IR (all P<0.001) after multivariable adjustment. Bioavailable T was associated with HOMA-IR (P<0.001), but not fasting glucose. CONCLUSION: Of postmenopausal women, endogenous bioavailable T, E2, and DHEA were positively associated and SHBG was negatively associated with insulin resistance.     

Associations of abdominal adiposity, fasting insulin, sex hormone binding globulin, and estrone with lipids and lipoproteins in post-menopausal women

The associations of abdominal adiposity, fasting serum levels of insulin, and sex hormones with blood lipids, lipoproteins, and apolipoproteins A-I and B were studied cross-sectionally in 75 healthy, postmenopausal white women. In univariate analyses, abdominal adiposity (increased waist-to-hip girth ratio) and fasting insulin concentrations were negatively and significantly associated (P less than 0.05) with plasma high density lipoprotein cholesterol (r = -0.47 and -0.38, respectively) and apolipoprotein A-I (r = -0.37 and -0.36), and positively associated with log triglycerides (r = 0.54 and 0.33) and apolipoprotein B (r = 0.43 and 0.22). Sex hormone binding globulin was positively and significantly associated with high density lipoprotein cholesterol (r = 0.32) and negatively associated with log triglyceride (r = -0.45) and apolipoprotein B (r = -0.36). Estrone was positively and significantly associated with high density lipoprotein cholesterol (r = 0.27), apolipoprotein A-I (r = 0.23) and negatively associated with low density lipoprotein cholesterol (r = -0.24) and apolipoprotein B (r = -0.25). Total estradiol, free estradiol, free testosterone, and total testosterone were more weakly associated with the lipid measures. In multivariate analyses, abdominal adiposity remained significantly associated with high density lipoprotein cholesterol, log triglycerides, apolipoproteins A-I and B after adjustment for sex hormone binding globulin, estrone, and insulin concentrations. Insulin remained associated only with apolipoprotein A-I after adjustment for abdominal adiposity, estrone, and sex hormone binding globulin. Sex hormone binding globulin remained marginally associated with log triglyceride (P = 0.07) after adjustment for the remaining three factors. Estrone remained significantly associated with high density lipoprotein cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

The association of endogenous sex hormones with lipoprotein subfraction profile in the Multi-Ethnic Study of Atherosclerosis

The traditional lipid profile differs by sex hormone levels. However, associations of sex hormones with lipoprotein subfractions, which may more accurately represent metabolic pathways to atherosclerosis, are not well studied. We quantified the cross-sectional associations of endogenous sex hormones with lipoprotein subfractions in 3143 men and 2038 postmenopausal women who were not on hormone replacement therapy, aged 45 to 84 years, in the Multi-Ethnic Study of Atherosclerosis baseline examination. Particle sizes and numbers of very low-density (VLDL), low-density (LDL), and high-density (HDL) lipoproteins were measured by nuclear magnetic resonance. In both men and women, after multivariable adjustment, higher sex hormone binding globulin (SHBG) levels are associated with smaller, fewer VLDL; larger, fewer LDL; and larger, more numerous HDL particles, whereas higher endogenous estradiol levels are associated with smaller VLDL and smaller, more numerous HDL and LDL particles (all P < .05). Testosterone (adjusted for SHBG) is associated with smaller VLDL particles in men but not women (sex difference P = .040). Higher dehydroepiandrosterone levels are associated with more numerous, smaller VLDL particles only in women (sex difference P = .030, .004, respectively). In conclusion, we found sex differences in the association of endogenous androgens with lipoprotein particle sizes and numbers. Higher endogenous estradiol, but lower SHBG, is associated with a more atherogenic lipoprotein particle profile. These findings highlight the potential to improve the lipoprotein profile with sex hormones, but emphasize the intricacies of the interactions.     

Endogenous hormones and coronary heart disease in postmenopausal women

The association between serum levels of endogenous estrogens in postmenopausal women and the subsequent risk of coronary heart disease (CHD) was examined in a prospective case-control study nested within the New York University Women's Health Study (NYUWHS). The NYUWHS is a prospective cohort study of 14,274 healthy women enrolled between 1985 and 1991. A total of 99 women who were postmenopausal and free of cardiovascular disease at enrollment and who subsequently experienced CHD, defined as non-fatal myocardial infarction (MI), fatal CHD, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG), were matched 1:2 by baseline age, blood sampling date, and postmenopausal status to controls who remained free of CHD as of the date of diagnosis of the matching case. Biochemical analyses for total estradiol, estrone, percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), and SHBG were performed on pre-diagnostic stored serum samples. Participants had not used any hormone medications in the 6 months prior to blood collection. In the model adjusting only for matching factors, the risk of CHD in the top tertile of calculated bioavailable estradiol was elevated compared with the bottom tertile (OR=2.10; 95% CI=1.13-3.90, P for trend=0.03), and the risk in the top tertile of SHBG was reduced (OR=0.50, 95% CI=0.28-0.92, P for trend<0.01). However, these associations disappeared after adjusting for baseline hypertension status, body mass index, and serum cholesterol levels. These findings suggest that circulating estradiol and SHBG are not associated with CHD risk in postmenopausal women beyond what can be explained by the variation in hypertension status, BMI, and cholesterol.     

Racial disparities in metabolism, central obesity, and sex hormone-binding globulin in postmenopausal women

Increased total and intraabdominal fat (IAF) obesity as well as other metabolic conditions associated with the insulin resistance syndrome (IRS) are related to low levels of sex hormone-binding globulin (SHBG) in young and older Caucasian (CAU) and young African-American (AA) women. We examined whether postmenopausal AA women, a population with a high incidence of obesity and IRS despite low IAF, would have higher levels of circulating SHBG compared with CAU women, and whether there would be negative relationships between indexes of obesity and risk factors associated with IRS and SHBG levels. We measured body composition, SHBG, free testosterone, leptin, glucose tolerance, insulin, and lipoprotein lipids in 55 CAU (mean +/- SD, 59 +/- 7 yr) and 35 AA (57 +/- 6 yr) sedentary women of comparable obesity (48% body fat, by dual energy x-ray absorptiometry). Compared with CAU women, AA women had larger waist (101 vs. 96 cm), larger fat mass (44.9 +/- 8.8 vs. 39.9 +/- 8.1 kg), larger sc fat area (552 +/- 109 vs. 452 +/- 109 cm(2)), and lower IAF/SC ratio (0.28 +/- 0.12 vs. 0.38 +/- 0.15; P < 0.01), but similar waist to hip ratio (0.83). Both groups had similar SHBG (117 vs. 124 nmol/L) and free testosterone (3.7 vs. 3.4 pmol/L) levels, but AA women had a 35% higher leptin, 34% higher fasting insulin, and 39% greater insulin response to a glucose load (P < 0.05) compared with CAU women. In CAU, but not AA, women SHBG correlated negatively with body mass index (r = -0.28; P < 0.05), waist (r = -0.36; P = 0.01), IAF (r = -0.34; P = 0.01), and insulin response to oral glucose (r = -0.37; P < 0.05) and positively with high density lipoprotein cholesterol (r = 0.30; P = 0.03). The relationship between insulin area and SHBG in CAU women disappeared after adjusting for IAF, whereas the relationship between high density lipoprotein cholesterol and SHBG persisted after adjusting for IAF, but not for fat mass. Leptin was positively related to fat mass (P < 0.05) in both groups, but it was related to insulin only in the Caucasian women (P< 0.01). There was a racial difference in the slopes (P< 0.05) of the relationships of leptin to fat mass (P < 0.05). Racial differences in leptin disappeared after adjustment for fasting insulin. These results suggest that the metabolic relationships between total and regional obesity, glucose, and lipid metabolism with SHBG in CAU women are different from those in postmenopausal obese AA women.     

Testosterone and estradiol among older men

CONTEXT: Testosterone and estradiol levels decline with age in men. This change may affect multiple clinical outcomes, but there have been few reports of the distribution and correlates of testosterone and estradiol concentrations in elderly men. OBJECTIVE: The purpose of these studies was to assess sex steroid levels in a large cohort of older men. DESIGN: We conducted a cross-sectional cohort evaluation. SETTING: Community-dwelling men were studied at six academic medical centers in the United States. PARTICIPANTS: The Osteoporotic Fractures in Men Study is a prospective cohort of men aged at least 65 yr. In these studies, a randomly selected stratified subsample of 2623 participants was analyzed. MAIN OUTCOME MEASURES: We assessed levels of total and free testosterone and estradiol and SHBG. Results: Age was inversely associated with free testosterone and free estradiol levels (P for trend = 0.001 for both). Notably, at any age, there was substantial variation in levels of each hormone. Free testosterone levels were lower in men with greater body mass index, lower SHBG, and poorer self-reported health status and in those of Asian race. Free estradiol concentrations were lower in men with lower body mass index and higher SHBG levels. Free estradiol and free testosterone were modestly correlated (r = 0.20; P < 0.001), but at any level of free testosterone, there was considerable variation in free estradiol levels. CONCLUSIONS: This is the largest cohort of older men in which sex steroid levels are available, and it demonstrates that testosterone and estradiol, and their free fractions, tend to decline with age even among older men. However, substantial variation is also present. The relationships between sex steroid levels and their consequences in aging are likely to be complex.     

Estradiol/Testosterone Imbalance: Impact on Coronary Heart Disease Risk Factors in Postmenopausal Women

Objective: Several groups have reported the important role of the estradiol/testosterone (E(2)/T) ratio in benign prostatic hyperplasia and cerebral vessels. However, there has been no study on the role of the E(2)/T ratio in women with coronary heart disease (CHD). This study aimed to evaluate the association among the ratio of sex hormones and known risk factors of atherosclerosis in postmenopausal women with CHD. Methods: 114 controls and 124 postmenopausal women with CHD were selected for this study. Serum levels of estradiol, testosterone, aromatase, sex hormone-binding globulin (SHBG), lipid-lipoprotein profile and high-sensitivity C-reactive protein were determined. Results: Compared with the control, the E(2)/T ratio decreased from 5.35 ± 2.78 to 3.88 ± 2.51 (p < 0.0001). Multiple linear regression analysis showed that the E(2)/T ratio was negatively associated with total cholesterol, low-density lipoprotein cholesterol (LDL-c) and the atherogenic index of plasma, but positively associated with high-density lipoprotein cholesterol (HDL-c) and HDL-c/LDL-c (for all, p < 0.0001). We found that there was a negative correlation between the E(2)/T ratio and aromatase (r = -0.192, p = 0.032) and a positive correlation between aromatase and SHBG (r = 0.938). Conclusion: The balance of the serum E(2)/T ratio was broken in the women with CHD, and an imbalanced E(2)/T ratio showed a strong association with cardiovascular risk factors in postmenopausal women with CHD.     

Effect of estrogen-progestin replacement therapy on plasma lipids and lipoproteins in postmenopausal women

Serum levels of cholesterol (Chol), triglycerides (TG), low-density lipoprotein cholesterol (LDL) high-density lipoprotein cholesterol (HDL), both apolipoproteins A1 and B (Apo A1, Apo B), follicle-stimulating hormone (FSH) luteinizing hormone (LH), estradiol (E2), progesterone (P), testosterone (T) and steroid hormone binding globulin (SHBG) were measured in postmenopausal women, before and after four different estrogen-progestin replacement therapies. Each woman was her own control to avoid genetic or socioeconomic differences. Our results showed that serum E2 and TG significantly increased and serum FSH, LH, LDH, Apo B, and Chol significantly decreased after all treatments. Serum P and T did not significantly change after any of the treatments. HDL, Apo A1 and SHBG significantly increased in the groups treated with medroxiprogesterone acetate (MPA) but not in the group treated with Norgestrel. We conclude that estrogen-progestin replacement therapy in postmenopausal women leads to profound and beneficial changes in plasma lipids and lipoproteins and that treatments with cyclic or continuous MPA could provide greater protection against coronary heart disease (CHD).     

Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case-control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.     

Sex hormone levels and subclinical atherosclerosis in postmenopausal women: the Multi-Ethnic Study of Atherosclerosis

We examined cross-sectional associations between sex hormones and carotid artery intimal-medial thickness (cIMT) and coronary artery calcium in women in the Multi-Ethnic Study of Atherosclerosis. Serum testosterone, estradiol, sex hormone binding globulin (SHBG), and dehydroepiandrosterone levels were measured in 1947 postmenopausal women aged 45-84 years (30% White, 14% Chinese-American, 31% Black, and 25% Hispanic) and not on hormone therapy. Using multiple linear regression we evaluated associations between log(sex hormone) levels and log(cIMT) adjusted for age, ethnicity, body mass index (BMI) and cardiac risk factors. Associations between sex hormone levels and the presence and extent of coronary calcium were evaluated. Total and bioavailable testosterone were positively associated with common cIMT independent of age, BMI, hypertension, smoking, HDL-cholesterol, LDL-cholesterol and insulin sensitivity (p=0.009 and p=0.002, respectively). SHBG was negatively associated with common cIMT (p=0.001) but further adjustment for BMI, cardiovascular risk factors, and LDL- and HDL-cholesterol removed significance. Estradiol and dehydroepiandrosterone were not associated with common cIMT. Sex hormones were not associated with presence of coronary calcium. Among women with measurable coronary calcium, higher SHBG (p=0.012) and lower bioavailable testosterone (p=0.007) were associated with greater coronary calcium score. No heterogeneity by ethnicity was found. In postmenopausal women, testosterone is independently associated with greater common cIMT. SHBG is negatively associated and this may be mediated by LDL- and HDL-cholesterol. In contrast, SHBG and testosterone were associated with extent of coronary calcium but in the opposite direction compared to carotid intimal-medial thickness. These differences warrant further evaluation.     

Association of endogenous sex hormones and insulin resistance among postmenopausal women: results from the Postmenopausal Estrogen/Progestin Intervention Trial

Most studies of sex hormones and insulin resistance (IR) have focused on androgens; few have examined the association of endogenous estrogens and IR. We determined the cross-sectional association of endogenous levels of total and bioavailable testosterone and estradiol and SHBG with IR among 845 healthy, postmenopausal women aged 45-65 yr. Women were within 10 yr of menopause and not using hormone replacement therapy. Total adiposity was estimated by body mass index, visceral adiposity by waist to hip ratio (WHR), and IR by the homeostasis model assessment. We defined homeostasis model assessment-IR as the highest quartile (cutpoint, 2.1) of the distribution in this cohort. In logistic regression analyses, the odds for IR were significant and increased in a dose-response fashion across each quartile of total estradiol, bioavailable estradiol, and bioavailable testosterone (all P < 0.001 for linear trend). These associations remained significant after adjusting for WHR; adjusted odds ratios were 4.0, 6.1, and 2.7 for total estradiol, bioavailable estradiol, and bioavailable testosterone, respectively, comparing the highest to the lowest quartile (all P < 0.001). Adjusting for body mass index and WHR together eliminated the linear association of IR with total estradiol and bioavailable testosterone, but the association with bioavailable estradiol remained (adjusted odds ratio, 2.7; P < 0.001, comparing the highest to the lowest quartile). IR was not associated with total testosterone before or after adjusting for adiposity. Lower SHBG levels were associated with higher odds of IR, independent of adiposity. These results suggest that estrogen may be equally or more important than testosterone in the pathway to IR in healthy, young postmenopausal women, with differences not entirely explained by body size.     

Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women

Although an association between the metabolic syndrome and hyperandrogenism has been suggested in women with polycystic ovarian syndrome, few studies have investigated this relationship in postmenopausal women. We measured estradiol, testosterone, and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI) in 212 postmenopausal women not using hormone therapy in the Women's Health Study. A modified definition of the metabolic syndrome (3 or more of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein, elevated blood pressure, and abnormal glucose metabolism) from the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults was used. Women with the metabolic syndrome had higher mean levels of estradiol, testosterone, and FAI values and lower SHBG levels. Higher FAI and lower SHBG were associated with all components of the metabolic syndrome. After adjustment for BMI and other factors, women in the highest tertile of FAI had an odds ratio of 12.6 (95% confidence interval, 3.8-41.6) for the metabolic syndrome, whereas those in the lowest SHBG tertile had an odds ratio of 7.3 (95% confidence interval, 2.7-19.8). When stratified by body mass index, the associations with high FAI and low SHBG remained significant even in women with body mass index less than 26.7 kg/m2. An androgenic hormone profile is associated with both the individual components of the metabolic syndrome and clustering of metabolic abnormalities in postmenopausal women.     

Relationship of sex hormone binding globulin to overall adiposity and body fat distribution in a biethnic population

Previous data have indicated that decreased sex hormone binding globulin (SHBG) is associated with increased overall and upper body adiposity and higher levels of glucose, insulin and triglyceride (TG) and decreased levels of high-density lipoprotein (HDL) cholesterol. Since Mexican Americans have greater overall and upper body adiposity, higher rates of non-insulin-dependent diabetes mellitus, higher TG and lower HDL levels than non-Hispanic whites, we postulated that they would also have lower levels of SHBG. We measured total testosterone and total estradiol using a commercial radioimmunoassy and SHBG using a dextran-coated charcoal technique in premenopausal women (61 Mexican American and 39 non-Hispanic white) as part of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors. There were no significant ethnic differences in total testosterone or total estradiol. SHBG, however, was lower in Mexican American (0.285 micrograms/dl) than in non-Hispanic white women (0.429 micrograms/dl) (P = 0.009). After adjustment for body mass index (BMI), ratio of waist-to-hip circumference (WHR) and ratio of subscapular-to-triceps skinfolds (centrality index), SHBG remained lower in Mexican Americans (0.307 micrograms/dl) than in non-Hispanic whites (0.396 micrograms/dl), although this difference was no longer statistically significant (P = 0.083). BMI, WHR and centrality index were all negatively associated with SHBG (P less than 0.01). The lower levels of SHBG in premenopausal Mexican American women compared to non-Hispanic white women may reflect greater in-vivo androgenicity and may be related to a variety of metabolic abnormalities seen in this ethnic group.     

Cardiovascular disease risk characteristics of the main polycystic ovary syndrome phenotypes

The aim of this article was to evaluate the clinical, endocrine, and cardiovascular disease risk profile differences among main polycystic ovary syndrome (PCOS) phenotypes. One hundred and thirty-nine consecutive women were included in the study. Body mass index (BMI), serum follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, estradiol, testosterone, dehydroepiandrosterone sulfate, fasting glucose, low density lipoprotein (LDL-C), total cholesterol, high density lipoprotein (HDL-C) high sensitive CRP, c-peptide, insulin, insulin sensitivity and carotid intima thickness were compared among different phenotype groups of PCOS: Group 1-PCO (polycystic ovaries)-anovulation (n = 34), Group 2-Hyperandrogenemia (HA)-anovulation (n = 30), Group 3-HA-PCO (n = 32), and Group 4-HA-PCO-anovulation (n = 43). Statistically significant differences among the different phenotype groups in terms of waist hip ratio, total cholesterol, LH, estradiol, fasting glucose, progesterone, free testosterone, and carotid intima media thickness were observed. The lowest mean CIMT was observed in Group 3, and the highest fasting glucose levels were in Group 4, while the lowest mean free testesterone was measured in Group 1. BMI, LDL-C, and total cholesterol showed significant positive correlations with CIMT (r = 0.411, P = 0.001; r = 0.258, P = 0.006; r = 0.199, P = 0.033). The lowest LDL-C, total cholesterol, and BMI were found in Group 3, but differences were not statistically significant. High-sensitive CRP levels were similar among the groups (P = 0.103). Group 3 PCOS with PCO and hyperandrogenemia phenotype has lower cardiovascular disease risk compared to other phenotypes.     

Endogenous sex hormone levels in postmenopausal women undergoing carotid artery endarterectomy

OBJECTIVE: To study the endogenous sex hormone levels in natural postmenopausal women and their association with the presence of internal carotid artery (ICA) atherosclerosis. DESIGN: Case-control study METHODS: We compared 56 patients with severe ICA atherosclerosis referred for carotid artery endarterectomy (CEA) with 56 age-matched control subjects free of severe atherosclerotic disease. The presence of atherosclerosis was determined by high-resolution B-mode ultrasound. Metabolic parameters and sex hormones were measured or calculated: total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, glucose, insulin, quantitative insulin sensitivity check index, insulin resistance index, IGF-I, DHEA, DHEA sulfate (DHEA-S), free testosterone, total testosterone, estrone, estradiol, androstenedione, and sex hormone-binding globulin. RESULTS: The cases had statistically significant lower levels of both total testosterone (0.23 +/- 0.12 vs 0.31 +/- 0.20 microg/l, P = 0.043) and free testosterone (3.42 +/- 1.94 vs 4.59 +/- 2.97 ng/l, P = 0.009) and significantly lower levels of androstenedione (625.3 +/- 168.7 vs 697.0 +/- 211.9 ng/l, P = 0.017) when compared with controls. Multivariate linear regression analysis, adjusted for traditional cardiovascular risk factors, baseline and physiologic characteristics, showed a significant inverse relationship between both serum free testosterone (beta = -0.234, P = 0.028) and androstenedione (beta = -0.241, P = 0.028) levels with the presence of severe atherosclerosis of ICA. CONCLUSIONS: The study provides evidence of a positive association between low serum androgen levels and severe ICA atherosclerosis in postmenopausal women. It suggests that higher, but physiological, levels of androgens in postmenopausal women have a protective role in the development of atherosclerosis of ICA.     

Effects of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein2

Thirty postmenopausal women were randomly treated with desogestrel (DG) or levonorgestrel (LN) 125 micrograms/day for 3 weeks. Desogestrel reduced the serum total and free (non-protein bound) testosterone concentrations. It caused a small decrease in the sex hormone binding globulin capacity (SHBG) but did not influence the free testosterone index (testosterone/SHBG ratio). Levonorgestrel, on the other hand, did not influence the free testosterone concentration, but caused a significant increase in the free testosterone index. Levonorgestrel reduced the HDL and particularly the HDL2 cholesterol concentrations (mean change from 1.75 to 1.45 mmol/l for HDL and from 0.73 to 0.50 mmol/l for HDL2, P less than 0.001). It also caused a reduction in the VLDL triglyceride (P less than 0.05) but not the total serum triglyceride concentration. Desogestrel did not cause any significant changes in HDL or HDL2 cholesterol concentrations, but it reduced the VLDL triglyceride (P less than 0.01) and total serum (P less than 0.05) triglyceride concentrations. Neither of the two progestins influenced the postheparin plasma lipoprotein lipase (LPL) activity or the serum cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT). It is therefore possible that both steroids decreased the hepatic output of triglycerides, which may be clinically important since both progestins are used in combination with ethinylestradiol (EE) which increases the hepatic TG synthesis. The failure of desogestrel to change HDL levels is consistent with earlier data on the lack of effects on HDL by non-androgenic progestins. Levonorgestrel increased the mean activity of postheparin plasma hepatic lipase (HL) from 23.3 to 28.0 mumol X h-1 X ml-1 (P less than 0.05). In contrast, this activity was not influenced by desogestrel. The magnitude of the changes in postheparin plasma HL activity and the free testosterone index (testosterone/SHBG ratio) showed significant positive correlation (+ 0.41, P less than 0.05). On the other hand, the changes in the HDL2 cholesterol and the postheparin plasma HL activity were inversely interrelated (r = 0.52, P less than 0.01). These relationships are consistent with the idea that the effects of different progestins on the HDL cholesterol are mediated by the sex steroid sensitive hepatic endothelial lipase.     

Relationship of high density lipoprotein cholesterol with total and free testosterone and sex hormone binding globulin

A cross-sectional study was performed to see if the previously described association between high density lipoprotein (HDL) cholesterol and plasma total testosterone concentration reflected a relationship with free testosterone or with sex hormone binding globulin (SHBG). In 295 employed middle-aged men, measurements were made of total testosterone and SHBG in serum and of testosterone in saliva, and also of plasma total and HDL cholesterol, plasma triglycerides and other factors which might influence HDL cholesterol levels such as body mass index, alcohol and smoking habits and thyroid hormone levels. In a multiple regression analysis using the GLIM package programme total testosterone concentrations had a persistent positive association with HDL cholesterol (t = 3.5, P less than 0.001) - this association was independent of SHBG (which had a negative association with HDL: t = -1.8, P less than 0.07. The association of HDL cholesterol with testosterone was independent of and stronger than the association of HDL cholesterol with body mass index, alcohol intake and cigarette smoking. Salivary testosterone (a measure of the circulating free hormone) also had a positive independent association with HDL cholesterol. The relationship between HDL cholesterol and testosterone thus appears to reflect an association with circulating hormone levels rather than with the hormone binding globulin.