SHBG, sex hormones, and inflammatory markers in older women.

CONTEXT: In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. OBJECTIVE: The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. DESIGN AND PATIENTS: We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-α. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. RESULTS: In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 ± 0.08; P = 0.006) and E2 (0.21 ± 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. CONCLUSION: In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state.

Association of plasma selenium concentrations with total IGF-1 among older community-dwelling adults: the InCHIANTI study.

BACKGROUND & AIMS: Insulin-like growth factor (IGF-1) stimulates cell proliferation and inhibits cell apoptosis. Recent studies underline its importance as anabolic hormone and nutritional marker in older individuals. IGF-1 synthesis and bioactivity are modulated by nutritional factors including selenium intake. However, whether circulating IGF-1 levels are positively influenced by plasma selenium, one of the most important human antioxidants, is still unknown. METHODS: Selenium and total IGF-1 were measured in 951 men and women ≥ 65 years from the InCHIANTI study, Tuscany, Italy. RESULTS: Means (SD) of plasma selenium and total IGF-1 were 0.95 (0.15) µmol/L and 113.4 (31.2)ng/mL, respectively. After adjustment for age and sex, selenium levels were positively associated with total IGF-1 (ß±SE: 43.76±11.2, p=0.0001). After further adjustment for total energy and alcohol intake, serum alanine aminotransferase (ALT), congestive heart failure, selenium remained significantly associated with IGF-1 (ß±SE: 36.7±12.2, p=0.003). The association was still significant when IL-6 was introduced in the model (ß±SE: 40.1±12.0, p=0.0008). CONCLUSIONS: We found an independent, positive and significant association between selenium and IGF-1 serum levels in community dwelling older adults.

A one-year follow-up on the effects of raloxifene on thyroid function in postmenopausal women.

OBJECTIVE: Estrogens increase serum thyroxine-binding globulin (TBG) and total thyroxine (TT4) concentrations. Serum free thyroxine (FT4) concentrations, however, remain normal. Raloxifene (RAL) is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. Data on the long-term effects of RAL on thyroid physiology are scanty. We evaluated the effects of RAL administration for 1 year on thyroid function in osteopenic, postmenopausal women. DESIGN: Fifty osteopenic, postmenopausal women were randomly assigned to receive either RAL (60 mg/day, n = 25) or placebo (PL, n = 25) for 1 year, in a double-blind study. Measurements of serum TBG, TT4, FT4, thyroid-stimulating hormone (TSH), thyroid hormone-binding ratio (THBR), FT4 index (FT4-I) and TT4/TBG ratio were carried out at baseline and after 4 and 12 months of therapy. RESULTS: Baseline values were similar in both treatment groups. Serum TBG concentrations were increased during RAL treatment from baseline values of 29.60 +/- 0.9 microg/mL to 31.45 +/- 1.33 and 32.34 +/- 1.37 microg/mL at 4 months and 1 year, respectively (P < 0.05, baseline v 1-year values) but were unchanged during PL treatment. A small, insignificant increase in TT4 and TSH concentrations occurred in the RAL group and no changes in the PL group. All other values were unchanged during either treatment. CONCLUSIONS: These results demonstrate that RAL significantly increased serum TBG levels, but the changes were small and not accompanied by changes in FT4-I, FT4, or TSH concentrations, suggesting that long-term RAL treatment is unlikely to clinically affect the thyroid status in euthyroid, postmenopausal women.

The role of lipid profile in determining the risk of ischemic stroke in the elderly: a case-control study.

In this study, we investigated the association of lipids with ischemic stroke and its different subtypes in elderly patients. In particular, lipid parameters not extensively investigated so far in previous case-control studies specifically focused in the old population, such as lipoprotein Lp (a) and Apoproteins AI (ApoAI) and B (ApoB), have been taken into account. Seventy nine patients (mean age 83 +/- 7.4, range 67-99), consecutively admitted to a Geriatric Ward between January 1998 and June 2000 with acute stroke (first event) were studied. A complete clinical and laboratory assessment, including neurological evaluation, head CT scan, carotid ultrasonography and ECG, was employed to define the clinical and etiologic stroke subtype, according to standardized criteria. Fasting blood samples were collected within 48 h from admission, for determination of total cholesterol (TC), triglycerides (TG), High Density Lipoprotein-cholesterol (HDL-C), Lp(a), ApoAI and ApoB; Low Density Lipoprotein-Cholesterol (LDL-C) was estimated by Friedwald formula. Eighty eight age and sex-matched outpatients, referred to the hospital for non-inflammatory disorders of joints and musculoskeletal system, served as controls. Patients showed HDL-C and HDL-C/ApoAI ratio significantly lower than controls, with higher LDL-C/HDL-C ratio. Analysis on quartiles of lipoprotein concentrations showed also a significant increase in odds of stroke for LDL-C concentrations over 100 mg/dl, in absence of a linear relationship between LDL-C levels and risk. Multiple logistic regression, adjusting for non-lipid risk factors for stroke, confirmed the independent association of low HDL-C and HDL-C/ApoAI with all strokes, as well as with each subtype. In conclusion, these data suggest that lipids give some contribution to stroke risk even in the elderly, with a more prevalent role for HDL than LDL, and that lipid profile assessment must be taken into account in estimating the individual risk of stroke.

Effects of raloxifene on carotid blood flow resistance and endothelium-dependent vasodilation in postmenopausal women.

Raloxifene is one of the most important selective estrogen receptor modulators currently employed for the treatment of postmenopausal osteoporosis. However, it has also been suggested that this compound affects the vascular system. We evaluated both carotid blood flow resistance and endothelium-dependent vasodilation in 50 healthy postmenopausal women randomly assigned to receive, in a double blind design, either raloxifene (60 mg per day; N=25 subjects) or placebo (N=25 subjects) for 4 months. Indices of carotid blood flow resistance, such as the pulsatility index (PI) and resistance index (RI), as well as the flow-mediated brachial artery dilation were measured both at baseline and at the end of treatment. Changes in PI were -1.86+/-2.24 and -2.15+/-2.22% after placebo and raloxifene treatment, respectively, with no significant differences between groups. Changes in RI were -0.77+/-1.72 and -1.81+/-1.54% after placebo and raloxifene treatment, respectively, with no significant differences between groups. At the end of the treatment period, the increments in artery diameter measured after the flow stimulus were 10.79+/-2.39 and 6.70+/-1.23% for placebo and raloxifene, respectively, with no significant differences between groups. These results demonstrate no significant effects of raloxifene on either carotid blood flow resistance or brachial artery flow-mediated dilation in postmenopausal women.