Fabrizio Ablondi

Aging-related decline of gonadal function in healthy men: correlation with body composition and lipoproteins.

OBJECTIVE: To assess if androgen decline in physiological aging contributes to the concomitant changes in body composition and lipoprotein levels.

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.

Acute changes in circulating hormones in older patients with impaired ventricular function undergoing on-pump coronary artery bypass grafting.

Objectives: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) causes an acute stress response characterized by changes in the levels of several hormones, which might play a role in the high complication rate experienced by older patients after CABG. Thus, the aim of the study was to investigate changes in the circulating levels of anabolic and catabolic hormones in old people undergoing CABG with CPB. Design: Intervention case study. Methods: 19 patients (12 males, 7 females) aged 70.1 ± 6.1 yr (age range 62–80) with coronary artery disease and an ejection fraction <40% who underwent cardiac surgery. Cortisol (Cort), DHEA, DHEAS, LH, estradiol (E2), total testosterone (Te), SHBG, IGF-I were measured the day before, on the day of the procedure and 1, 2, 3, 4, and 30 days after CABG. Results: After surgery, serum IGF-I levels decreased (p<0.001), while levels of Cort, DHEAS and E2 significantly increased in both men and women. Alterations in Te levels differed between the two sexes with a significant decline in men and a significant increment in women. Conclusion: CABG with CPB resulted in a dramatic drop in Te levels in old men and a significant decline in IGF-I in both sexes. Serum Cort levels also significantly increased in both sexes. These hormonal changes may, at least partially, explain why the elderly need prolonged rehabilitation after CABG.

Effects of aging on dehydroepiandrosterone sulfate in relation to fasting insulin levels and body composition assessed by bioimpedance analysis.

Insulin can inhibit dehydroepiandrosterone (DHEA) biosynthesis in humans, as suggested by several studies performed in induced or spontaneous hyperinsulinemia. The increased insulin resistance documented throughout aging, with its accompanying hyperinsulinemia, may contribute to the age-related decline in DHEA synthesis. The aim of this study was to assess if the aging-related differences in DHEA sulfate (DHEA-S) serum levels can be associated with differences in fasting insulin levels, as well as body composition. Two hundred fifty-two healthy subjects of both sexes aged 19 to 90 years with a body mass index (BMI) less than 30 (mean +/- SD, 23.5 +/- 2.4) were studied DHEA-S and insulin serum levels were determined by a radioimmunologic procedure; body composition was assessed by anthropometry (fat mass percentage [FM%] estimated from four skinfold thicknesses by Durnin and Womersley and Siri equations [FM%-SKF]) and by bioimpedance analysis (BIA) (FM% estimated by equations developed by Segal et al and Deurenberg et al for subjects < and > 62 years, respectively [FM%-BIA]). DHEA-S levels were significantly and inversely related to age in both sexes. No significant aging-related differences were found in fasting insulin levels, although a trend toward an increase was apparent in the women on simple regression analysis. No significant associations were found between DHEA-S and insulin levels. As for body composition, a positive relationship to age was apparent for FM%-SKF, FM%-BIA, and waist to hip ratio (WHR), whereas BMI and phase angle ([PA] a bioelectric parameter considered an index of the ratio between intracellular and extracellular water) were inversely related to age. Fasting insulin levels were positively related to FM% as estimated by both BIA and anthropometry, independently of age in both sexes; in addition, a positive correlation with WHR and with the subscapular to triceps skinfold thickness ratio (SS/TS) was found in men and women, respectively. No significant correlation was apparent between DHEA-S and body composition indices in men, whereas in women a slight negative correlation between DHEA-S and WHR was documented, and was still significant after adjustment for age and fasting insulin. Stepwise multiple regression analysis confirmed that DHEA-S levels are not related to fasting insulin, but are independently related to age and, in women only, to WHR. Our study suggests that the DHEA-S decline due to aging is independent of fasting insulin, at least in healthy, non-obese people. In addition, it is not related to the aging-dependent changes in body composition in terms of FM% and fat-free mass (FFM) percentage (FFM%). Only in women could changes in fat distribution be slightly associated with DHEA-S decline, although such a relation cannot be accounted for by changes in insulin levels.

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 (β±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 (β±SE: 36.7±12.2, p=0.003). The association was still significant when IL-6 was introduced in the model (β±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.

Magnesium and anabolic hormones in older men

Optimal nutritional and hormonal statuses are determinants of successful ageing. The age associated decline in anabolic hormones such as testosterone and insulin-like growth factor 1 (IGF-1) is a strong predictor of metabolic syndrome, diabetes and mortality in older men. Studies have shown that magnesium intake affects the secretion of total IGF-1 and increase testosterone bioactivity. This observation suggests that magnesium can be a modulator of the anabolic/catabolic equilibrium disrupted in the elderly people. However, the relationship between magnesium and anabolic hormones in men has not been investigated. We evaluated 399 ≥65-year-old men of CHIANTI in a study population representative of two municipalities of Tuscany (Italy) with complete data on testosterone, total IGF-1, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS) and serum magnesium levels. Linear regression models were used to test the relationship between magnesium and testosterone and IGF-1. Mean age of the population was 74.18 ± 6.43 (years ± SD, age range 65.2-92.4). After adjusting for age, magnesium was positively associated with total testosterone (β ± SE, 34.9 ± 10.3; p = 0.001) and with total IGF-1 (β ± SE, 15.9 ± 4.8; p = 0.001). After further adjustment for body mass index (BMI), log (IL-6), log (DHEAS), log (SHBG), log (insulin), total IGF-1, grip strength, Parkinsons disease and chronic heart failure, the relationship between magnesium and total testosterone remained strong and highly significant (β ± SE, 48.72 ± 12.61; p = 0.001). In the multivariate analysis adjusted for age, BMI, log (IL-6), liver function, energy intake, log (insulin), log (DHEAS), selenium, magnesium levels were also still significantly associated with IGF-1 (β ± SE, 16.43 ± 4.90; p = 0.001) and remained significant after adjusting for total testosterone (β ± SE, 14.4 ± 4.9; p = 0.01). In a cohort of older men, magnesium levels are strongly and independently associated with the anabolic hormones testosterone and IGF-1.

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.

Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH)

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.

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.

Evaluation of the circadian profile of peripheral plasma galanin concentrations in normal subjects

Galanin administration can influence pituitary function principally resulting in an increase in GH secretion. However, the role of circulating GAL levels in human endocrine function is still unknown. In the present study we simultaneously measured the circadian profiles of GAL, ACTH and GH in peripheral blood of ten adult subjects. Plasma samples were collected through an intravenous catheter at 0800, 1200, 1600, 2000, 2200, 2400, 0200, 0400 hours. The results were statistically evaluated by the cosinor analysis technique. A significant circadian rhythm of both plasma ACTH (p < 0.001) and GH levels (p < 0.03) was found with acrophases occurring at 0753 hrs and 0131 hrs for ACTH and GH, respectively. On the contrary, no significant rhythm was found in plasma GAL levels, indicating that no correlations exist between GAL and either GH or ACTH circadian profiles. Furthermore, the simultaneous assay of both GAL and GH plasma levels during a nocturnal frequent sampling performed in four volunteers showed the presence of peaks in GAL levels which, however, were not concomitant to the peaks in GH levels. These data demonstrate the lack of rhythmicity in the circadian profile of plasma GAL levels in healthy human subjects. The role of GAL in human endocrine function remains unknown and these results suggest that, in spite of the well documented increase in plasma GH concentrations following the intravenous administration of GAL, physiologically circulating levels of GAL are likely not involved in the regulation of GH secretion.