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Biomedical subjects

L Denti

Publications and source records attributed to L Denti.

At least 19 recordsLinked to original sources

The PADAM syndrome and its clinical manifestations: the muscle mass.

Many animal and in vitro studies suggest that testosterone can affect body composition. Therefore, the age-related decline in testosterone (T) likely contributes to the concomitant decrease in lean mass documented in men. While observational data in humans are not conclusive, intervention studies suggest that aged men could benefit from T replacement in term of muscle mass preservation. However, its potential positive impact on strength and functional status is unproven.

Aged↗

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.

Aged↗

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. DESIGN: Cross-sectional, observational study. SETTING: A university-based outpatient center. SUBJECTS: The study comprised 206 healthy volunteers (aged 18-95 years). MEASUREMENTS: Blood samples were drawn after an overnight fast for the assay of hormones (free testosterone (FT), estradiol (E2), and sex hormone-binding globulin (SHBG)) and lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and lipoprotein Lp(a)). At the same time, body composition was assessed by both anthropometry (fat mass percentage (FM%) estimated from four measures of skinfold thickness using the Durnin and Womersley equation and the Siri equation) and by bioimpedance analysis (FM% estimated using the Segal or Deurenberg equations, respectively, for subjects younger or older than 62 years). RESULTS: A significant age-related decline was found for FT and E2 concentrations, whereas SHBG levels were related positively with age. No significant association was apparent between hormonal changes and the concomitant modifications of body composition and lipoproteins. Only SHBG showed a significant inverse association between FM% and the waist-to-hip ratio, independent of age. The comparison between older hypogonadal (with FT levels below the lower limit of the normality range assessed in younger subjects) and eugonadal men did not show any significant differences in body composition or lipid profile. CONCLUSIONS: This study suggests that, in men, androgen decline caused by normal aging does not significantly affect some targets of testosterone action, such as body composition and lipid metabolism. Therefore, androgen supplementation in hypogonadal older men cannot be expected to influence nutritional status and body composition to the same extent that it does other main targets of testosterone action, such as sexual activity and muscle strength. However, we cannot exclude that selected subsets of older patients with low testosterone levels, especially if affected by catabolic disease, could benefit from the effects of androgen administration on nutritional status.

Adolescent↗

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.

Adolescent↗

Effects of androgen suppression by gonadotropin-releasing hormone agonist and flutamide on lipid metabolism in men with prostate cancer: focus on lipoprotein(a).

No clear relation between lipoprotein(a) [Lp(a)] and endogenous gonadal hormones has been demonstrated. In this study, we compared the effects on Lp(a) of pharmacological castration in 50 patients with prostate cancer who were undergoing therapy with a gonadotropin-releasing hormone agonist (goserelin), with effects on 58 age-matched controls. We also studied 16 untreated patients under baseline conditions and after 3 months of therapy with goserelin alone or combined with an antiandrogen (flutamide). Neither cross-sectional nor prospective studies showed any significant effects of therapy on Lp(a). However, cluster analysis identified a subgroup of patients showing slight but significant increases in Lp(a) concentrations, as well as greater declines of testosterone and estradiol, suggesting that androgen, like estrogen, can exert some slight, though not easily detectable, influence on Lp(a).

Aged↗

Lipoprotein Lp(a) and cerebrovascular disease in the elderly: correlations with the severity of extracranial carotid atherosclerosis assessed by ultrasonography.

High levels of lipoprotein Lp(a) are related to cerebrovascular disease clinical manifestations, as well as to the severity of extracranial carotid atherosclerosis assessed by ultrasonography. In order to investigate the relationship of Lp(a) to the severity of carotid atherosclerosis in the elderly, 100 subjects, aged 78.5 +/- 0.6 yrs underwent an echo-color-doppler scanning of carotids; atherosclerosis severity, assessed as maximum percentage stenosis, presence of complicated plaque and Intima-Media Thickness (IMT), was related to Lp(a) levels, assayed by an immunoenzymatic procedure. A slight association between Lp(a) and CVD clinical manifestations was apparent only in subjects under 78 yrs and for Lp(a) values above 25 mg/dL. Lp(a) levels were not related either to the degree of stenosis, the presence of complicated plaque, or IMT. As for other selected risk factors, while no relationship was found for clinical CVD and IMT, the maximum percentage of stenosis and the presence of complicated plaques were positively related to LDL-cholesterol in subjects under 78 yrs. We can conclude that Lp(a), albeit unrelated to the severity of extracranial vessel atherosclerosis, maintains a role as cerebrovascular risk factor in the elderly, being slightly related to clinical manifestations; however its discriminant power is lower than in middle-aged people and further decreases throughout ageing.

Aged↗

Correlation between plasma lipoprotein Lp(a) and sex hormone concentrations: a cross-sectional study in healthy males.

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.

Adult↗

alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects.

Growth hormone (GH) secretion is decreased during aging in humans and in rodents. This decrease may be due to increased hypothalamic somatostatin release, which is inhibited by cholinergic agonists, or to decreased secretion of GHRH. Alpha-glyceryl-phosphorylcholine (alpha-GFC) is a putative acetylcholine precursor used in the treatment of cognitive disorders in the elderly. In order to learn what effect alpha-GFC had on GH secretion, GH-release hormone (GHRH) was given to young and old human volunteers, with or without the addition of alpha-GFC. GH secretion was greater in the younger subjects than in the old individuals, and both groups had a greater GH response to the GHRH+alpha-GFC than to GHRH alone. The potentiating effect of alpha-GFC on GH secretion was more pronounced in the elderly subjects. These findings confirm the observation that aged individuals respond less well to GHRH than younger subjects, and provides further evidence that increased cholinergic tone enhances GH release.

Adult↗

The effects of aging on the secretion of the common alpha-subunit of the glycoprotein hormones in men.

To investigate the effects of aging on the secretion of the common alpha-subunit of the glycoprotein hormones, we measured basal levels of luteinizing hormone (LH), testosterone (T) and alpha-subunit in 176 normal men aged 19 to 89 years. In addition, in two groups of young (less than 65 years; n = 25) and old (greater than 65 years; n = 15) subjects, the effects of luteinizing hormone-releasing hormone (LHRH) on LH and alpha-subunit secretion were determined. Age-related increases in serum alpha-subunit and LH were noted only in the oldest men while T levels decreased progressively with advancing age. LHRH stimulation resulted in significantly greater secretion of alpha-subunit in the old subjects while no difference in LH release between young and old men was observed. Moreover, there was a delay to peak LH and alpha-subunit levels after LHRH in the old subjects. These data suggest that the aging process in males involves deficits in both testicular and gonadotroph functions as demonstrated by (1) the relative hypogonadotropic hypogonadism seen until the ninth decade; (2) the hypergonadotropic hypogonadism apparent in men greater than 80 years; (3) the delay in the timing of peak responses of LH and alpha-subunit after LHRH administration; and (4) the disproportionate increase in the secretion of alpha subunit relative to intact LH.

Adult↗

Effects of cytidine 5'-diphosphocholine administration on basal and growth hormone-releasing hormone-induced growth hormone secretion in elderly subjects.

The basal and GH-releasing hormone-stimulated secretion of GH declines in the elderly. We tested the ability of cytidine 5'-diphosphocholine, a drug used in the treatment of stroke and Parkinson's disease, to alter GH secretion in 11 healthy elderly volunteers, aged 69-84. Each subject received an iv infusion of 2 g of cytidine 5'-diphosphocholine or normal saline. GHRH and TRH were also administered during cytidine 5'-diphosphocholine infusions. The infusion of cytidine 5'-diphosphocholine induced a 4-fold (p less than 0.05) increase in serum GH levels over basal values. A small increase in GH was seen after GHRH administration. However, the addition of GHRH to the cytidine 5'-diphosphocholine infusion resulted in a GH response which was significantly greater than that seen after GHRH alone; the integrated concentration of GH was more than 2-fold greater in the cytidine 5'-diphosphocholine treated group (706.85 +/- 185.1 vs 248.9 +/- 61.4 micrograms.l-1.(120 min)-1; p = 0.01). The PRL and TSH responses to TRH were not significantly affected by cytidine 5'-diphosphocholine infusion, indicating that dopaminergic mechanisms are not involved. These studies demonstrate that cytidine 5'-diphosphocholine can enhance basal and GHRH-stimulated GH release in the elderly, but the mechanism of action of the drug remains unclear.

Aged↗

Dissociated effect of buserelin on luteinizing hormone (LH) and alpha subunit in men.

Chronic treatment with LHRH analogs is known to depress testosterone (T) values to castration levels. In contrast to results from animal experiments, studies in humans indicate that a pituitary-dependent mechanism predominates in the suppression of plasma T. However, this reduction in T levels may occur when LH values are within or below the normal range. One explanation for this result has been that while absolute values of LH in serum may not change, the bioactivity of LH is reduced. The present study has been performed to determine whether this discrepancy between LH and T values is obscured by the hypersecretion of the alpha-subunit which is devoid of any biological activity but crossreacts in most RIAs with LH. Following 2 days of blood collection to establish basal serum hormone levels, six men with prostatic cancer were treated with the LHRH agonist, Buserelin (500 micrograms sc, daily injection) for 15 days. The most significant endocrine responses at the end of this treatment were as follows: 1) T levels were depressed to the castration range; 2) no change was seen in the LH values with a conventional RIA procedure which crossreacted with the alpha-subunit; 3) a significant decrease was found in the LH values evaluated with an immunoradiometric (IRMA) method, which shows no cross-reactivity with the alpha-subunit; 4) there was a significant increase in the alpha-subunit levels; and 5) serum FSH levels were significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Secretion of alpha-subunit and intact gonadotropins after surgical and chemical castration.

In order to investigate the regulatory mechanisms involved in the secretion of glycoprotein hormones, we studied the secretory patterns of LH, FSH and alpha-subunit in hypogonadal men. Three groups of patients with carcinoma of the prostate were studied both before and 15 days after orchiectomy, or the initiation of ketoconazole or LHRH analog therapy. There were significant increases (P less than 0.01) in LH and alpha-subunit levels in the patients treated with orchiectomy and ketoconazole, but FSH levels increased only in the orchiectomized patients. After LHRH analog treatment, LH levels were significantly decreased when assayed with an immunoradiometric assay method which does not cross-react with alpha-subunit. FSH values were significantly lower than pretreatment levels, while alpha-subunit levels remained significantly elevated throughout the study period. These results demonstrate that after both chemical (ketoconazole) and surgical castration, the secretion of alpha subunit follows a pattern which is tightly correlated with that of LH but not of FSH. However, after LHRH analog treatment, alpha-subunit appears to be the sole secretory product of the gonadotroph.

Aged↗