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Biomedical subjects

V Vicennati

Publications and source records attributed to V Vicennati.

30 records · Page 2Linked to original sources
PubMed1998

Secretion of major adrenal androgens following ACTH administration in obese women with different body fat distribution.

To investigate whether obese female subjects with abdominal obesity may have adrenal androgen hypersecretion, we examined two groups of women with abdominal (n = 12) and peripheral (n = 13) obesity (defined by body mass index and waist-to-hip ratio) and a group of seven healthy normal-weight women. All subjects underwent the following protocol study that included a) baseline determination of major adrenal androgens, b) an ACTH test, performed by administering two boli of ACTH (Synacthen, 0.2 microg/Kg BW, e.v.), at 90 min intervals, with blood samples taken for cortisol and androgens, c) an oral glucose tolerance test, performed by administering glucose (75 gr), with blood samples taken for glucose and insulin determination. Each woman also underwent a control saline study. We then investigated the relationships between basal and stimulated androgen levels, body weight and fat distribution and fasting and stimulated insulin levels. Although basal cortisol levels were similar, their increase (as AUC) after the ACTH test was higher in women with abdominal obesity than in the other groups. On the contrary, there were no significant differences in basal and stimulated serum levels of dehydroepiandrosterone, androstenedione and 17-hydroxyprogesterone among the three groups. Fasting and stimulated (as AUC) insulin levels were significantly higher (p < 0.05) in women with abdominal obesity than in those with peripheral obesity and controls. No significant correlation was present between basal and stimulated androgen levels and body mass index, the waist-to-hip ratio or basal and stimulated cortisol values. Therefore, our data indicate that adrenal androgen secretion following low-dose ACTH administration in premenopausal women does not seem to be a function of body fat mass, fat distribution and insulin levels, nor does it correlate with the capacity of the adrenal glands to secrete cortisol in both basal and stimulated conditions.

17-alpha-Hydroxyprogesterone↗
PubMed1998

[Influence of weight and distribution of adipose tissue in functional hyperandrogenism].

Approximately half the women with the polycystic ovary syndrome (PCOS) are obese or overweight. Obesity and body fat distribution have independent roles in the development of hyperandrogenism in PCOS. Most obese and normal weight PCOS are insulin resistant and hyperinsulinemic. Moreover, a significant positive correlation exists between the degree of hyperandrogenism and that of hyperinsulinism. The pathogenetic role of obesity may involve different mechanisms, the major one being the hyperinsulemic state, since insulin is capable of stimulating ovarian androgen secretion and controlling androgen metabolism and transport in peripheral tissues. Abdominal body fat distribution in obese women with PCOS amplifies the degree of hyperandrogenism and related clinical symptoms and signs. Both loss of body weight and/or the reduction of the degree of hyperinsuliemia, induced by diet or insulin-sensitizing drugs, have important effects, since they reduce blood androgen levels and can improve ovulation and clinical signs of hyperandrogenism.

Adipose Tissue↗
PubMed1997

Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Virgilio-Menopause-Health Group.

In women, sex hormone-binding globulin (SHBG) concentrations are the result of a balanced effect of stimulatory and inhibitory factors. Estrogens represent the principal stimulatory hormones, whereas androgens, insulin, excess body fat, and the pattern of body fat distribution have inhibitory effects. Menopause is characterized by major changes in blood sex steroid concentrations, notably a marked reduction of estradiol levels. In this study, we therefore investigated the relationship between hormonal and nonhormonal regulatory factors of SHBG and its blood levels in two groups of premenopausal and postmenopausal women characterized by normal-high or reduced estrogen concentrations. The data were obtained from an analysis of the cross-sectional database obtained during the first survey of the Virgilio-Menopause-Health Project, an epidemiologic longitudinal study aimed at investigating the impact of menopause on body weight, fat distribution, and related major metabolic, hormonal, and cardiovascular risk factors. A total of 329 women, 133 in premenopause and 196 in postmenopause without diabetes, thyroid diseases, or relevant cardiovascular, renal, and hepatic dysfunction, were included in the study. A clinical history (including dietary and physical-activity habits), anthropometry (body mass index [BMI], waist to hip ratio [WHR], and bioelectrical impedance analysis [BIA]), and morning blood samples in the fasting state for sex hormones, insulin, and biochemistry were available for all the women. Premenopausal and postmenopausal women showed no significant difference in SHBG concentrations (38.7 +/- 17.9 v 36.6 +/- 17.5 nmol/L, respectively). On the contrary, postmenopausal women were characterized by a marked reduction of estradiol levels and significantly lower levels of testosterone. After adjusting for age, insulin was lower and the glucose to insulin ratio was higher in postmenopause than in premenopause. Age-adjusted values for all anthropometric parameters were not significantly different in the two groups. In simple correlation models, SHBG was significantly and negatively correlated with BMI, WHR, and insulin and testosterone levels in both premenopausal and postmenopausal women, whereas estradiol levels correlated positively and significantly with SHBG only in the premenopausal group. A significant positive correlation between the glucose to insulin ratio and SHBG was present in both groups. Using multiple regression models, in the premenopausal group, SHBG levels were correlated positively with estradiol and negatively with testosterone and insulin, but not with the WHR. On the contrary, in the postmenopausal group, SHBG values had a significant negative correlation with the WHR, whereas the relationship with estradiol was not significant; moreover, the relationship with testosterone and insulin, although significant, became less marked. In conclusion, this study indicates that (1) there is no significant difference in SHBG blood concentrations between premenopause and postmenopause; (2) SHBG values are correlated positively with estradiol and negatively with insulin and testosterone concentrations, but the predictive value of these variabiles on SHBG appears to be different in premenopause and postmenopause; and (3) SHBG levels decrease with increasing WHRs, particularly in the postmenopausal group. Therefore, determinants of SHBG blood concentrations are likely to change on passing from premenopausal to postmenopausal status. In particular, there seems to be a threshold level for which estradiol is an important determinant of SHBG blood concentrations.

Adult↗
PubMed1997

Effects of acute hyperinsulinemia on testosterone serum concentrations in adult obese and normal-weight men.

In a previous study performed in adult obese and normal-weight male subjects, we found that suppression of insulin levels by diazoxide reduced testosterone and increased sex hormone-binding globulin (SHBG) blood concentrations. These and other data suggested that insulin may have a regulatory capacity in testosterone secretion and/or metabolism in men, similar to what has already been demonstrated in women. In this study, we investigated the effects of acute hyperinsulinemia on major androgen levels, including testosterone, in two groups of normal-weight in = 11) and obese (n = 9) men. Acute hyperinsulinemia was obtained by the euglycemic-hyperinsulinemic clamp technique. Relationships between the degree of insulin resistance (ie, total glucose disposal [M value]) and testosterone levels were also evaluated. Basal testosterone levels in obese subjects (10.40 +/- 3.02 nmol/L) were significantly lower than in normal-weight controls (15.50 +/- 4.65 nmol/L, P < .01), whereas no difference was present in androstenedione and dehydroepiandrosterone sulfate (DHEA-S) concentrations. During the clamp study, testosterone was significantly increased in the obese group (11.79 +/- 3.64 nmol/L, P < .05) but not in the control group (15.81 +/- 4.54 nmol/L, P = NS). The other two androgens did not significantly change in either the obese or control group. There was a highly significant correlation between baseline testosterone concentrations, with M values suggesting a relationship between impaired peripheral insulin sensitivity and reduced plasma testosterone concentrations. It should be pointed out that there was a certain discrepancy in the testosterone variations, particularly in the control group, in which two thirds of the subjects had no change or some decrease in testosterone levels, whereas in the remainder testosterone increased over the values of the assay variation coefficient. These findings are consistent with the hypothesis that insulin may regulate testosterone blood levels also in male subjects. Whether these effects are primarily due to increased hormone secretion or reduced clearance needs to be investigated.

Acute Disease↗
PubMed1997

Achievement of near-normal body weight as the prerequisite to normalize sex hormone-binding globulin concentrations in massively obese men.

OBJECTIVE: To investigate the effects of weight loss on sex hormone-binding globulin (SHBG) in massively obese males and whether normal SHBG concentrations could be obtained regardless or not of the achievement of normal body weight values. DESIGN AND SUBJECTS: Sera were collected for SHBG determination from 63 massively obese men, partly before they underwent biliopancreatic diversion (pre-op group = 11) and partly during the post-surgical follow up (post-op group = 52), and twenty normal weight healthy control men. MEASUREMENTS: Serum SHBG was measured using a noncompetitive liquid-phase immunoradiometric assay. RESULTS: Baseline general characteristics were similar in both obese groups. Obese patients in the post-op group had lost 46.4 +/- 2.9 kg since they had undergone operation, namely during a mean period of 14.9 +/- 13.8 (range 1-58) months follow up. Obese groups had significantly lower SHBG than normal weight controls (66.2 +/- 18.6 nmol/l). However, pre-op obese (19.9 +/- 5.5 nmol/l) had significantly lower values than post-op obese subjects (45.5 +/- 24.8 nmol/l; P < 0.001). There were a highly significant correlation between SHBG and individual BMI values (r = -0.629; P < 0.001). Moreover, the post-op obese with BMI values lower or equal to 28 had significantly higher SHBG concentrations than those with BMI greater than 28 (62.8 +/- 22.2 nmol/l vs 32.1 +/- 19.6 nmol/l; P < 0.001), but not significantly different with respect to normal weight controls. CONCLUSIONS: Massively obese men weight loss can completely reverse SHBG abnormalities, which can be restored to the normal range when near-normal body weight is achieved. Since reduced SHBG concentrations can be an independent risk factor for the development of diabetes and cardiovascular disease, this represents an additional benefit of weight loss program in massively obese individuals.

Adult↗
PubMed1997

Leptin and the hypothalamic-pituitary-adrenal axis activity in women with different obesity phenotypes.

OBJECTIVE: Women with visceral obesity may have hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Since glucocorticoids are involved in the expression of the ob gene, this study was carried out to investigate the relationship between serum leptin and the activity of the HPA axis in women with different obesity phenotypes. DESIGN: Cross sectional clinical study. SUBJECTS: Fifteen obese (Body Mass Index BM128 kg/m2) women and ten normal weight control women (BM126 kg/m2) were included in the study. MEASUREMENTS: Body fat distribution was defined by CT scan at the L4-L5 level. Baseline blood samples were obtained for hormone concentrations. The activity of the HPA axis was evaluated by measuring ACTH and cortisol blood levels after combined iv administration of corticotropin releasing factor (100 microg) + arginine-vasopressin (0.3 IU). RESULTS: Baseline cortisol, ACTH, and androgen levels were similar in all groups, whereas leptin levels were significantly higher in the obese groups than in normal weight controls, without any significant difference between women with different obesity phenotypes. Incremental areas of ACTH and cortisol were significantly higher in women with visceral obesity than in those with subcutaneous obesity and controls. No significant correlation was found between the activity of the HPA axis and leptin concentrations. Leptin showed a highly significant correlation with BMI and subcutaneous fat and a weak but significant correlation with visceral fat and the visceral-to-subcutaneous fat ratio. CONCLUSION: Women with different obesity phenotypes had similar serum leptin concentrations but different HPA axis activity, and there was no correlation between them.

Adrenocorticotropic Hormone↗
PubMed1997

Influence of menopause on blood cholesterol levels in women: the role of body composition, fat distribution and hormonal milieu. Virgilio Menopause Health Group.

OBJECTIVES: In this study we investigated the relationships between blood lipids and menopausal status. SETTING AND SUBJECTS: All data were obtained from the first cross-sectional examination of the Virgilio Menopause Health Project in a large cohort of middle-aged women in pre, peri-, and postmenopausal age. The data refer to 426 women without metabolic or endocrine diseases, relevant hepatic, renal and cardiovascular abnormalities, none were dieting or taking medications. MAIN OUTCOME MEASURES: A precoded questionnaire including full clinical history, socio-economic and personal information, habitual diet, physical activity, drug use and smoking habits, careful recording of gynaecological events and family history for disease was completed. Several anthropometric parameters and the bioelectrical impedance analysis was used to measure free fatty mass. Blood samples for hormones and biochemistry were also obtained. RESULTS: There were no significant differences on body mass index, fatty mass, free fatty mass and parameters of body fat distribution between the three groups. Again, there were no differences in smoking habits, dietary intake or indices of physical activity amongst the groups. There was a significant increase from pre to postmenopause of LH and FSH and a decrease of oestradiol and testosterone, whereas no difference was found in sex hormone-binding globulin. Age-adjusted values of glucose, triglycerides and high density lipoprotein (HDL-) cholesterol were similar in all groups, whereas postmenopausal women had significantly higher values of total and low density lipoprotein (LDL-) cholesterol. On the contrary, there was a significant fall in insulin levels passing from pre to postmenopause. In multiple regression models, total and LDL-cholesterol correlated positively with body mass index, waist-to-hip ratio and age, and negatively with free fatty mass and oestradiol blood levels. CONCLUSIONS: These results are consistent with the hypothesis that menopausal status may have a significant and independent effect in determining increased total and LDL-cholesterol concentrations in postmenopausal women.

Adipose Tissue↗
PubMed1997

Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome.

Obesity may be an important pathogenetic factor involved in the development of hyper-androgenism in women with polycystic ovary syndrome (PCOS). Among several other mechanisms, hyperinsulinaemia plays a fundamental role, due to its gonadotrophic function, which has been demonstrated both in vitro and in vivo. Therefore, not surprisingly, weight loss may be expected to have several beneficial effects upon clinical, endocrinological and metabolic features of obese women presenting both PCOS. In particular, weight loss appears to be associated with a significant improvement in menses abnormalities, ovulation and fertility rates, and with a reduction of hyperandrogenism, hyperinsulinaemia, and altered gonadotrophin pulsatile secretion. The central role of improved insulin concentrations and insulin-resistant state is emphasized by the fact that similar effects can be achieved by both short- and long-term administration of metformin, an insulin-lowering drug which ameliorates peripheral insulin action in non-diabetic insulin resistant states. We therefore recommend weight loss as a first-line therapeutic option in all women with obesity and PCOS.

Female↗
PubMed1996

Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in women with visceral and subcutaneous obesity: effects of the corticotropin-releasing factor/arginine-vasopressin test and of stress.

In a previous study, we demonstrated that premenopausal women with visceral obesity have hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by an exaggerated hormone response to corticotropin-releasing factor (CRF) and corticotropin (ACTH) stimulation. The hypothalamic peptide flow that stimulates the pituitary, particularly after a physiological stress challenge, involves not only CRF, but also arginine-vasopressin (AVP), which synergizes the CRF capacity to stimulate pituitary hormone secretion. Previous studies in humans have demonstrated that combining AVP with CRF permits maximal stimulation of the pituitary, providing a more appropriate method of assessing pituitary hormone reserve. We therefore investigated the response of the HPA axis to combined CRF and AVP stimuli in obese women with different obesity phenotypes. Moreover, we examined hormonal and cardiovascular responses to several mental stress tasks, according to previously standardized procedures. Two groups of age-matched premenopausal eumenorrheic obese women with visceral (V-BFD) or subcutaneous (S-BFD) body fat distribution and a group of normal-weight healthy controls were investigated. All women randomly underwent the following protocol: (1) a combined CRF/AVP test (100 micrograms plus 0.3 IU intravenously [IV], respectively); (2) a standardized stress test, which consisted of completing two puzzles and a mental arithmetic test; and (3) a control saline test. Blood samples for ACTH and cortisol determinations were obtained before and during each test, and measurements of arterial blood pressure and pulse rate were made at regular intervals during the stress test. After combined CRF/AVP administration, ACTH and cortisol were significantly higher in V-BFD than in the other two groups. In contrast, no significant hormonal variation was found in either group during stress tasks. During the stress test, pulse rate (but not arterial blood pressure) significantly increased after 8 and 15 minutes in the V-BFD group, whereas no significant variation was found in S-BFD and control women. A significant correlation was present between the pulse rate and change in cortisol level during the stress test at minutes 8 (r=.54, P<.05) and 15 (r=.57, p<.01) in all women considered together. Subjective emotional involvement during stressful tasks was measured by a two-dimensional short verbal scale, which revealed that the stress section had a more significant impact in obese V-BFD than in S-BFD and control women. These data therefore confirm that women with visceral obesity have hyperactivity of the HPA axis, and that the combined CRF/AVP stimulation may offer a good tool for investigating pituitary reserve in this obesity phenotype. Moreover, the results indicate that these women probably have a hyperreactive sympathetic response to acute stress that seems interrelated to that of the HPA axis.

Adrenocorticotropic Hormone↗
PubMed1995

Nitrendipine treatment in women with polycystic ovarian syndrome: evidence for a lack of effects of calcium channel blockers on insulin, androgens, and sex hormone-binding globulin.

It has been shown that in vitro calcium channel blockers may regulate insulin secretion, and in vivo studies have demonstrated that they can reduce the degree of hyperinsulinemia and ameliorate the insulin-resistant state in subjects (particularly men) with obesity and hypertension. It is also commonly accepted that hyperinsulinemia may be an important factor responsible for the development of hyperandrogenism in obese women with polycystic ovarian syndrome (PCOS). We, therefore, investigated whether the administration of nitrendipine, a widely used calcium channel blocker, may improve both insulin levels and hyperandrogenism in a group of seven insulin-resistant hyperinsulinemic women with obesity and PCOS. They were treated for 7-8 days with oral nitrendipine (10 mg, twice daily) or placebo using a double blind, cross-over design. Before and after treatment, blood samples were obtained for androgen and sex hormone-binding globulin determinations, and an oral glucose tolerance test was performed, measuring glucose and insulin. Both nitrendipine and placebo failed to decrease basal and stimulated insulin levels. Moreover, no significant variations in testosterone, dehydroepiandrosterone sulfate, or sex hormone-binding globulin concentrations were observed after either treatment. Therefore, these data fail to support previous suggestions that calcium channel blockers may play a role in the treatment of hyperandrogenism and hyperinsulinemia in obese women with PCOS.

Adult↗
PubMed1995

Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men.

There are no studies in vivo on the effects of insulin on androgens and sex hormone-binding globulin (SHBG) in men. We, therefore, investigated the effects of insulin suppression on testosterone and SHBG in two groups of eight nondiabetic adult obese men and six healthy normal weight men who underwent diazoxide treatment (100 mg, three times daily) for 7 days. Blood samples for hormone determination were obtained before the subjects had been selected for the study, immediately before diazoxide administration, and on the last day of treatment. A 24-h oral glucose tolerance test was also performed for glucose, insulin, and C-peptide determinations before and on the last day of treatment. Only one subject experienced significant side-effects, and no significant changes in mean body weight were found during the treatment. Diazoxide administration worsened glucose tolerance in several subjects and reduced fasting and glucose-stimulated insulin levels by approximately 50% in both control and obese subjects. No significant difference was present between historical and pretreatment hormone values in either group. Moreover, there were no differences in pretreatment gonadotropin and SHBG concentrations between the two groups, whereas testosterone (free and total) levels were lower in the obese than in the control subjects. After diazoxide administration, testosterone (free and total) decreased slightly, but significantly, whereas LH and SHBG significantly increased in both groups. Diazoxide treatment increased estradiol levels in controls, but not in obese men. In conclusion, these results indicate that in vivo, insulin is capable of stimulating testosterone production and, simultaneously, of inhibiting SHBG concentrations in both normal weight and obese men.

Adult↗