Management of gallstones and its related complications.

The majority of gallstone patients remain asymptomatic; however, interest toward the gallstone disease is continuing because of the high worldwide prevalence and management costs and the development of gallstone symptoms and complications. For cholesterol gallstone disease, moreover, a strong link exists between this disease and highly prevalent metabolic disorders such as obesity, dyslipidemia, type 2 diabetes, hyperinsulinemia, hypertriglyceridemia and the metabolic syndrome. Information on the natural history as well as the diagnostic, surgical (mainly laparoscopic cholecystectomy) and medical tools available to facilitate adequate management of cholelithiasis and its complications are, therefore, crucial to prevent the negative outcomes of gallstone disease. Moreover, some risk factors for gallstone disease are modifiable and some preventive strategies have become necessary to reduce the onset and the severity of complications.

Association between follicular fluid leptin and serum insulin levels in nonoverweight women with polycystic ovary syndrome.

AIMS: We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in vitro fertilization/embryo transfer (IVF). MATERIALS AND METHODOLOGY: We recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women (control-NOW). All women underwent IVF. Androgens, 17- ß -estradiol (17 ß -E2), and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin). RESULTS: In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. CONCLUSIONS: Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance.

Links between metabolic syndrome and cardiovascular autonomic dysfunction.

BACKGROUND: Type 2 diabetes (T2D) might occur within metabolic syndrome (MbS). One of the complications of T2D is an impaired (imp) cardiovascular autonomic function (CAF). AIMS: In subjects with T2D and age ≤ 55 years, the prevalence of impCAF and its relationship with BMI, waist, HbA(1c) values, MbS, hypertension, and family history of T2D and/or hypertension were analysed. METHODS: 180 subjects consecutively undergoing a day hospital for T2D were studied. The IDF criteria were used to diagnose MbS. To detect impCAF, 5 tests for the evaluation of CAF were performed with Cardionomic (Meteda, Italy). Univariate and multivariate analyses were performed. RESULTS: The prevalence of impCAF and MbS were 33.9% and 67.8%, respectively. Among diabetics with impCAF, 86.9% had MbS. ImpCAF was significantly associated with MbS, overweight, and HbA(1c) > 7%. Both logistic (P = 0.0009) and Poisson (P = 0.0113) models showed a positive association between impCAF and MbS. The degree of ImpCAF showed a positive linear correlation with BMI and HbA(1c) values. CONCLUSIONS: The study demonstrates that glycaemic control and overweight influence CAF and that T2D + MbS is more strongly associated with impCAF than isolated T2D. We suggest that MbS not only increases the cardiovascular risk of relatively young subjects with T2D but is also associated with impCAF.

The effects of weight loss due to gastric banding and lifestyle modification on red blood cell aggregation and deformability in severe obese subjects.

OBJECTIVE: To investigate the changes in the aggregation index (AI) and the elongation index (EI), in severe obese subjects (MbObS) undergoing laparoscopic adjustable gastric banding (LAGB). AI and EI are measured by Laser assisted Optical Rotational Red Cell Analyzer (LORCA) and are markers of erythrocyte aggregation and deformability, respectively. DESIGN AND SUBJECTS: Before, 3 and 6 months after LAGB plus lifestyle changes (Mediterranean diet plus daily moderate exercise), we evaluated AI, EI, body mass index (BMI), total (ToT) cholesterol (Chol), high-density lipoprotein (HDL)-Chol, low-density lipoprotein (LDL)-Chol, triglycerides and fasting glucose and insulin levels in 20 MbObS. The Student's t-test was used for comparisons between independent groups and the analysis of variance to assess differences in AI and EI at the 3 time points. Pearson's correlation coefficient was used to assess correlation among continuous variables and multiple linear regression analysis to assess predictive factors for AI and EI changes. RESULTS: BMI and all blood parameters showed a statistically significant decline 3 and 6 months after LAGB as compared with basal, except for EI and HDL-Chol that significantly increased. Stepwise selection of predictors shows that at 3 and 6 months, EI values depended on HDL-Chol values at the same time point. In the EI model, blood glucose was also statistically significant at 6 months. CONCLUSION: Our data show a significant improvement in EI after LAGB-induced weight loss, which correlates with an improved lipid pattern and support the idea that the rapid weight loss induced by LAGB plus lifestyle changes might reduce the thromboembolic risk and the high mortality risk found in MbObS.

Fat depot-related differences in gene expression, adiponectin secretion, and insulin action and signalling in human adipocytes differentiated in vitro from precursor stromal cells.

AIM/HYPOTHESIS: The distinct metabolic properties of visceral and subcutaneous adipocytes may be due to inherent characteristics of the cells that are resident in each fat depot. To test this hypothesis, human adipocytes were differentiated in vitro from precursor stromal cells obtained from visceral and subcutaneous fat depots and analysed for genetic, biochemical and metabolic endpoints. METHODS: Stromal cells were isolated from adipose tissue depots of nondiabetic individuals. mRNA levels of adipocyte-specific proteins were determined by real-time RT-PCR. Insulin signalling was evaluated by immunoblotting with specific antibodies. Glucose transport was measured by a 2-deoxy-glucose uptake assay. Adiponectin secretion in the adipocyte-conditioned medium was determined by a specific RIA. RESULTS: With cell differentiation, mRNA levels of PPARG, C/EBPalpha (also known as CEBPA), AP2 (also known as GTF3A), GLUT4 (also known as SLC2A4) were markedly upregulated, whereas GLUT1 (also known as SLC2A1) mRNA did not change. However, expression of C/EBPalpha, AP2 and adiponectin was higher in subcutaneous than in visceral adipocytes. By contrast, adiponectin was secreted at threefold higher rates by visceral than by subcutaneous adipocytes while visceral adipocytes also showed two- to threefold higher insulin-stimulated glucose uptake. Insulin-induced phosphorylation of the insulin receptor, IRS proteins, Akt and extracellular signal-regulated kinase-1/2 was more rapid and tended to decrease at earlier time-points in visceral than in subcutaneous adipocytes. CONCLUSIONS/INTERPRETATION: Subcutaneous and visceral adipocytes, also when differentiated in vitro from precursor stromal cells, retain differences in gene expression, adiponectin secretion, and insulin action and signalling. Thus, the precursor cells that reside in the visceral and subcutaneous fat depots may already possess inherent and specific metabolic characteristics that will be expressed upon completion of the differentiation programme.

Glucose transporter (GLUT-4) is targeted to secretory granules in rat atrial cardiomyocytes.

The insulin-responsive glucose transporter GLUT-4 is found in muscle and fat cells in the trans-Golgi reticulum (TGR) and in an intracellular tubulovesicular compartment, from where it undergoes insulin-dependent movement to the cell surface. To examine the relationship between these GLUT-4-containing compartments and the regulated secretory pathway we have localized GLUT-4 in atrial cardiomyocytes. This cell type secretes an antihypertensive hormone, referred to as the atrial natriuretic factor (ANF), in response to elevated blood pressure. We show that GLUT-4 is targeted in the atrial cell to the TGR and a tubulo-vesicular compartment, which is morphologically and functionally indistinguishable from the intracellular GLUT-4 compartment found in other types of myocytes and in fat cells, and in addition to the ANF secretory granules. Forming ANF granules are present throughout all Golgi cisternae but only become GLUT4 positive in the TGR. The inability of cyclohexamide treatment to effect the TGR localization of GLUT-4 indicates that GLUT-4 enters the ANF secretory granules at the TGR via the recycling pathway and not via the biosynthetic pathway. These data suggest that a large proportion of GLUT-4 must recycle via the TGR in insulin-sensitive cells. It will be important to determine if this is the pathway by which the insulin-regulatable tubulo-vesicular compartment is formed.

34-day total fast in an adult man.

The aim of this work was to investigate the changes of cardiac performance by both electrocardiography (ECG) and echocardiography (ECHOc), in addition to anthropometric and hormonal variables before, during and after prolonged total fasting (TF) and re-feeding in an overweight adult man. Physical examination, laboratory and hormonal measurements, ultrasonographic study of body fat distribution, ECG and ECHOc study were performed before during and after 34 days of TF and after 17 days of isocaloric re-feeding. The subject was a 52-year old Caucasian who was overweight with increased abdominal fat content (BMI: 28.6; W/H ratio: 0.95) and increased levels of arterial systolic and diastolic blood pressure (SBP, DBP). HPLC measurements of urinary catecholamine levels (HPLC), ECHOc study of cardiac performance, ultrasonographic study of body fat distribution were performed. The subject starved for 34 days losing 22kg, but after that time he was compelled to re-feed because of nausea and severe vomiting. A marked ketosis (ketonuria > 1200mg/day) was already present after 6 days of TF. After 17 days of TF norepinephrine (NE) and epinephrine (EPI) urinary levels showed a two-fold and nine-fold increase respectively, but they became undetectable at the end of TF. After 17 days of re-feeding catecholamine urinary levels were similar to those measured after 17 days of TF. After both TF and 17-day isocaloric re-feeding we found a decrease of visceral fat content and W/H ratio reached the normal values for age-matched subjects (W/H ratio after TF: 0.80, after re-feeding: 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)

The free testosterone to dehydroepiandrosterone sulphate molar ratio as a marker of visceral fat accumulation in premenopausal obese women.

The aim of this paper was to investigate the relationship between sex hormones and fat distribution in premenopausal obese women. Serum concentrations of sex hormones, glucose tolerance and fat distribution were determined in a population of non-diabetic obese women, in the outpatient clinic of University Hospital, Bari, Italy. The subjects were 40 consecutive premenopausal obese women (BMI > 25). The amounts of visceral, abdominal subcutaneous, and femoral subcutaneous fat, and the visceral to abdominal subcutaneous fat ratio were measured by ultrasound techniques. Serum concentrations of total testosterone (T), free testosterone (FT), dehydroepiandrosterone sulphate (DHEAS), delta 4-androstenedione (A), 17-beta-estradiol (E2), sex hormone binding globulin (SHBG), and the FT to DHEAS molar ratio were measured during the follicular phase. Plasma glucose and insulin concentrations were evaluated during an oral glucose tolerance test. Of all sex hormones, the FT/DHEAS molar ratio was the parameter that most closely related to the amount of visceral fat (r: 0.544, P < 0.001), and this positive association was maintained (P < 0.01) after adjustment for age, BMI and insulin levels (fitted model: R2 adjusted: 0.504; F ratio: 14.73; P-value: < 0.0001). DHEAS was inversely correlated with the amount of visceral fat (r: -0.324, P < 0.05). T was inversely correlated with the amounts of both abdominal subcutaneous (r: -0.409, P < 0.01) and visceral fat (r: -0.324, P < 0.05). The FT to DHEAS molar ratio is the androgenic parameter that most closely relates to the accumulation of visceral fat in premenopausal obese women.

Reduced effectiveness of atrial natriuretic factor in pre-menopausal obese women.

It is well-known that the prevalence of hypertension progressively increases with body weight. Since the major physiological activities of atrial natriuretic factor (ANF) are its natriuretic, diuretic and vasodilatory effects, the aim of the present study was to investigate the ANF basal plasma levels and platelet receptor number in 15 young normotensive obese (O) and 12 age-matched normal weight healthy (C) women. ANF effectiveness was also studied in eight of the obese and seven of the control women, after an intravenous bolus of the hormone (human ANF (99-126): 0.5 mg/kg body weight). Results are expressed as means+s.d. Basal ANF plasma levels were similar between obese (18.2 +/- 9.7 pg/ml) and control women (12.3 +/- 7.7 pg/ml), whereas obese patients showed an increase density of platelet ANF-binding sites (clearance receptors) (C: 28.7 +/- 33.5 fmol/10(9) cells; O: 39.6 +/- 4.6 fmol/10(9) cells; P < 0.001), without apparent differences in receptor affinity (Kd) (C: 6.0 +/- 3.0 pM; O: 7.0 +/- 2.0 pM). The biological response to ANF, evaluated by changes of mean blood pressure levels (C: 5 +/- 1 mmHg; O: 1 +/- 1 mmHg; P < 0.001) and the percentage increase of diuresis (C: 159 +/- 52%; O: 81 +/- 62%; P < 0.01) and natriuresis (C: 205 +/- 129%; O: 99 +/- 41%; P < 0.05) was significantly reduced in obese patients. The percentage increase in sodium excretion was inversely related to the basal insulin concentrations in the obese group (r = 0.64, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate in obese women.

Severe obesity is known to reduce either dehydroepiandrosterone circulating levels or growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. The present study was undertaken to evaluate the possibility of a relationship between the circulating levels of IGF-1 and those of dehydroepiandrosterone sulphate (DHEAS) in 25 fertile obese women. A logarithmic transformation of the values of non-normally distributed variables was performed before statistical analysis. We found a significant positive correlation between DHEAS and IGF-1 (r = 0.615, P < 0.01). In addition, stepwise multiple regression analysis showed that IGF-1 maintained a strong positive relationship with DHEAS (P < 0.01) when adjusted for other variables such as age, body mass index (BMI), waist:hip ratio (WHR) and insulin levels (adjusted R2 = 0.373; P < 0.01). These findings suggest that IGF-1 may independently influence the DHEAS circulating levels. ADG (5 alpha-androstan-3 alpha, 17 beta-diol-glucuronide) was also positively correlated to IGF-1 (r = 0.436, P < 0.05). However, when ADG concentrations were adjusted for DHEAS levels, this metabolite was not significantly correlated with IGF-1, thus excluding a direct influence of IGF-1 on the 5-alpha-reductase activity. Therefore, although our data represent only a preliminary study, they seem to suggest a possible influence of IGF-1 on circulating levels of DHEAS in obese women.

Analysis of uncoupling protein and its mRNA in adipose tissue deposits of adult humans.

Brown adipose tissue (BAT) is a specialized adipose tissue whose specific marker is the uncoupling protein (UCP). UCP and its mRNA were previously detected in the perirenal fat of several adult subjects undergoing surgery for pheochromocytoma. We have investigated the possible association of the presence of UCP and its mRNA with pathological conditions other than pheochromocytoma. We obtained adipose tissue from both the periadrenal and the perirenal regions of 36 subjects: group A: human infants (n = 6); group B: adult subjects (n = 11) undergoing surgery for pheochromocytoma; group C: adult subjects (n = 9) undergoing surgery for other endocrine pathologies; group D: adult patients (n = 10) operated for non-endocrine pathologies. In all subjects of group A UCP was detectable by Western analysis. Interestingly, in two newborns, we also found a positive signal for UCP in the peristernal and the retroperitoneal adipose tissues as well as in the perirenal fat. We also identified UCP in eight cases in group B, in five cases in group C and six cases in group D. The human H-UCP-0.5 genomic probe detected a typical BAT mRNA in the periadrenal adipose tissue of all subjects of groups B, C and D showing a positive Western blot. Our results confirm the presence of well-developed BAT in human infants, as well as in adults with pheochromocytoma. They also suggest that human BAT UCP and UCP mRNA are present in adult subjects in pathological conditions other than pheochromocytoma. It might be argued that certain hormones distinct from catecholamine could activate BAT development in human adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of free testosterone on antigen levels of plasminogen activator inhibitor-1 in premenopausal women with central obesity.

Women with upper body obesity are at increased risk for cardiovascular disease (CVD). Several studies have demonstrated a reduced fibrinolytic activity in these patients, mainly due to an enhanced activity of plasminogen activator inhibitor-1 (PAI-1). Since an increase of androgenic activity is a feature of central obesity in women, the present study was aimed at evaluating the possibility of a relationship between androgens and PAI-1 (antigen and activity) in 20 premenopausal women, 10 with upper body obesity and 10 controls. In obese women, PAI-1 antigen showed a positive Pearson correlation with free testosterone (FT), insulin, c-peptide, triglycerides (TG), and waist to hip ratio (WHR) (P less than .01), whereas PAI-1 activity correlated positively only with insulin and WHR (P less than .01). In control women, PAI-1 antigen and activity were positively related only to TG (P less than .01). When we applied the multiple regression model with stepwise backward method to our data, both PAI-1 antigen and activity did not maintain any significant association. However, when the data from both the groups were pooled (n = 20), and PAI-1 antigen was considered as the dependent variable, body weight (Sig T = 0.0001), TG (Sig T = 0.0053), FT (Sig T = 0.013), and luteinizing hormone (LH) (Sig T = 0.0474) met the stepwise criteria, suggesting an independent effect of each of these parameters on PAI-1 antigen. On the other hand, when PAI-1 activity was tested as the dependent variable, only body weight maintained a significant relationship with this parameter (Sig T = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

Inverse relationship between cortisol excretion rate and plasminogen activator inhibitor-1 (PAI-1) antigen and activity in premenopausal obese women.

The present study was undertaken in order to investigate the possibility of a relationship between plasminogen activator inhibitor-1 (PAI-1) and cortisol excretion rate in 15 obese women. We found a highly significant linear inverse correlation between cortisol excretion rate and both PAI-1 antigen (r = 0.79, P less than 0.001) and activity (r = 0.77, P less than 0.001). In addition, stepwise regression analysis showed that cortisol excretion rate maintained a strong negative relationship with PAI-1 antigen (significance level 0.03) and activity (significance level 0.003), when adjusted for other variables taken in examination (waist to hip ratio, body mass index, insulin, DHEAS, age). Even though this study only demonstrates a negative correlation, the possibility of a direct inhibitory effect of cortisol on PAI-1 production should be considered. In conclusion, the present study demonstrates an inverse correlation between cortisol excretion rate and PAI-1 antigen and activity, suggesting a possible role for cortisol in protecting obese women from reduced fibrinolytic activity.

Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index.

Dehydroepiandrosterone (DHEA) has an anti-obesity effect in rodents and reduces body fat in normal men. Therefore, the plasma levels of DHEA were evaluated in nine premenopausal healthy women and in 13 menstrually active nondiabetic obese women, including patients (n = 6) with body mass index (BMI) over 40. In the obese group, a significant inverse correlation between DHEA levels and BMI was found. These results suggest that patients with severe obesity are unable to increase the DHEA adrenal production rate in order to parallel the increase in the hormone metabolic clearance rate (due to enlargement of body fat mass per se). The deficiency of this mechanism might itself contribute to the progressive fat accumulation in severe obesity.

Changes in overall plasma norepinephrine turnover and lymphomonocyte beta-adrenoceptor number during combined caloric and sodium restriction in normotensive obese subjects.

The aim of the study was to evaluate in eight normotensive obese patients the influence of low sodium intake (9 mEq/day) on the sympathetic activity modifications induced by caloric restriction (2511 kJ/day). As compared to the isocaloric salt balanced diet, 7 days of normosodic underfeeding induced a decrease in the overall norepinephrine turnover (clearance and appearance rate) and 24 hours urinary output, whereas the combined caloric and salt restriction significantly increased the norepinephrine appearance rate and even more the norepinephrine clearance but, on the other hand, decreased the beta-adrenergic receptor number on the lymphomonocyte surface, suggesting a reduced peripheral sensitivity to catecholamines. Therefore, the utility of the combined sodium and caloric restriction in the treatment of the normotensive obese patients remains still questionable.

[Adenylate cyclase response to beta-adrenergic agonists in heart and brown adipose tissue]. / Risposta dell'adenilciclasi ad agonisti beta-adrenergici in cuore e tessuto adiposo bruno.

Some sympathomimetic compounds (i.e. BRL37344) increase brown adipose tissue (BAT) thermogenesis with minimal cardiac effects. They act through an "atypical" beta-adrenergic receptor (beta-AR). Since beta-AR responses involve Adenylate Cyclase (AC) activation, we investigate the AC answer to isoproterenol and BRL37344 in rat plasmamembranes of heart (beta 1-ARs) and BAT (atypical beta-ARs). AC dose-response curves were obtained by incubating membrane fractions with different concentrations of isoproterenol and BRL37344 (1 nM-100 microM) at 25 degrees C for 15 min. In our study BRL37344 is 40-times more potent than isoproterenol in stimulating AC activity of BAT (EC50s: BRL37344 = 0.02 microM, isoproterenol = 0.7 microM). Furthermore it is more potent in stimulating BAT AC than heart AC (BRL37344 EC50 ratio heart/BAT = 38). However on BAT membranes, BRL37344 intrinsic sympathomimetic activity (ISA) vs. Isoproterenol is 0.87. Since isoproterenol and BRL37344 show a similar ISA for BAT respiration and lipolysis, we may argue that AC maximal activity is not required for maximal lipolytic and thermogenic responses.

D-(-)-beta-hydroxybutyrate inhibits catecholamine-stimulated lipolysis and decreases beta-adrenoceptors' affinity in human fat cells but not in lymphomonocytes.

The effect of D-(-)-beta-hydroxybutyrate, at concentrations commonly achieved during ketoacidosis in humans (10 mmol/l), on human fat cell lipolysis in vitro was the aim of this study. The basal lipolysis was not modified and beta-hydroxybutyrate did not affect forskolin- or dibutyryl-cAMP-stimulated glycerol release, whereas it markedly inhibited isoproterenol-stimulated lipolysis. In membranes of intact adipocytes exposed to D-(-)-beta-hydroxybutyrate for 1 h, we found a decrease in beta-adrenoceptor affinity in saturation experiments and a shift to the right of the isoproterenol-mediated radioligand [( 125I]-cyanopindolol) displacement curve. These findings suggest that beta-hydroxybutyrate inhibits catecholamine-stimulated lipolysis by decreasing beta-adrenoceptor affinity. No effect of beta-hydroxybutyrate was found on beta-adrenoceptor binding of intact mononuclear cells of peripheral blood. In conclusion, the beta-adrenoceptor affinity lowering effect of beta-hydroxybutyrate is seemingly specific to human fat cells and might represent a feed-back mechanism that prevents an uncontrolled breakdown of triglycerides and indirectly regulates its own production rate.

Influence of lactate on isoproterenol-induced lipolysis and beta-adrenoceptors distribution in human fat cells.

The influence of lactate on human adipocytes lipolysis and the possible relationship between lactate-induced metabolic effects and beta-adrenoceptor binding sites were investigated. beta-sites were identified in membranes with (125I)-cyanopindolol and in intact cells with (125I)-cyanopindolol and (3H)-CGP 12177. Lactate reduced isoproterenol-induced lipolysis in a dose-response fashion and such inhibition became significant only at 16 mmol/l lactate. Exposure of human fat cells to 16 mmol/l lactate significantly reduced beta-adrenoceptors density on crude membranes. When the binding assay was performed on intact cells using (125I)-cyanopindolol at 37 degrees C, the radioligand identified the same number of receptors, regardless of the presence of lactate in the preincubation medium. When (3H)-CGP 12177 was used, it bound to about 35% less receptors in lactate pre-treated cells than in control. Seemingly, at 37 degrees C, because of its lipophilicity, (125I)-cyanopindolol can cross the plasma membrane and bind to intracellular sites whereas, (3H)-CGP 1277, due to its hydrophilicity, identifies surface receptors only. Thus, the present in vitro study provides evidence that high levels of lactate, similar to the concentrations usually achieved in overt lactic acidosis, are able per se to inhibit human lipolysis and to redistribute beta-adrenoceptors from cell surface to a domain not accessible to hydrophilic ligands.

Biophysical and endocrine-metabolic changes during menopausal hot flashes: increase in plasma free fatty acid and norepinephrine levels.

Thermocutaneous, vascular, metabolic and hormonal changes were investigated during 11 hot flashes from 6 postmenopausal women. The first detectable change was an increase in finger blood flow with a concomitant enhancement of skin conductance. The increase in skin conductance was followed rapidly by a sharp rise in finger temperature. The main endocrine-metabolic changes associated with the above phenomena were a sharp increase in plasma free fatty acids (approximately 65%), norepinephrine (approximately 100%) and LH (approximately 20%) levels. Plasma glucose and cortisol tended to be increased but did not reach statistical significance; on the other hand, plasma insulin, glucagon, growth hormone, epinephrine and dopamine remained unchanged.