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-Heaith 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.
OBJECTIVE
There is emerging evidence that women with visceral obesity may have hyper‐responsiveness of the hypothalamic–pituitary–adrenal axis. There are no studies on basal daily secretory pattern ...of ACTH and cortisol in subjects with different obesity phenotypes.
DESIGN AND PATIENTS
In this study we examined daytime pulsatile secretion of ACTH and cortisol in two groups of premenopausal obese women with visceral (V‐BFD) (BMI 37.1 ± 1.7) and subcutaneous (S‐BFD) (BMI 38.8 ± 1.5) body fat distribution (measured by CT scan) and in a group of normal weight healthy controls (BMI 21.1 ± 0.5). After an overnight fast, blood samples were taken at 15‐minute intervals for 12 h (49 samples, from 0800 h until 2000 h). All women avoided breakfast but had a normal lunch and dinner, both containing similar food, energy and nutrient composition. ACTH and cortisol responses to mixed meals at noon and in the evening were also investigated.
RESULTS
Mean values of ACTH and cortisol did not differ between the groups. However, ACTH pulse frequency was significantly higher in V‐BFD (P < 0.06) and S‐BFD (P < 0.02) obese women than in controls, without any significant differences between the two obese subgroups. Mean ACTH pulse amplitude was lower in the V‐BFD than in S‐BFD obese (P < 0.02) and control (P < 0.05) groups. Cortisol episodic characteristics did not differ between V‐BFD and S‐BFD obese and controls. All differences in ACTH pulsatile parameters between obese and controls and between the two obese subgroups were evident only in the morning, with no further significant differences during the early and late afternoon. There were no significant differences in cortisol parameters during the three periods of the day between the various groups, apart from late afternoon cortisol pulse frequencies, which were significantly lower in V‐BFD than in controls. After lunch, ACTH and cortisol levels significantly increased in all groups, but the cortisol increase tended to be more rapid in V‐BFD than in the other two groups. After dinner, ACTH significantly increased in V‐BFD and controls but not in the S‐BFD group, whereas cortisol rose significantly in all groups, but significantly less in S‐BFD than in V‐BFD and controls. CortisolAUC (but not ACTHAUC) after lunch was significantly higher than after dinner in all groups. ACTH response after each meal was similar in all groups, but cortisolAUC after dinner was significantly lower in S‐BFD than in V‐BFD women.
CONCLUSION
This study demonstrates that in premenopausal women, obesity, particularly the visceral phenotype, is associated with several abnormalities of ACTH pulsatile secretion, particularly in the morning. On the contrary, no major differences were present in either blood concentrations, diurnal rhythm or secretory pattern of cortisol between obese and controls. The responses to meals seem to indicate a much more rapid cortisol response after lunch in women with visceral obesity and a reduced activation of the hypothalamic–pituitary–adrenal axis after dinner in women with subcutaneous obesity.
Low energy lasers are widely used to treat a variety of musculoskeletal conditions including fibromyalgia, despite the lack of scientific evidence to support its efficacy. A randomised, single-blind, ...placebo-controlled study was conducted to evaluate the efficacy of low-energy laser therapy in 40 female patients with fibromyalgia. Patients with fibromyalgia were randomly allocated to active (Ga-As) laser or placebo laser treatment daily for two weeks except weekends. Both the laser and placebo laser groups were evaluated for the improvement in pain, number of tender points, skinfold tenderness, stiffness, sleep disturbance, fatigue, and muscular spasm. In both groups, significant improvements were achieved in all parameters (p<0.05) except sleep disturbance, fatigue and skinfold tenderness in the placebo laser group (p>0.05). It was found that there was no significant difference between the two groups with respect to all parameters before therapy whereas a significant difference was observed in parameters as pain, muscle spasm, morning stiffness and tender point numbers in favour of laser group after therapy (p<0.05). None of the participants reported any side effects. Our study suggests that laser therapy is effective on pain, muscle spasm, morning stiffness, and total tender point number in fibromyalgia and suggests that this therapy method is a safe and effective way of treatment in the cases with fibromyalgia.
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 (n = 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.
Adrenal and gonadal function in obesity PASQUALI, R; VICENNATI, V; GAMBINERI, A
Journal of endocrinological investigation,
2002, Letnik:
25, Številka:
10
Journal Article
Summary
BACKGROUND Abdominal obesity is associated with hyper‐responsiveness of the hypothalamic‐pituitary‐adrenocortical (HPA) axis to stimulatory neuropeptides and to stress. Catecholamines are ...involved in the regulation of the HPA axis, particularly during stress, via α‐adrenoceptor modulation.
DESIGN In this study, we investigated the effects of pre‐treatment with an α2‐adrenoceptor agonist, clonidine (2μg/kg over 10 minutes) and antagonist, yohimbine (0.125 mg/kg bolus, followed by 0.001 mg/ kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol response to combined CRH (human, 100μg) plus AVP (0.3 IU) administration, and on noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese women with abdominal (A‐BFD) or peripheral (P‐BFD) body fat distribution and in nonobese controls.
RESULTS During the control CRH+AVP test the ACTH but not the cortisol response was higher (P<0.05) in obese A‐BFD women than In controls, with minor and transient variations of NA levels. Neither the control test nor clonidine or yohimbine influenced basal or post CRH + AVP A concentrations. Clonidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH response to CRH + AVP. Conversely, during yohimbine infusion NA levels steadlly and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A‐BFD group significantly (P<0.05) more than in the P‐BFD group.
CONCLUSIONS This study shows that α2‐adrenoceptor regulation of the HPA axis is different in obese and nonobese women, particularly in stressed conditions. We suggest that the abnormal ACTH response to CRH+AVP challenge with increased noradrenergic tone may represent a specific pathophysiological aspect of the abnormal response to stress or to other specific stimulatory factors in obese women, particularly those with abdominal body fat distribution.
The ability of Cannabis sativa (marijuana) to increase hunger has been noticed for centuries, although intensive research on its molecular mode of action started only after the characterization of ...its main psychoactive component Delta super(9)-tetrahydrocannabinol in the late 1960s. Despite the public concern related to the abuse of marijuana and its derivatives, scientific studies have pointed to the therapeutic potentials of cannabinoid compounds and have highlighted their ability to stimulate appetite, especially for sweet and palatable food. Later, the discovery of specific receptors and their endogenous ligands (endocannabinoids) suggested the existence of an endogenous cannabinoid system, providing a physiological basis for biological effects induced by marijuana and other cannabinoids. Epidemiological reports describing the appetite-stimulating properties of cannabinoids and the recent insights into the molecular mechanisms underlying cannabinoid action have proposed a central role of the cannabinoid system in obesity. The aim of this review is to provide an extensive overview on the role of this neuromodulatory system in feeding behavior by summarizing the most relevant data obtained from human and animal studies and by elucidating the interactions of the cannabinoid system with the most important neuronal networks and metabolic pathways involved in the control of food intake. Finally, a critical evaluation of future potential therapeutical applications of cannabinoid antagonists in the therapy of obesity and eating disorders will be discussed.
Abdominal obesity is associated with hyper-responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to stimulatory neuropeptides and to stress. Catecholamines are involved in the ...regulation of the HPA axis, particularly during stress, via alpha-adrenoceptor modulation.
In this study, we investigated the effects of pre-treatment with an alpha2-adrenoceptor agonist, clonidine (2 microg/kg over 10 minutes) and antagonist, yohimbine (0.125 mg/kg bolus, followed by 0. 001 mg/kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol response to combined CRH (human, 100 microg) plus AVP (0.3 IU) administration, and on noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese women with abdominal (A-BFD) or peripheral (P-BFD) body fat distribution and in nonobese controls.
During the control CRH + AVP test the ACTH but not the cortisol response was higher (P < 0.05) in obese A-BFD women than in controls, with minor and transient variations of NA levels. Neither the control test nor clonidine or yohimbine influenced basal or post CRH + AVP A concentrations. Clonidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH response to CRH + AVP. Conversely, during yohimbine infusion NA levels steadily and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A-BFD group significantly (P < 0.05) more than in the P-BFD group.
This study shows that alpha2-adrenoceptor regulation of the HPA axis is different in obese and nonobese women, particularly in stressed conditions. We suggest that the abnormal ACTH response to CRH + AVP challenge with increased noradrenergic tone may represent a specific pathophysiological aspect of the abnormal response to stress or to other specific stimulatory factors in obese women, particularly those with abdominal body fat distribution.
