PubMed Health⌕ Search

Biomedical subjects

A Gambineri

Publications and source records attributed to A Gambineri.

At least 19 recordsLinked to original sources
PubMed2006

The impact of obesity on reproduction in women with polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.

Adipose Tissue↗
PubMed2005

Short-term modification of sex hormones is associated with changes in ghrelin circulating levels in healthy normal-weight men.

The aim of this study was to evaluate the effect of selective and short-term sex hormone modifications on ghrelin levels in normal-weight eugonadal men undergoing hormonal contraceptive treatments. Seven men received an oral progestin [cyproterone acetate (CPA) or dienogest (DNG)] 10 mg/day for 3 weeks (CPA-DNG group), 7 CPA orally 5 mg/day in association with testosterone enanthate (TE) im 200 mg/week for 8 weeks (CPA-TE group), and 7 placebo (PLAC) for 8 weeks (PLAC group). Anthropometry and blood levels of LH, FSH, testosterone, estradiol, glucose, insulin and total ghrelin were evaluated. At baseline, no parameters differed among the three groups. After treatment, LH and FSH decreased in both CPA-DNG and CPA-TE groups, whereas they did not change in the PLAC group. Testosterone and estradiol decreased in the CPA-DNG group to the hypogonadal range, increased in the CPA-TE group to supraphysiological concentrations and, as expected, remained unchanged in the PLAC group. Total ghrelin levels increased in the CPA-DNG, decreased in the CPA-TE and did not change in the PLAC group. Ns modifications in the other parameters were observed in any group, demonstrating that the short-term changes of circulating sex hormones are able to modify ghrelin levels. These data, therefore, suggest that sex steroids are important regulators of ghrelin in normal-weight healthy men too.

Adult↗
PubMed2005

Metabolic alterations and cardiovascular risk factors in the polycystic ovary syndrome.

Available literature indicates that polycystic ovary syndrome (PCOS) represents a condition with a high prevalence of the metabolic syndrome, a greater and precocious appearance of glucose intolerance states, including type 2 diabetes mellitus, and a potentially greater risk for cardiovascular diseases. With respect to metabolic disorders, however, there is also emerging evidence that they are more prevalent in PCOS rather than in the general population, and that there are regional differences in the world, depending on lifestyle and other environmental factors. This evidence should be taken into consideration in future strategies focusing on prevention of metabolic and cardiovascular disorders in PCOS, not only on treatment of infertility and signs of androgen excess.

Cardiovascular Diseases↗
PubMed2004

Response of the hypothalamic-pituitary-adrenal axis to small dose arginine-vasopressin and daily urinary free cortisol before and after alprazolam pre-treatment differs in obesity.

OBJECTIVE: Arginine vasopressin (AVP) has a central role in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress conditions. A low dose of AVP has been shown to have a modest, but significant effect on ACTH response in normal weight subjects. The aim of this study was to test the response of the HPA axis in obese subjects in order to assess eventual primary neuroendocrine alterations, previously demonstrated by using AVP combined with corticotropin releasing hormone (CRH). In addition, given its central inhibitory action on the HPA axis, we investigated whether the suppressive capacity of alprazolam (APZ) pretreatment on the hormone response to low-dose AVP challenge and daily urinary free cortisol (UFC) excretion rate may be altered in the presence of obesity. DESIGN: Fifteen overweight or obese women and eight normal-weight controls randomly underwent two low-dose AVP tests (0.3 UI iv bolus), one without (AVP test) and the other preceded by APZ administration (0.5 mg at midnight and 0.5 mg 90 min before the test in the morning at 08:30 h) (APZ/AVP test). Blood samples for ACTH and cortisol assay were obtained at baseline and throughout each test. The day before each test, 24h-UFC/ creatinine was also mea-sured. RESULTS: Basal ACTH levels were similar in the two groups, whereas cortisol concentrations were significantly lower in the overweight/obese group. Overweight/obese women had higher ACTH and cortisol responses to the AVP tests and significantly greater hormone inhibition after APZ than controls. In both groups, AVP-induced delta-peak cortisol values before and after APZ pre-treatment were significantly correlated. Body fat distribution had no effect on the HPA axis response to AVP either before or after APZ. Moreover, APZ decreased 24h-UFC/creatinine values unsignificantly in controls and by approximately 50% in the overweight/obese subjects. These changes were unrelated to the cortisol response to the AVP test before and after APZ pretreatment. On the other hand, percent changes of 24h-UFC/creatinine after APZ were negatively related to the body mass index (BMI) but positively with waist circumference values, which indicates that the abdominal obesity phenotype may counteract the 24 h-UFC/creatinine that would be expected on the basis of BMI values. CONCLUSIONS: Our data further support the concept that in women obesity may represent a condition of hyperresponsiveness or hypersensitivity of the HPA axis to neuroendocrine stimuli, which appear to be independent of feedback control. In addition, the data on the inhibiting capacity of APZ on UFC excretion confirm that the alterations of the HPA axis in obesity is particularly evident in the abdominal phenotype.

Adult↗
PubMed2004

Type 2 diabetes and the polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting women in reproductive age, characterized by chronic anovulation and hyperandrogenism. The etiology of PCOS is still unknown. However, several studies have suggested that insulin resistance plays an important role in the pathogenesis of the syndrome. As a consequence of insulin-resistance, women affected by PCOS often present abnormalities of glucose metabolism and lipid profile, and have an increased risk of type 2 diabetes and cardiovascular disease over-time. Besides insulin-resistance, it has been demonstrated that some of these women also have alterations in beta-cell-function. Both disorders (insulin-resistance and beta-cell-dysfunction) are recognized as major risk factors for the development of type 2 diabetes. Long-term studies, evaluating the glucose-insulin system in women affected by PCOS, have shown a higher incidence of glucose intolerance, including both impaired glucose tolerance and type 2 diabetes, compared to age and weight matched control populations. The risk of glucose intolerance among PCOS subjects seems to be approximately 5 to 10 fold higher than normal and appears not limited to a single ethnic group. Moreover, the onset of glucose intolerance in PCOS women has been reported to occur at an earlier age than in the normal population (approximately by the 3rd-4th decade of life). However, other risk factors such as obesity, a positive family history of type 2 diabetes and hyperandrogenism may contribute to increasing the diabetes risk in PCOS.

Adult↗
PubMed2003

Testosterone levels in obese male patients with obstructive sleep apnea syndrome: relation to oxygen desaturation, body weight, fat distribution and the metabolic parameters.

To investigate the impact of obstructive sleep apnea syndrome (OSAS) on testosterone levels and on the main parameters of the metabolic syndrome in abdominally obese men, 15 male subjects with abdominal obesity phenotype and polysomnographic diagnosis of OSAS (OB-OSAS) and 15 controls matched for age and anthropometric parameters (OB) were investigated. Anthropometry, SHBG, sex hormones and several parameters of the metabolic syndrome were measured. Only subjects with an Epworth Sleepiness Score greater than 10 underwent a polysomnographic study with calculation of the number of desaturation rates per sleeping hour (ODI), the minimal oxygen saturation during each desaturation episode (minSaO2) and the mean minimal arterial oxygen saturation for the whole night period (MminSaO2). Both total and free testosterone levels were lower in OB-OSAS than in OB patients. A negative correlation between polysomnographic parameters (ODI, minSaO2 and MminSaO2) and testosterone levels was found. The relationship between total and free testosterone and ODI persisted after adjusting for body mass index (BMI) and waist (W) values. Triglyceride and uric acid levels were significantly higher in OB-OSAS than in OB patients. A negative correlation between testosterone and acid uric level and a positive correlation between testosterone and HDL-cholesterol level was found, regardless of BMI and W circumference, particularly in the OB-OSAS group. Our study suggests that, in patients with obesity and OSAS, the severity of hypoxia during sleeping hours may be an additional factor in reducing testosterone levels, regardless of BMI and abdominal fatness. This may contribute in worsening metabolic abnormalities which, in men with OSAS, exceed those expected on the basis of degree of obesity and pattern of fat distribution.

Adipose Tissue↗
PubMed2003

Anti-androgen treatment increases circulating ghrelin levels in obese women with polycystic ovary syndrome.

In a previous study we were the first to describe a negative correlation between circulating ghrelin concentrations and androgen levels in human plasma, suggesting an interaction between ghrelin and the endocrine regulation of reproductive physiology. We now investigated a potential direct regulatory influence of circulating androgens on plasma ghrelin levels. Fourteen obese women with polycystic ovary syndrome (PCOS) on a hypocaloric diet were randomly assigned to treatment groups (open-labeled design), receiving either placebo (no.=7) or the antiandrogen flutamide (no.=7) for 6 months. Anthropometry, visceral (VAT) and subcutaneous (SAT) adipose tissue (quantified by computerized tomography), plasma hormone levels, insulin sensitivity indexes (Quantitative Insulin-Sensitivity Check Index-QUICKI) and Homeostatic Model Assessment applied to the oral glucose tolerance test (HOMA(OGTT)) were evaluated at baseline and at the end of the study. Body weight decreased and insulin resistance indexes improved in both groups. A tendency toward a greater loss of VAT was observed in the flutamide group. Only in the flutamide group was a significant reduction of androgens levels observed. Plasma ghrelin levels significantly increased following treatment with flutamide, while ghrelin remained unchanged in the placebo group. We observed a negative correlation between changes of ghrelin levels and changes of androgen plasma concentration in the flutamide-treated group. In the same group a positive correlation was found between plasma ghrelin changes and insulin sensitivity as expressed by HOMA(OGTT). Analysis in a multiple regression model, however, showed that plasma ghrelin changes were mainly due to changes of androgen levels rather than improved insulin sensitivity. We, therefore, conclude that androgens are independent modulators of circulating ghrelin concentrations.

Adult↗
PubMed2002

Adrenal and gonadal function in obesity.

Obesity is associated with multiple alterations of the endocrine systems, including abnormal circulating blood hormone concentrations, due to changes in their pattern of secretion and/or metabolism, altered hormone transport, and/or action at the level of target tissues. There is evidence that alterations of endocrine systems regulating sex hormones and corticosteroids may play a crucial role in the development of obesity, particularly the abdominal phenotype. Obese women are characterized by a condition of sc"functional hyperandrogenism", whereas in males, obesity is associated with reduced T levels and decreased LH secretory pattern from the pituitary. In addition, in both sexes a dysregulation of the hypothalamic-pituitary-adrenal axis has been reported, including both neuroendocrine and peripheral alterations, finally leading to inappropriately higher than normal exposure to F of peripheral tissues, particularly the visceral adipose tissue. By these mechanisms, it can be hypothesized that both visceral fat enlargement and alterations of insulin action and associated metabolic disturbances may develop, therefore predisposing abdominally obese individuals to Type 2 diabetes and cardiovascular disease.

Adipose Tissue↗
PubMed2002

Obesity and the polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is a condition characterized by hyperandrogenism and chronic oligo-anovulation. However, many features of the metabolic syndrome are inconsistently present in the majority of women with PCOS. Approximately 50% of PCOS women are overweight or obese and most of them have the abdominal phenotype. Obesity may play a pathogenetic role in the development of the syndrome in susceptible individuals. In fact, insulin possesses true gonadotrophic function and an increased insulin availability at the level of ovarian tissue may favour excess androgen synthesis. Obesity, particularly the abdominal phenotype, may be partly responsible for insulin resistance and associated hyperinsulinemia in women with PCOS. Therefore, obesity-related hyperinsulinemia may play a key role in favouring hyperandrogenism in these women. Other factors such as increased estrogen production rate, increased activity of the opioid system and of the hypothalamic-pituitary-adrenal axis, decreased sex hormone binding globulin synthesis and, possibly, high dietary lipid intake, may be additional mechanisms by which obesity favours the development of hyperandrogenism in PCOS. Irrespective of the pathogenetic mechanism involved, obese PCOS women have more severe hyperandrogenism and related clinical features (such as hirsutism, menstrual abnormalities and anovulation) than normal-weight PCOS women. This picture tends to be more pronounced in obese PCOS women with the abdominal phenotype. Body weight loss is associated with beneficial effects on hormones, metabolism and clinical features. A further clinical and endocrinological improvement can also be achieved by adding insulin-sensitizing agents and/or antiandrogens to weight reduction programmes. These obviously emphasize the role of obesity in the pathophysiology of PCOS.

Androgens↗
PubMed2001

Testosterone in ageing men.

A progressive decline in androgen levels is a common finding in men after middle age. The resulting clinical picture may be characterised by alterations in the physical and psychological domains, which have been demonstrated to correlate positively with testosterone serum levels. This clinical picture closely resembles the features of primary or secondary hypogonadism. Testosterone is the more convenient hormone for substitution therapy in classic hypogonadism as well as in age-related hypoandrogenism. Different choices of testosterone preparations are currently available, which are characterised by different routes of administration and by various pharmacokinetic profiles. Two major achievements urgently need to be investigated in the near future: the ability of the new formulations to reach more physiological and sustained hormone levels with the concomitant amelioration of their tolerability and the evidence of long-term prospective studies aimed at demonstrating the benefits and the possible complications of this therapy.

Aged↗
PubMed2000

Testosterone therapy in men: clinical and pharmacological perspectives.

There is increasing evidence that androgen therapy in men may be effectively applied in several conditions to improve well being and health. Classical indications for androgen therapy in males are represented by primary or secondary hypogonadism, delayed puberty, aplastic anemia and that secondary to chronic renal failure, protein wasting diseases such as trauma, burns, tumors and infectious diseases. Androgen innovating applications in men are represented by aging and visceral obesity associated with the metabolic syndrome. In addition, it is clear that appropriate testosterone treatment can be adequately used in male contraception, provided spermatogenesis is abolished and tolerability is adequate. Due to unphysiological hormone levels achieved by currently available testosterone preparations, new delivery systems have been produced to achieve more physiological and sustained hormone levels and improve tolerability and action at the levels of target tissues. Some of them are now available in several countries and new formulas are under development.

Aging↗
PubMed2000

alpha2-adrenoceptor regulation of the hypothalamic-pituitary-adrenocortical axis in obesity.

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 alpha-adrenoceptor modulation. DESIGN: 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. 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 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. CONCLUSIONS: 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.

Adrenergic alpha-Agonists↗
PubMed2000

Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo. Fasting insulin significantly decreased in both PCOS women and controls, regardless of treatment, whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin. Neither metformin or placebo significantly modified the levels of LH, FSH, dehydroepiandrosterone sulphate, and progesterone in any group, whereas testosterone concentrations decreased only in PCOS women treated with metformin. SHBG concentrations remained unchanged in all PCOS women; whereas in the control group, they significantly increased after both metformin and placebo. Leptin levels decreased only during metformin treatment in both PCOS and control groups. (ABSTRACT TRUNCATED)

Abdomen↗
PubMed1999

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome.

OBJECTIVES: To investigate the activity of the hypothalamic-pituitary-adrenal (HPA) axis in male obesity and its relationship with several prominent parameters of the metabolic syndrome. DESIGN: A cross-sectional clinical study of the activity of the HPA axis in groups of obese males and normal-weight controls. SUBJECTS: Seventeen obese non-diabetic males with a body mass index (BMI) >28 and eight normal-weight controls were examined. MEASUREMENTS: Fat free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance, and the waist-to-hip circumference ratio (WHR) was calculated in all subjects. Baseline samples were taken for sex hormone and lipid determination, and an oral glucose tolerance test (OGTT) was performed for glucose and insulin determination. The activity of the HPA axis was determined by the combined administration of human corticotropin releasing hormone (CRH) (100 microg) and arginine vasopressin (AVP) (0.3 IU). RESULTS: As expected, FFM and FM and the WHR were higher in obese men than in controls, as were fasting insulin and stimulated (as area under the curve (AUC)) glucose and insulin concentrations. Baseline adrenocorticotropin (ACTH) and cortisol concentrations were similar in both groups, but stimulated (as AUC), ACTH was higher (P < 0.05) in obese subjects than in controls, whereas no significant difference in cortisolAUC was present. Since the main differences between obese subjects and controls were present during the early 30 min of the test, the correlation coefficients between total and incremental ACTH(AUC 0-30 min) and CortisolAUC 0-30 min and all other variables were analyzed. A significant correlation coefficient was present between them and all anthropometric parameters, fasting insulin and insulinAUC, but not with androgens and gonadotrophins. In addition, a significant correlation was present between total and incremental ACTH(AUC 0-30 min) and triglyceride concentrations. However, after adjusting for BMI or FM values, all correlation coefficients became non-significant, except the one between incremental ACTH(AUC 0-30 min) and insulinAUC (P < 0.05). CONCLUSION: These findings indicate that obese men may also have an altered pituitary response to combined CRH/AVP stimulation, which appears to be predominantly related to body size and total body fat. ACTH hyperresponsiveness after CRH/AVP stimulation also appears to be related to hyperinsulinaemia, but underlying mechanisms of this relationship remain to be elucidated.

Adipose Tissue↗
PubMed1999

The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen-progestagen treatment.

OBJECTIVE: Little is known about the natural history of polycystic ovary syndrome (PCOS), although preliminary data indicate that affected women are more susceptible than the general population to diabetes and cardiovascular diseases at post-menopausal ages. The aim of this study was to follow-up all main features of the metabolic syndrome in a group of young women with PCOS and to investigate the long-term effects on metabolism and body composition of oestrogen-progestagen (OP) compounds, which are frequently used in these women to treat hyperandrogenism and related clinical features. DESIGN: Long-term follow-up study. SUBJECTS AND METHODS: Thirty-seven women with PCOS were re-evaluated 10.3 +/- 0.8 years (range 6-18 years) after their first assessments (age: before 19.8 +/- 4.9 years; after 29.9 +/- 4.4 years). When first examined, women were instructed to follow a hypocaloric diet if they were obese plus OP, if they agreed to such treatment. Main anthropometric parameters, basal sex hormones and lipids, fasting and glucose-stimulated glucose and insulin levels and several clinical data were recorded before and after follow-up. RESULTS: In the whole group of women with PCOS we found no changes in body weight and fat mass, whereas both the waist-to-hip ratio and the waist-to-thigh ratio were significantly reduced. No significant changes occurred in mean fasting and glucose-stimulated glucose and insulin concentrations, whereas a significant increase in high-density lipoprotein-cholesterol was found. No significant changes occurred in testosterone levels. During the follow-up period 16 women took OP for an average of 97 +/- 18 months (range 12-180 months) (OP-users) whereas 21 women never took OP (non-OP-users). All OP-users were still taking OP when re-evaluated at the follow-up examination. With respect to baseline values, body mass index was higher in non-OP-users than in their counterparts. Waist circumference (P < 0.025), the waist-to-hip (P < 0.05) and the waist-to-thigh (P < 0.01) ratios decreased significantly only in the OP-users. In addition, percentage changes in waist circumference (P < 0.05) and waist-to-hip ratio (P < 0.05) during the follow-up period were significantly different between the groups. Glucose tolerance (as area under the curve (AUC)) improved (P < 0.05) in OP-users but not in non-OP-users. Moreover, compared to baseline values, basal insulin levels were significantly (P < 0.01) reduced in OP-users but not in non-OP-users. On the contrary, no significant change was found in insulinAUC in the former, whereas it significantly increased (P < 0.05) in the latter. Accordingly, fasting C-peptide decreased (P < 0.05) in OP-users, whereas both fasting (P < 0.01) and stimulated (P < 0.01) C-peptide significantly increased in non-OP-users. Changes in fasting or stimulated insulin and C-peptide in non-OP-users were not associated with parallel changes in testosterone levels. Total cholesterol and triglycerides did not change in either group, but HDL-cholesterol increased (P < 0.05) only in OP-users. Sex hormone-binding globulin concentrations increased significantly (P < 0.01) in OP-users, without any significant change in non-OP-users. Testosterone concentrations did not change significantly in either group, but the testosterone: SHBG ratio significantly decreased in OP-users (P < 0.05) but not in the non-OP-users. Among the clinical features, acanthosis nigricans significantly (P < 0.01) worsened in non-OP-users but not in the OP-users, without any significant change in the hirsutism and acne scores. Pregnancy rates during the follow-up were similar in both groups. CONCLUSIONS: These data indicate that hyperinsulinaemia and insulin resistance tended to worsen spontaneously in women with PCOS, without any worsening of the hyperandrogenism. Long-term oestrogen-progestagen treatment countered this tendency, probably because it improved the pattern of body fat distribution, by reducing abdominal fat depots.

Adolescent↗
PubMed1998

Serum leptin in obese women with polycystic ovary syndrome is correlated with body weight and fat distribution but not with androgen and insulin levels.

Leptin is a hormone produced in the adipose tissue and its concentrations in peripheral blood are significantly correlated with the amount of body fat. Whether other factors, including the pattern of body fat distribution and several hormones (such as insulin, sex steroids, and glucocorticoids), may be involved in the regulation of circulating blood leptin levels is controversial. Women with the polycystic ovary syndrome (PCOS) are hyperandrogenic and most of them are characterized by hyperinsulinemia, insulin resistance, and obesity, particularly the visceral phenotype. To assess the potential contribution of anthropometric factors, androgens, and insulin in determining leptin levels, we examined their relationship with body-mass index (BMI), visceral (VAT) and subcutaneous (SAT) adipose tissue areas, basal androgen levels, and fasting and glucose-stimulated (AUC) insulin in different groups of obese women with PCOS (n = 23) and of age-matched obese (n = 16) and non-obese (n = 10) otherwise healthy controls. The VAT/SAT ratio was measured as a parameter of body fat distribution. Serum leptin levels were significantly higher in obese PCOS women than in obese and normal-weight healthy controls and, within the controls, in the obese than in the non-obese group. In all women considered together, and in each group separately, leptin concentrations were highly significantly correlated with BMI. In addition, after adjusting for BMI, both VAT and the VAT/SAT ratio were positively and significantly correlated with leptin. Partial correlations with the VAT/SAT ratio remained significant in both the obese PCOS group and in controls considered separately, whereas the correlation with the SAT value was significant only in the control group. After adjusting for BMI, no correlation between leptin, androgens and fasting or stimulated (like AUC) insulin was found. These findings indicate that leptin levels in obese women with PCOS are higher than those observed in obese and non-obese controls. Moreover, they suggest that, other than BMI, the pattern of body fat distribution may be an independent factor related to circulating leptin levels, which, on the contrary, do not appear to be related to either androgen or insulin concentrations.

Adipose Tissue↗
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↗