Low AMH levels as a marker of reduced ovarian reserve in young women affected by Down's syndrome.

OBJECTIVE: Women with Down's syndrome (DS) experience menopause earlier than healthy women and are twice as likely to undergo premature ovarian insufficiency. Menopause accelerates cognitive decline and is associated with a twofold increased mortality risk in DS women. Nonetheless, no previous studies investigated the ovarian reserve in this population. The aim of the present study was to evaluate the circulating antimullerian hormone (AMH) levels in DS women with regular menstrual cycles, in comparison with those observed in an age-matched group of healthy women. METHODS: Fourteen women with DS and 20 normo-ovulatory volunteers were enrolled in this study. A general physical examination was performed. Hormonal assays, including AMH, fasting insulin levels, and homeostatic model assessment-insulin resistance, were investigated in all participants. RESULTS: AMH levels were significantly lower in DS women compared with controls (1.34 ±â€Š1.11 vs 3.01 ±â€Š1.65 ng/mL, P < 0.01). Prolactin concentrations were in the normal range, although higher in DS women compared with controls (P < 0.01). After dividing the participants according to age, AMH was significantly lower in the DS group compared with controls, both below and above 30 years of age (1.77 vs 3.73 ng/mL, P < 0.01; 0.28 vs 2.20 ng/mL, P < 0.01, respectively). AMH was inversely correlated with age in both groups, and directly correlated with testosterone and dehydroepiandrosterone sulfate only in DS women. In the same participants, AMH showed a tendency toward a direct correlation with insulin levels (P = 0.055). CONCLUSIONS: AMH levels were significantly lower in DS women compared with age-matched controls. A subanalysis of data in DS participants under 30 years of age suggested an early follicular depletion related to trisomy 21.

Fasting and post-methionine homocysteine levels in Alzheimers disease and vascular dementia.

The aim of the study is to compare the basal homocysteine levels in patients with impairment of cognitive status, and in controls, to evaluate if the methionine loading test is able to identify any differences between patients with Alzheimers disease and patients with vascular dementia. We enrolled 56 subjects, 20 with Alzheimers disease, 18 with vascular dementia, and 18 normal controls. The data shown that plasma homocysteine levels both basal and post-methionine load were significantly higher in the two groups of demented patients than in the control group. No significant differences were found between Alzheimers patients and vascular dementia patients. The homocysteine percent increase after a methionine loading test was significantly higher in the controls with respect to the two groups of demented patients. Only in Alzheimers patients were vitamin B(12) basal levels negatively correlated with basal homocysteine levels (p<0.05), while positively correlated with the homocysteine percent increase after load (p<0.05). The study confirms the possible role of chronically elevated homocysteinemia in neuronal degeneration in demented patients. Even if the methionine loading test revealed an abnormal homocysteine metabolism in demented patients, it didnt show any difference among patients with Alzheimers disease and vascular dementia.

Alteration of ghrelin-neuropeptide Y network in obese patients with polycystic ovary syndrome: role of hyperinsulinism.

OBJECTIVE: Insulin, ghrelin, neuropeptide Y (NPY) and leptin interact in the regulation of energy homeostasis. Most of these signals are altered in polycystic ovary syndrome (PCOS), which is characterized by a high prevalence of obesity. The present study was conducted to evaluate ghrelin-NPY and ghrelin-leptin interplays in relation to insulin secretion in obese PCOS subjects. DESIGN: Pilot prospective study. PATIENTS: Seven obese PCOS women and seven age-weight matched controls. MEASUREMENTS: Hormonal measurements, oral glucose tolerance test (OGTT) and a ghrelin test (1 microg/kg i.v. bolus). PCOS patients repeated the clinical work-up after 4 months of metformin treatment (1500 mg/day orally). RESULTS: At baseline, PCOS women showed a significantly higher insulinaemic response to the OGTT compared to controls (P < 0.05). In basal conditions, PCOS women exhibited lower NPY levels than controls (P < 0.01). Ghrelin injection markedly increased NPY in controls (P < 0.01), whereas PCOS women showed a deeply blunted NPY response to the stimulus (area under the curve--AUC-NPY: P < 0.01 vs. controls.). Metformin treatment induced a significant decrease in insulin levels (P < 0.01) and the concomitant recovery of NPY secretory capacity in response to ghrelin (AUC-NPY: P < 0.05 vs. baseline) in PCOS women. Leptin levels, which were similar in the two groups, were not modified by ghrelin injection; metformin did not affect this pattern. CONCLUSION: Hyperinsulinaemia seems to play a pivotal role in the alteration of NPY response to ghrelin in obese PCOS women. This derangement could be implicated in the physiopatology of obesity in these patients.

Metformin treatment does not affect total leptin levels and free leptin index in obese patients with polycystic ovary syndrome.

Leptin, particularly in its free form, is deeply involved in the regulation of energy balance. Insulin was suggested to influence plasmatic leptin levels and soluble leptin receptor in humans. However, this study indicates that metformin treatment, although improving insulin levels, does not exert a significant effect on either total leptin level or free leptin index in obese women with hyperinsulinemia and PCOS.

Free and total leptin serum levels and soluble leptin receptors levels in two models of genetic obesity: the Prader-Willi and the Down syndromes.

Alterations in energy balance and feeding behavior and the subsequent high frequency of obesity are hallmarks of 2 chromosomal diseases: the Prader-Willi syndrome (PWS) and the Down syndrome (DS). Leptin, an important regulator of food intake and energy homeostasis, circulates in 2 forms: a free, therefore active, fraction and a fraction bound to the soluble leptin receptor, whose bioavailability consequently participates in the regulation of leptin action. To investigate the possible role of the free-bound leptin balance in the pathogenesis of obesity in PWS and DS, we enrolled 7 obese women with DS, 5 obese women with PWS, 7 obese women, and 7 normal-weight healthy control women. Basal hormonal concentrations, total and free leptin levels, and leptin receptors levels were measured in plasma samples obtained from the 4 groups. No significant differences were observed in the hormonal milieu. Women with DS exhibited lower total leptin concentrations (P<.01), comparable leptin receptor level and, therefore, lower free leptin values (P<.01) when compared with obese controls, then resembling the profile peculiar to normal-weight control women. At variance, subjects with PWS did not differ from obese controls regarding both leptin and leptin receptor levels. Our data suggest that, whereas subjects with PWS have a leptin assessment corresponding to their degree of obesity, subjects with DS may have a defect in the secretion of leptin that could at least partially account for this form of syndromal obesity.

Association of thyroid dysfunction with vitamin B12, folate and plasma homocysteine levels in the elderly: a population-based study in Sicily.

BACKGROUND: Association of thyroid dysfunction with plasma homocysteine levels and vitamin B(12) has previously been reported. We evaluated these associations in the elderly in San Teodoro, a mountainous village of Sicily. METHODS: Subjects (n=279) aged 60-85 years (119 males and 160 females) were examined using self-reported signs, clinical examination and laboratory tests. RESULTS: Hypothyroidism and/or goiter were two characteristics that were not associated with a significant change in homocysteine when compared with euthyroidism and the absence of goiter. Vitamin B(12) was significantly higher in subjects in the first quartile of the thyroid-stimulating hormone distribution, compared with those in the fourth quartile (371+/-207 vs. 297+/-196 pmol/L, p=0.0121). Homocysteine was significantly higher in the first quartile of the free tri-iodothyronine distribution compared to the third quartile (18.0+/-5.7 vs. 16.0+/-6.2 micromol/L, p=0.0130) and was correlated with log tri-iodothyronine in euthyroid subjects (p=0.0254). In multivariate analysis, homocysteine was associated with vitamin B(12) (p=0.0014), folate (p<0.0001), creatinine (p<0.0001) and age (p<0.0001), but not with either free tri-iodothyronine (p=0.7680), tetra-iodothyronine (p=0.5706) or thyroid-stimulating hormone (p=0.2294). CONCLUSIONS: Our results suggest that the influence of thyroid hormones on homocysteine is much weaker in elderly subjects than in selected patients with hypothyroidism.

Plasma levels of neuropeptides in Alzheimer's disease.

BACKGROUND: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Indeed, previous studies have documented that glucagon-like peptide 1 (GLP-1) possesses neurotropic properties and can reduce amyloid-beta peptide levels in the brain in vivo. Moreover, the concentrations of neuropeptide Y (NPY) seem to be altered in the cerebrospinal fluid of patients with AD and in subjects with major depression. Finally, among the modifications induced by aging, a dysregulation of the ghrelin-growth hormone (GH) system has been reported. METHODS: We investigated the plasma concentrations of these neuropeptides in 14 subjects with AD. Data obtained from these patients were compared with data from an age- and weight-matched healthy group. RESULTS: No significant differences were found between the two groups in relation to plasma levels of GLP-1, NPY, ghrelin and GH. Peripheral NPY concentrations were positively correlated with ghrelin levels in both groups, and with plasma GLP-1 concentration only in controls. CONCLUSION: On the basis of our results, peripheral levels of these neuropeptides seem not to serve as biochemical markers of AD.