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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the clinical importance of leptin's intraovarian effects, we studied the concentration of leptin and leptin binding activity in the plasma and in the follicular fluid of PCOS patients (n=20; median BMI: 27.1 kg/m2, range 19.7-36.3) undergoing controlled ovarian stimulation with long-term GnRH agonist, recombinant FSH, and in vitro fertilization. Follicular fluid and blood samples were collected during follicle aspiration for IVF. Total leptin concentration was measured by radioimmunoassay, and specific leptin binding activity was accessed by a gel filtration column assay. Follicular fluid and plasma leptin levels were similar (median 1135 pmol/l vs. 1409 pmol/l; p=0.81). Follicular fluid to plasma leptin ratio was independently associated with cumulative FSH dose (r=0.63; p=0.006) and insulin resistance index (r=-0.45; p=0.04). Specific leptin binding activity was higher in the plasma than in the follicular fluid [median 7.94% vs. 3.49%; p<0.001]. When multivariate analysis was used to predict FSH consumption, only follicular fluid leptin levels were significantly associated with cumulative FSH dose (r=0.46; p=0.04). We infer that at least in part by increased intrafollicular leptin levels, obesity directly affects ovarian function in PCOS, and may induce a relative resistance to gonadotropin stimulation. This intraovarian effect of leptin can be even more profound because of low leptin binding activity in the preovulatory follicle of obese patients.
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PMID:Leptin and leptin binding activity in the preovulatory follicle of polycystic ovary syndrome patients. 1121 47

The impact of insulin resistance on the outcome of IVF or intracytoplasmic sperm injection (ICSI) in women with polycystic ovarian syndrome (PCOS) was examined. Insulin sensitivity was measured by the continuous infusion of glucose with model assessment (CIGMA) test. Insulin-resistant (n = 26) and non-insulin-resistant women (n = 30) with PCOS underwent a total of 100 cycles of long-term down-regulation with buserelin acetate, stimulation with human recombinant FSH, and IVF or ICSI. Blood samples were taken throughout ovarian stimulation for hormone assays. Insulin-resistant and non-insulin-resistant women had similar concentrations of FSH, LH, testosterone and androstenedione throughout stimulation, but insulin-resistant women had hyperinsulinaemia and lower sex hormone binding globulin concentrations. Insulin-resistant women also had lower oestradiol concentrations during stimulation and required higher FSH doses, but these differences disappeared after controlling for the higher body weight in the group of insulin-resistant women. Groups had similar number of oocytes collected, similar implantation and pregnancy rates, and the incidence of ovarian hyperstimulation syndrome was also similar. Obesity, independent of hyperinsulinaemia, was related to a lower oocyte count and increased FSH requirement. It is concluded that in PCOS women receiving long-term down-regulation and stimulation with recombinant FSH, insulin resistance is neither related to hormone levels nor to IVF outcome. Obesity, independent of insulin resistance, is associated with relative gonadotrophin resistance.
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PMID:The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome. 1138 73

The paper concerns the treatment results of 113 women with PCO-S by laparoscopic (102) and microlaparoscopic (11) ovarian electrocautery. All of them were qualified for operation on the basis of the following criteria: menstrual cycle disturbances (oligo-/amenorrhoea), anovulation, hirsutism, obesity, LH/FSH ratio > 2 and when more than 10 follicles of < 8 mm diameter are seen in the ovary under theca albuginea in USG examination. During the one year after operation these women were observed. In the first group (patients after laparoscopy) ovulation occurred in 86 (84%) and pregnancy in 54 (53%); accordingly in the second group (women after microlaparoscopy) ovulation occurred in 9 (83%) and pregnancy in 4 (45%). The treatment results by microlaparoscopic and laparoscopic ovarian electrocautery are similar, but the method by microlaparoscopy is easier to carry out in selected cases.
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PMID:[The effects of micro-laparoscopic ovarian electrocautery as a method of polycystic ovary syndrome treatment]. 1159 50

The biological effects of hormones are mediated by plasma membrane receptors which transmit extracellular signals to the cytoplasm and nucleus. Mutations in plasma membrane receptors can affect normal signal transduction with loss-of-function mutations leading to hormone resistance and gain-of-function mutations leading to constitutive activation of signaling pathways. The loss-of-function mutations leading to familial hormone resistance disorders are germline in origin whereas the gain-of-function mutations leading to constitutively active receptors are somatic. G-protein coupled receptors (GPCR) comprise a large superfamily of proteins characterized by seven transmembrane-spanning segments and interaction with GTP-binding(G) proteins. Mutations in GPCRs have been associated with dwarfism, congenital hyperthyroidism or hypothyroidism, nephrogenic diabetes insipidus, obesity, resistance to TSH, LH, FSH and ACTH, Jansen's metaphyseal and Blomstrand's chondrodysplasia, autosomal dominant hypoparathyroidism, and neonatal severe hyperparathyroidism. Mutations in other families of receptors which are characterized into one spanning-transmembrane receptor can result in resistance to insulin, GH, leptin and AMH. This review summarizes the molecular defects in plasma membrane hormone receptors in a large number of clinical disorders.
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PMID:[Molecular defects in plasma membrane hormone receptors]. 1185 9

Hyperinsulinaemia and insulin resistance are usually associated phenomena of obesity and the polycystic ovary syndrome (PCO syndrome). On the other hand the PCO syndrome and obesity are often associated with disorders of the menstrual cycle and/or sterility. The authors examined 35 women aged 21 to 38 years (x = 27 +/- 4.4) with a history of anovulation cycles and/or sterility. 24 of them (68.6%) suffered from PCO syndrome. Their mean BMI was 28.95 kg/m2. 11 patients had a normal body weight, 6 were overweight and 18 were obese. The authors used the oral glucose tolerance test (oGTT) and during minute 0 and 120 blood samples were collected for assessment of the blood sugar and plasma insulin. Insulin levels in minute 0 (Io above 20 and in minute 120 (I120) above 65 uIU/ml were classified as hyperinsulinaemia. In the follicular stage of the anovulation cycle the authors assessed FSH, LH, testosterone, progesterone and prolactin. Hyperinsulinaemia ws recorded in 16 of 35 women. The mean insulin level at minute 0 was 11.9 +/- 1.3 and during minute 120 54.2 +/- 8.1 uIU/ml. The authors found significant differences in levels of I0 (6.4 +/- 1.2 vs. 16.1 +/- 1.9 uIU/ml, p < 0.01) and I120 (17.5 +/- 3 vs. 71.3 +/- 10.3 uIU/ml, p < 0.01) between obese and non-obese patients, Also in patients with the PCO there was a statistically significant difference in insulin levels of slim (BMI less than 25) as compared with obese women (BMI more than 30) (p < 0.01). A positive correlation was found between insulin levels and BMI (p < 0.01) and a liminal correlation between insulin and testosterone (p = 0.05). Patients with hyperinsulinaemia were treated with oral antidiabetics from the group of biguanides--metformin for a period of three months. During metformin treatment the insulin level declined and subsequently the menstrual cycle became normal in 11 of 16 patients with hyperinsulinaeia (68.7%), incl. two women who became pregnant. The results indicate a possible new indication of metformin in the treatment of ovarian hyperandrogenism in insulin resistant patients.
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PMID:[Hyperinsulinemia and disorders of the menstrual cycle]. 1196 79

We report a 28-year-old-female who presented with primary amenorrhoea, absence of puberty, obesity and normal stature. The subject was clearly short as a child, with a height more than 2 SD below normal until the age of 15 years. The pubertal growth spurt failed to develop. She continued growing at a prepubertal rate until growth ceased at the age of 20 years, reaching her final adult height of 157 cm (SDS -0.86) without hormonal treatment. A combined pituitary hormone stimulation test of anterior pituitary function showed deficiencies of GH, LH and FSH, and low normal serum levels of TSH and PRL. Magnetic resonance imaging revealed a hypoplastic pituitary with markedly reduced pituitary height. In addition, a whole body dual energy X-ray absorptiometry scan showed high levels of body fat (54%). Combined pituitary hormone deficiencies with a hypoplastic pituitary suggested the diagnosis of a Prophet of Pit-1 (PROP1) gene mutation. Normal stature in this case, however, confounded this diagnosis. Sequencing of PROP1 revealed homozygosity for a single base-pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop-1 protein. To our knowledge, this is the first report of a patient with a mutation in the PROP1 gene that attained normal height without hormonal treatment, indicating a new variability in the PROP1 phenotype, with important implications for the diagnosis of these patients. We suggest that this can be explained by (i) the presence of low levels of GH in the circulation during childhood and adolescence; (ii) the lack of circulating oestrogen delaying epiphyseal fusion, resulting in growth beyond the period of normal growth; and (iii) fusion of the epiphyseal plates, possibly as a result of circulating oestrogens originating from peripheral conversion of androgens by adipose tissue.
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PMID:A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty. 1215 92

Girls with premature adrenarche (PA), similar to women with polycystic ovarian syndrome, display alterations in the IGF system, may have impaired insulin sensitivity, and demonstrate unfavorable lipid profiles. Girls with PA are also at increased risk for functional ovarian hyperandrogenism. Metabolic studies in boys with PA, however, are limited. The objective of this study was to determine whether boys with PA show alterations in insulin sensitivity and the IGF system. We studied an ethnically heterogeneous group of 19 prepubertal boys: 11 with PA (age, 8.2 +/- 0.7 yr; body mass index (BMI)-Z score, 1.8 +/- 1.1) and 8 controls (age, 7.9 +/- 0.8 yr; BMI-Z score, 1.2 +/- 1.0). Fasting levels of glucose, insulin, proinsulin (P(0)), hemoglobin A1c, testosterone, SHBG, delta4-androstenedione, dehydroepiandrosterone sulfate, LH, FSH, IGF-I, IGF-binding protein-1, IGF-binding protein-3, free IGF-I, and lipids were measured. Ten of 11 boys with PA and six of eight controls underwent standard oral glucose tolerance testing. The insulin response to this test was measured by the insulin area under the curve. Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. All values were adjusted for BMI-Z score. Total IGF-I, P(0), ratio of P(0) and fasting insulin level, and log insulin area under the curve were higher, and SHBG was lower in the boys with PA, compared with controls. Decreased insulin sensitivity was suggested by decreased composite insulin sensitivity index. A trend toward greater triglycerides was observed in the boys with PA, compared with the controls. Prepubertal boys with PA show differences in the IGF system and decreased insulin sensitivity, independent of obesity, as observed in girls with PA. These findings suggest that both boys and girls with PA should be monitored for the development of insulin resistance and associated complications, including diabetes mellitus and cardiovascular disease.
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PMID:Insulin sensitivity and the insulin-like growth factor system in prepubertal boys with premature adrenarche. 1246 59

Mono-ovulatory cycles for women are optimal because singleton pregnancies have a better outcome than multiples. Multiple births began to increase in the 1950s after the first appearance of effective ovulation induction for the treatment of anovulation. Since the 1980s when ovulation induction and IVF were more broadly applied to the treatment of unexplained and persistent infertility, there has been an unprecedented rise in multiple births. Strategies to achieve mono-ovulation during treatment of anovulatory patients are distinct from those for the treatment of ovulating patients who have unexplained and persistent infertility. Anovulatory patients with hypogonadotrophic hypogonadism can be treated with exogenous pulsatile GnRH, which restores normal gonadotrophin secretion, ovulation rates and conception rates. The multiple pregnancy rate is not increased with GnRH treatment. In patients with normogonadotrophic anovulation, attention should be given to diet and exercise before any other interventions are considered. Pharmacological induction of ovulation can be achieved with antiestrogen, gonadotrophin or pulsatile GnRH treatment; antiestrogen is the first choice with gonadotrophin more widely used for clomiphene citrate (CC)-resistant patients. Obesity and polycystic ovaries are common in this group, so that gonadotrophin and GnRH treatment are associated with lower responses compared with hypogonadotrophic hypogonadism, and higher multiple pregnancy rates. Low dosage protocols are being tested that may lower the multiple birth rates. The role of drugs enhancing sensitivity to insulin, e.g. metformin, remains undetermined. Laparoscopic ovarian diathermy achieves conception rates that are equivalent to gonadotrophin treatment, with fewer multiple births. Augmenting normal ovulation processes for couples with unexplained and persistent infertility is less effective. Pregnancy rates are statistically significantly higher with CC but the size of the increase is not clinically important. CC with intrauterine insemination is associated with a clinically important effect on conception. Achieving mono-ovulation is more difficult in assisted reproductive technology cycles because success depends on maintaining the level of FSH above the threshold level longer than normal in order to increase the number of mature follicles. Milder stimulation for IVF and IVF in the untreated cycle show great potential, however, especially in view of the trend toward transfer of a single embryo in assisted reproductive treatment cycles.
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PMID:Mono-ovulatory cycles: a key goal in profertility programmes. 1285 47

This follow-up study represents IVF treatment characteristics and outcomes in women with World Health Organization (WHO) group 2 anovulatory infertility after previous unsuccessful ovulation induction compared with controls. Furthermore, the possibility of initial screening parameters of these anovulatory women to predict IVF outcome was examined. Twenty-six patients with WHO 2 anovulatory infertility who failed to achieve a live birth following previous induction of ovulation (using clomiphene citrate as first line and exogenous FSH as second line) were compared with 26 IVF patients with tubal infertility matched for age, treatment period and treatment regimen. The WHO 2 patients underwent 49 IVF cycles, whereas the normo-ovulatory controls underwent 46 cycles. In WHO 2 patients 15 cycles were cancelled compared with six cycles in controls (P = 0.04). Cycles were predominantly cancelled due to insufficient response (P = 0.04). In cases in whom the cycle was cancelled, body mass index (BMI) was significantly higher (P < 0.001) in WHO 2 women compared with controls. Overall live birth rates were comparable (P = 0.9). Obese women suffering from WHO 2 anovulatory infertility are at an increased risk of having their IVF cycle cancelled due to insufficient response. Once oocyte retrieval is achieved, live birth rates are comparable with controls.
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PMID:IVF outcome in anovulatory infertility (WHO group 2)--including polycystic ovary syndrome--following previous unsuccessful ovulation induction. 1293 May 74

Albright hereditary osteodystrophy (AHO) is a genetic disorder caused by heterozygous inactivating mutations in GNAS1, the gene encoding the alpha-chain of G(s), and is associated with short stature, obesity, brachydactyly, and sc ossifications. AHO patients with GNAS1 mutations on maternally inherited alleles also manifest resistance to multiple hormones (e.g. PTH, TSH, LH, FSH), a variant termed pseudohypoparathyroidism (PHP) type 1a, due to paternal imprinting of G alpha(s) transcripts in specific tissues. Recent evidence has shown that G alpha(s) transcripts are also imprinted in the pituitary somatotrophs that secrete GH. Because this imprinting could influence GHRH-dependent stimulation of somatotrophs, we hypothesized that maternally inherited GNAS1 mutations would impair GH secretion. We studied GH status in 13 subjects with PHP type 1a. GH responses to arginine/L-dopa and arginine/GHRH were deficient in nine subjects, all of whom were obese and had low serum concentrations of IGF-I. By contrast, none of the four GH-sufficient subjects were obese, and all had normal IGF-I levels. Our data indicate that GH deficiency is common (69%) in PHP type 1a and may contribute to the obesity and short stature typical of AHO. We propose that GH status be evaluated in all patients with PHP type 1a.
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PMID:Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance. 1297 Feb 61


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