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

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. It is characterized by hyperandrogenism, chronic anovulation and it is often associated with hyperinsulinemia, insulin resistance and dyslipidaemia. The pathophysiology of polycystic ovary syndrome seems to implicate primary defects in ovarian steroidogenesis, influenced by environment, insulin action and obesity. Polycystic ovary syndrome is probably both a multigenetic and environmental disease. Knowing the genes of polycystic ovary syndrome would be helpful to develop therapeutics and prevention. Genes of gonadotrophins, steroid hormone synthesis and insulin resistance seem not to be directly involved, except perhaps the CYP 11 a gene. On the other hand, identification of the signal transduction pathways involved in these genes may provide valuable information that can be applied to other clinical manifestations of polycystic ovary syndrome (follicular growth arrest, insulin resistance, obesity and endometrial cancer...).
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PMID:[Polycystic ovary syndrome: recent genetic contributions]. 1219 44

Obesity is associated with considerably reduced plasma GH concentrations, which may contribute to anovulation in (obese) women with polycystic ovary disease (PCOS). This clinical investigation was undertaken to establish whether the GH release process is deranged in obese women with PCOS and, if so, whether the observed anomalies are features of the syndrome or a sequel of body fat accretion. To this end we sampled 24-h plasma GH concentration profiles at 10-min intervals in 15 obese PCOS patients [mean age, 29 yr (range, 20-38); percent body fat, 47 +/- 5.2%], 15 equally obese controls with regular menstrual cycles [age, 34 yr (range, 20-44); percent body fat, 48 +/- 4.9%], and 15 healthy age-matched lean controls [age, 34 yr (range, 21-45); percent body fat, 29 +/- 9.0%]. Compared with lean controls, obese PCOS patients exhibited a greater than 60% reduction in basal and a greater than 75% reduction in pulsatile and total daily GH secretion due to a 2.7-fold attenuation of burst mass and a lesser (1.4-fold) slowing of GH pulse frequency. The mean +/- SEM number of statistically significant GH peaks was 13.9 +/- 1.2/24 h, the endogenous GH half-life was 14.1 +/- 0.4 min, basal GH secretion was 5.0 +/- 0.7 mU/liter.24 h, and total secretion was 61.4 +/- 9.6 mU/liter.24 h in obese women with PCOS. None of these parameters differed from those in the body mass index-matched controls. The approximate entropy ratio was significantly increased in obese women (both PCOS and controls), indicating greater irregularity of the GH release process. Total GH secretion in patients and the two control groups correlated strongly and negatively with percent body fat (r = -0.775; P < 10(-8)). Serum concentrations of IGF-I and IGF-binding protein-3 were higher in patients with PCOS than in obese controls (P = 0.03 and P = 0.02, respectively), but the IGF-1/IGF-binding protein-3 ratio was equivalent in all three study groups. In conclusion, the profoundly reduced and irregular GH release in obese women with PCOS appears to be a corollary of body fat accretion and not of the syndrome per se.
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PMID:Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome. 1221 75

The pathogenesis of breast cancer is Extensive tests isolate 3 distinct factors: genetic, hormonal and viral. Thus, the risk factor is increased 2-3 times by hereditary predisposition whereas (bilateral) ovariectomy, blocking production of ovarian hormones, reduces the risk by 10 times. Childbirth reduces the risk in reverse proportion to its frequency; however, less protection is afforded if not accompanied by lactation. Nulliparity was recognized as a risk factor in 1926, but recent studies have proven less conclusive. Also included as risk factors are the intake of fatty nutrients and obesity. Further indications include older age at 1st pregnancy, menstrual disorders, and a prolonged reproductive life as a result of precocious menarche and/or delayed menopause. The longer menopause is delayed, the greater the premenopausal period characterized by hyperestrinization, anovulation, and a modest production of progesterone. Metabolism of estrogens oriented towards more active metabolites compounds the risk factors. It has been impossible to verify an etiologic connection between estrogenic preparations administered during post-menopause and breast cancer. Oral contraceptives, in general, do not seem to pose any risk. A connection between prolactin and cancer has been demonstrated in rodents, but not in humans. Antiprolactin pharmaceuticals are capable of inducing regression of neoplasia, indicating a plausible, however unproven, active role of prolactin. Progesterone acting as an antiestrogen reduces the levels of cytoplasmic receptors, thus probably acting protectively. Basically, two approaches are possible for endocrine treatment of metastasized breast carcinoma: ablative surgery based on hormone deprivation (ovariectomy, suprarenalectomy, hypophysectomy) or additive therapy based on hormonal interference (estrogens, androgens, progestins, antiestrogens).
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PMID:[Hormonodependence and hormonosensibility of the gynecological neoplasias. III. The breast carcinoma]. 1228 88

Obesity is a risk factor for women in both pregnancy and contraception. Obesity per se does not cause sterility, but problems in gonadotropic function can arise during periods of rapid weight gain in bulimic episodes. Dysovulation is more common in such cases than amenorrhea. In established obesity, anovulation may occur, as demonstrated by the temperature curve and hormonal levels, but it is usually due to other factors such as ovarian polycystic syndrome or Cushing's syndrome. The main problems of obesity during pregnancy are carbohydrate metabolic disorders and hypertension. In 1 study, hypertension was found in 42.4% of pregnancies of obese women vs. 5.84% in controls; 22% of cases were severe, with blood pressure over 160/100. Carbohydrate metabolic difficulties were found in 11.8% of obese subjects vs. 1.2% of controls. The main consequence of maternal obesity on the child is macrosomy; occurring in 21.3% of births vs. 5.8% in controls. 5.1% of births to obese women are postmature vs. .7% in controls. The rate of cesareans for obese women is high. Improved fetal prognosis in pregnancies of obese women requires increased clinical surveillance for signs of hypertension or excessive weight gain and laboratory monitoring of glucose metabolism every month or even every 2 weeks. A sonogram should be done to detect macrosomy. A careful diet of 1200-1500 calories per day is recommended. 40% should be protein and 30% lipid. Rapid-absorption sugars should be excluded. Oral contraceptives appear to cause weight gain because estrogen stimulates the appetite and progestins have an anabolizing action. If weight gain exceeds 3 kg, a low dose pill and a restrictive diet should be recommended. OCs should be terminated if weight gain continues, and anomalies of glucose or lipid metabolism should be ruled out. Obesity constitutes a relative contraindication for use of combined OCs. Combined OCs may aggravate the obesity. Obesity on the other hand is a risk factor for cardiovascular accidents in OC users. IUDs are preferred for multiparous obese women. Nulliparas and multiparas with absolute contraindications to IUDs can use low-dose OCs if there are no other cardiovascular risk factors, no weight gain, and blood pressure and lipid and glucose metabolism are checked every 6 months. If these conditions cannot be met, the use of condoms or spermicides is recommended.
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PMID:[The obese woman: pregnancy and contraception]. 1228 89

Acne and hirsutism are common findings in girls with juvenile neuronal ceroid lipofuscinosis (JNCL). A study on their hormonal status was conducted to investigate the mechanisms underlying these symptoms. Sixteen girls with JNCL entered the study. Ten of the girls had periodic menstruation, while three were given medroxyprogesterone acetate therapy to prevent menstrual bleeding, and three had earlier undergone an ovariectomy. Ten age- and weight-matched healthy girls served as controls. Age at menarche, menstrual cycle length, acne, and hirsutism were assessed. Extensive hormonal laboratory tests were made in the early follicular phase. In addition, 1.5 Tesla magnetic resonance imaging of the lower abdomen was performed to search for structural abnormalities of the ovaries. The mean age at menarche in these JNCL patients was 11.6 years. Of the patients with periodic menstruation, four of ten had irregular (prolonged) cycles, but, in patients with regular cycles, the mean ovarian cycle was short (26 days). Hyperandrogenism, characterized by acne, hirsutism and/or hyperandrogenaemia, was found significantly more often in the patients than in the controls (p<0.01). No significant differences were found in the laboratory parameters. Polycystic ovaries were found in two of seven of the patients who menstruated, but in none of the healthy controls. Hyperandrogenism is common in patients with JNCL. In addition, there is an early menarche and signs of anovulation. The factors underlying these hormonal changes seem complex, possibly including a neurodegenerative process, the obesity associated with JNCL, and the drugs used for symptomatic treatment of the patients.
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PMID:Hyperandrogenism in girls with juvenile neuronal ceroid lipofuscinosis. 1237 86

Endometrial cancer is a disease of the affluent, developed world, where epidemiological studies have shown that > or =40% of its incidence can be attributed to excess body weight. An additional proportion may be because of lack of physical activity. Alterations in endogenous hormone metabolism may provide the main links between endometrial cancer risk, and excess body weight and physical inactivity. Epidemiological studies have shown increased endometrial cancer risks among pre- and postmenopausal women who have elevated plasma androstenedione and testosterone, and among postmenopausal women who have increased levels of estrone and estradiol. Furthermore, there is evidence that chronic hyperinsulinemia is a risk factor. These relationships can all be interpreted in the light of the "unopposed estrogen" hypothesis, which proposes that endometrial cancer may develop as a result of the mitogenic effects of estrogens, when these are insufficiently counterbalanced by progesterone. In our overall synthesis, we conclude that development of ovarian hyperandrogenism may be a central mechanism relating nutritional lifestyle factors to endometrial cancer risk. In premenopausal women, ovarian hyperandrogenism likely increases risk by inducing chronic anovulation and progesterone deficiency. After the menopause, when progesterone synthesis has ceased altogether, excess weight may continue increasing risk through elevated plasma levels of androgen precursors, increasing estrogen levels through the aromatization of the androgens in adipose tissue. The ovarian androgen excess may be because of an interaction between obesity-related, chronic hyperinsulinemia with genetic factors predisposing to the development of ovarian hyperandrogenism.
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PMID:Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. 1249 40

Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and affects approximately 4-7% of reproductive age women in the U.S. It is characterized by hyperandrogenemia and chronic anovulation and is associated with insulin resistance, obesity, and increased risk for type 2 diabetes. In a screen of candidate genes, a region on chromosome 19p13.3 was identified that shows significant evidence for both linkage and association with PCOS. A promising candidate gene for PCOS, resistin, maps to exactly this region. Resistin is a protein hormone thought to modulate glucose tolerance and insulin action. We tested for association between a single nucleotide polymorphism in the promoter region of the resistin gene and three phenotypes: PCOS, obesity, and insulin resistance. We did not find evidence for association with any of the phenotypes. It is therefore unlikely that variation in the resistin gene accounts for the strong association that we observe between chromosome 19p13.3 and PCOS. Instead, this association is most likely due to a gene or genetic element in this region that has not been identified.
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PMID:Variation in resistin gene promoter not associated with polycystic ovary syndrome. 1250 16

Polycystic ovary syndrome (PCOS) appears to be a lifelong disorder. The stigmata of insulin resistance, including obesity and premature adrenarche, may be early forms of its presentation. Girls with premature pubarche, characterized by elevated dehydroepiandrosterone levels and hyperinsulinemia, are at high risk for developing the full PCOS phenotype, including ovarian hyperandrogenism and chronic anovulation. Because PCOS is associated with a 40% prevalence of abnormal glucose tolerance, every adolescent patient should be evaluated regularly for glucose intolerance with a 2-hour oral glucose tolerance test and for lipid abnormalities with a fasting lipid profile. The role of insulin-sensitizing medications such as metformin in adolescents with PCOS is unclear; short-term studies suggest that these agents improve circulating androgens and ovulatory frequency. Primary prevention of diabetes mellitus and cardiovascular disease by lifestyle modification, including regular exercise and a balanced diet, is particularly important in adolescents, who have the opportunity to establish healthy habits before entering adulthood. The findings of diabetes prevention trials suggest that these interventions may be more efficacious than pharmacological therapy.
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PMID:Detection of insulin resistance and its treatment in adolescents with polycystic ovary syndrome. 1251 Sep 93

In mammals, the pleiotropic biological functions of tumor necrosis factor alpha (TNF-alpha) may include important effects on human reproductive physiology. Thus, chronic anovulation, oligo or amenorrhea, infertility, hyperandrogenism, obesity, insulin resistance and increased TNFalpha serum levels have been observed in women affected by polycystic ovary syndrome (PCOS). Whole blood short - term cell cultures (WBSC) are simple systems where the capacity to produce TNF-alpha by circulating leukocytes, mainly of the macrophage/monocyte lineage, can be accurately quantified. Given the relevance of monocytes/macrophages in the production of TNF-alpha, in this study, in a control-case approach, WBSC from women with PCOS were analyzed in their basal and lipolysaccharide (LPS)- stimulated capacity to produce the cytokine. These measurements did not correlate with the increased serum levels of the cytokine and the normal levels of cortisol, found in PCOS women. Increased serum TNF-alpha levels in PCOS women correlated positively with body mass index and negatively with insulin sensitivity. In spite of the increased serum TNF-alpha levels in PCOS women, basal and LPS stimulated production of the cytokine, by the ex vivo WBSC from these patients, were within normal values.
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PMID:Evaluation of tumor necrosis factor alpha production in ex vivo short term cultured whole blood from women with polycystic ovary syndrome. 1251 26

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases in women. This syndrome is characterized by hyperandrogenism, chronic anovulation, infertility and obesity. The association between PCOS-related hyperandrogenemia and insulin resistance is well documented in the literature. Insulin resistance and the resulting raised plasma levels of insulin are reported to be responsible for the high androgen concentration observed in patients with PCOS. In this prospective study, blood samples for levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH, prolactin and fasting blood sugar (FBS) before starting metformin administration were obtained randomly from 40 women who were apparently obese, had PCOS and had been referred to a university hospital. Metformin was then given at a dose of 500 mg three times a day for 8 weeks, after which time the pretreatment study was repeated. Clinical symptoms of PCOS, including acne and hirsutism score and body mass index (BMI), were assessed before and after the treatment cycle. Metformin therapy resulted in a significant decrease in total testosterone levels and FBS. There was also a significant decline in BMI, length of the menstrual cycle, acne and hirsutism score. There were no significant changes in the levels of DHEAS, prolactin, FSH or LH, or in LH/FSH. The effect of metformin on subjects with elevated DHEAS levels was different to that on individuals with normal DHEAS levels. In the latter group there were only significant improvements in the length of the menstrual cycle, BMI and testosterone and DHEAS levels. It is concluded that metformin therapy in subjects with PCOS results in a decrease in fasting blood sugar and testosterone levels, and leads to a significant improvement in the clinical manifestation of hyperandrogenism. These responses also related to the level of adrenal function.
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PMID:Effects of metformin therapy on hyperandrogenism in women with polycystic ovarian syndrome. 1272 19


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