Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological and biological data on HRT and breast cancer risk are reviewed. Some aspects deserve consideration. (1) The majority of epidemiological data have been gathered from populations where high estrogen doses (> or = 1.25 mg daily of conjugated estrogens) were used as first line therapy. (2) HRT does not increase the risk in overweight women, even in the series in which a risk increase (in longterm users) is found. This could be as a result of the fact that oral estrogens, through their metabolic and hepatocellular effects, reverse some biological features of obesity (e.g. increased insulin-like growth factor I activity and decreased sex hormone binding globulin level) which potentially increase breast cancer risk, so balancing the estrogen stimulation. (3) The progestin addition seems to increase the risk when the 19 nor-testosterone derivatives are used. These androgenic compounds contrast the metabolic and hepatocellular effects of oral estrogens. To sum up, the possibility does exist that even the longterm use of oral estrogens at the right ('low') dose, with the addition of a non-androgenic progestin, will be shown to be associated with a very limited breast cancer risk increase.
 ...
PMID:HRT and breast cancer risk: a clue for interpreting the available data. 1065 96

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.
 ...
PMID:The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome. 1138 73

Obesity, the result of combined genetic and environmental factors, is in recent decades one of the most frequent diseases and is encountered mainly in Europe and North America. In women it is associated with the risk of several diseases, such as diabetes mellitus, osteoarthritis, cardiovascular diseases, sleep apnoea syndromee, breast cancer, cancer of the uterus and also with impairment of reproductive functions. Already during the last century some observations confirmed that a very low or very high body weight is more frequently associated with disorders of the menstrual cycle (MC), infertility and poor reproductive capacity. However only during the last decades the pathophysiological and molecular mechanisms of this relationship were gradually elucidated. The main factors which influences the menstrual cycle in obesity are: impaired estrogen metabolism, changes in the concentration of sex hormone binding globulin, hyperinsulinaemia, and probably also leptin levels.
 ...
PMID:[Obesity and disorders of the menstrual cycle]. 1206 Nov 86

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.
 ...
PMID:Obesity and the polycystic ovary syndrome. 1208 Apr 40

Although a critical mass of adipose tissue is essential for the normal development of female reproductive function, obesity has been shown to produce menstrual disturbances and subfertility. The severity of obesity and the distribution of fat tissue are important factors that influence the female reproductive system. The pathogenetic mechanistic links between them aren't clearly elucidated. Obese women, especially those with upper body obesity, have insulin resistance and hyperinsulinaemia, hyperandrogenaemia, increased peripheral aromatization of androgens to oestrogens, altered gonadotrophin secretion, decreased sex hormone binding globulin, decreased growth hormone (GH) and insulin like growth factor binding proteins (IGFBPs), increased leptin levels and altered neuroregulation of the hypothalamic-pituitary-gonadal axis. These have been considered as some of the links in the sequence of events of the disrupted ovulatory process. The mechanisms of these actions and their influence on female reproductive function are discussed below.
 ...
PMID:The influence of obesity on hyperandrogenism and infertility in the female. 1211 94

Hyperandrogenemia and low levels of sex hormone binding globulin (SHBG) are frequently found in women with metabolic syndrome, which is characterized by low high-density lipoprotein cholesterol, hypertriglyceridemia, obesity, and hyperinsulinemia. The specific contribution of these various factors to coronary heart disease (CHD) is controversial. The coronary angiograms of 87 consecutive postmenopausal women were evaluated using 2 semiquantitative scoring systems to estimate the extent of focal and diffuse vessel wall alterations. Fasting sera were analyzed for levels of glucose, lipids, insulin, leptin, dehydroepiandrosterone sulfate, testosterone, and SHBG. Obesity was assessed by measuring body mass index, waist-to-hip ratio, skinfold thicknesses, and body impedance. After adjusting for age, there were significant differences in 55 women with CHD compared with 32 women without CHD: higher levels of low-density lipoprotein cholesterol (159 +/- 51 vs 132 +/- 39 mg/dl), apolipoprotein B (121 +/- 33 vs 102 +/- 29 mg/dl), triglycerides (115 vs 91 mg/dl), and basal insulin (7.5 vs 4.6 mU/L), as well as lower levels of high-density lipoprotein cholesterol (59.9 +/- 18.0 vs 69.0 +/- 17.1 mg/dl), SHBG (44.6 vs 68.1 nmol/L) and the quantitative insulin sensitivity check index (0.66 +/- 0.41 vs 0.93 +/- 0.73). Multivariate analysis by logistic regression identified age (odds ratio [OR] 1.22, 95% confidence intervals [CI] 1.09 to 1.37), smoking (OR 11.46, 95% CI 2.56 to 51.39), SHBG (OR 0.98, 95% CI 0.96 to 0.99), and apolipoprotein B (OR 1.02, 95% CI 1.01 to 1.04) as independently associated with the presence of CHD. Thus, low plasma levels of SHBG are associated with CHD in women independently of insulin, obesity markers, and dyslipidemia.
 ...
PMID:Relation of serum levels of sex hormone binding globulin to coronary heart disease in postmenopausal women. 1216 Dec 23

Data on hormone replacement therapy and breast cancer risk come from a number of observational studies (mostly American studies). Those published up to 1995 were reanalyzed by the Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC). They involved populations where exceedingly high estrogen doses were used as first-line therapy, and a progestin was added in a minority of women. Overall, the CGHFBC reanalysis found that the relative risk increased by 0.023 for each year of use (with an absolute excess risk of two or six cases out of 1000 women treated for 5 or 10 years, respectively). Further American studies, published in 2000 and involving populations where lower doses were used, showed a risk increase of 0.01 per year of estrogen-only use. Both the CGHFBC reanalysis and the further studies did not find an increase of risk in treated overweight women. Possibly, overweight women already have a maximal estrogenic stimulus on the breast due to extraglandular estrogen production. An additional explanation could be that oral estrogens, through their hepatocellular effects, reverse some biological features of obesity (e.g. decreased sex hormone binding globulin level and increased insulin-like growth factor-I bioactivity) that potentially increase breast cancer risk, so balancing the estrogen stimulation. The CGHFBC reanalysis did not show a substantial difference in breast cancer risk between the majority using estrogen alone and the small minority using estrogen plus progestin. Conversely, Swedish studies and the recent American studies suggest that the risk increase could be higher with the addition of a progestin, compared with estrogen-only use. The biological effect of progesterone/progestins on the breast tissue is controversial. Even if the observed increase in risk could be partially ascribed to non-progesterone-like effects of some progestins (e.g. opposing the hepatocellular effects of oral estrogens) and also (in the American studies) to use-bias, a detrimental action due to progesterone-like effects cannot be excluded. However, the theoretical possibility exists that low doses of oral estrogens, plus a progestin providing progesterone-like effects only, will be shown to be associated with a limited breast cancer risk increase.
 ...
PMID:Breast cancer and hormone replacement therapy: putting the risk into perspective. 1222 87

In young women being overweight appears to be one of the major and still neglected causes of subfertility. Not only the excessive amount but also the distribution of body fat is clearly related to loss of fertility. The mechanism through which obesity impairs ovulation and fertility is largely unknown, but it is well known that being overweight lowers the concentration of sex hormone binding globulin and increases androgen and insulin secretion and insulin resistance. These high concentrations of androgen and insulin in turn are important factors in the preferential abnormal localization of body fat. In addition, ovulation induction or ovarian stimulation in overweight women is a not easy task, since these patients are often unresponsive to the stimulatory drugs and, in addition, have a higher rate of miscarriages. Weight reduction improves these patients' biochemical indices and fertility rates. The spontaneous pregnancy rate can be expected to be around 30%, but an additional 40-50% drug-induced pregnancy rate can be achieved with a 10-15% weight loss. Drugs increasing insulin sensitivity also improve spontaneous ovulation and fertility in obese women but still need to be tested in larger controlled trials. In conclusion, appropriate counselling about weight reduction through diets and exercise can restore both health and fertility, avoiding much frustration, and saving time and money.
 ...
PMID:Resumption of fertility with diet in overweight women. 1241 30

It has been shown that prolactin (PRL) induces glucose intolerance, hyperinsulinemia and insulin resistance in several animal species. In women with microprolactinomas, the sensitivity to insulin is lower in hyperprolactinemia than in normoprolactinemia. Thirty non-obese women with hyperprolactinemia and 30 healthy non-obese women were included into the study. Age, body weight (bw), height, body mass index (BMI), waist circumference, hip circumference and waist to hip ratio of both patients with hyperprolactinemia and control subjects were not different. Mean serum prolactin level was higher in hyperprolactinemic patients than in control group (84.5 +/- 51.1 ng/ml and 13.8 +/- 5.3 ng/ml respectively, p<0.002). Mean HOMA-(%B) index of hyperprolactinemic patients was higher than in control subjects (121 +/- 49 and 84 +/- 38, respectively, p<0.02). Mean HOMA-(%S) index was lower in hyperprolactinemic patients (56 +/- 39 and 105 +/- 55, respectively, p<0.006). Serum total testosterone, free testosterone, androstenedione, estradiol, cortisol, sex hormone binding globulin and DHEA-S levels in both hyperprolactinemic women and healthy subjects, statistically did not show any difference between the two groups. The present data indicate that hyperprolactinemia is associated with an insulin-resistant state. This resistant state may not be a result of obesity, androgenic hormones, and SHBG or pregnancy. It may be the result of serum free fatty acids (FFA) levels, decrement in the number of insulin receptors (by a down-regulation of insulin receptors) or post-binding defect in insulin action or more.
 ...
PMID:Insulin sensitivity and hyperprolactinemia. 1284 42

Type 1 diabetes (with predominant insulin deficiency) was until recently assumed to be the diagnosis of almost all children presenting with glucose intolerance. This requires insulin treatment via subcutaneous injections, and most patients develop microvascular and macrovascular complications in adulthood. Advances in genetics in the 1990s identified a group of genetic disorders of pancreatic beta-cell function (maturity-onset diabetes of the young) for which the outlook is better than type 1, genetic testing is available, and oral medication is the preferred treatment. In 2000, the first cases of type 2 diabetes (predominant insulin resistance) were reported in UK children, reflecting a trend seen in North America over the last 20 years. Affected children are usually overweight or obese, often female, pubertal, predominantly of ethnic minority (South Asian) origin and have a family history of type 2 diabetes. The diagnosis is aided by demonstration of insulin resistance, and may include measurement of fasting insulin and C-peptide, markers of the metabolic syndrome (fasting lipids, sex hormone binding globulin) and absence of autoantibodies against beta-cell components (e.g. glutamic acid decarboxylase). Management is aimed towards weight stabilization in the growing child, education on healthy lifestyles and the treatment of hyperglycaemia with both insulin and insulin-sensitizing agents. The underlying cause of type 2 diabetes in children is likely to be related to the epidemic of childhood obesity. There is emerging evidence of an appalling outlook for these young people in terms of miscarriages and microvascular and cardiovascular complications, which are likely to present an enormous economic and health services burden over the next 20 years.
 ...
PMID:The emergence of type 2 diabetes in childhood. 1471 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>