Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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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 (PCOS) is characterized by hyperandrogenism, chronic anovulation, and oligomenorrhea (O/M). PCOS has variable clinical phenotypes, biochemical features, and metabolic abnormalities. To determine the prevalence of PCOS in the Greek population as well as the metabolic parameters, we performed a cross-sectional study of 192 women of reproductive age (17-45 yr), living on the Greek island of Lesbos. They were divided into 4 groups according to the presence of hirsutism (defined as a Ferriman-Gallwey score > or = 6) and O/M: group N (n = 108), regular menses and absence of hirsutism; group 1 (n = 56), regular menses and hirsutism; group 2 (n = 10), O/M and absence of hirsutism; and group 3 (n = 18), O/M and hirsutism. Body mass index, waist to hip ratio, and mean blood pressure did not differ among the studied groups. Hormonal profile was assessed by measuring free testosterone (FT). The prevalence of PCOS, defined by the presence of O/M and biochemical hyperandrogenism (FT > or = 95th percentile of the normal women), was estimated to be 6.77% (13 women of 192). Higher FT levels were observed in group 3 (O/M and hirsutism) compared with groups N (P < 0.00001) and 1 (P < 0.0001) and in groups 1 (hirsutism) and 2 (O/M) compared with group N (P < 0.0001 and P < 0.005, respectively). Sex hormone-binding globulin levels were lower in women with PCOS and in groups 1 and 3 than those in group N (P < 0.002, P < 0.02, and P < 0.002, respectively) independently of the body mass index. The metabolic profile was investigated by measurements of fasting glucose (FG), fasting insulin (FI), and estimation of the fasting glucose to insulin ratio (FG:I ratio). After covariance adjusted for the BMI, FI levels were higher in group 3 and in women with PCOS than in the normal (P < 0.005 and P < 0.002, respectively) and the hirsute (P < 0.05 and P < 0.02, respectively) women, whereas FG levels did not differ among the studied groups. The FG:I ratio was lower in group 3, group 1, and in women with PCOS than in normal women (P < 0.05). Finally, a high incidence of family history of diabetes mellitus (P = 0.001) and menstrual disorders (P = 0.01) was observed in women with PCOS, in contrast to the normal and hirsute women. In conclusion, PCOS appears to be a particularly common endocrine disorder in the Greek population under study (prevalence, 6.77%); furthermore, it is associated with certain metabolic abnormalities. These data also suggest that the severity of the fasting hyperinsulinemia is associated with the severity of the clinical phenotype of hyperandrogenism independently of obesity.
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PMID:A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. 1056 41

Polycystic ovary syndrome (PCOS) is the most common disorder of ovarian function in premenopausal women. PCOS is characterised by chronic anovulation and androgen excess with clinical manifestation of irregular menstrual cycles, hirsutism and/or acne. Insulin resistance with resultant hyperinsulinaemia, irrespective of excess weight or frank obesity, has been reported in patients with PCOS, and, as insulin has a direct effect on ovarian androgen production in vitro, insulin resistance may play a crucial role in the physiopathology of PCOS. Although the molecular mechanism(s) of insulin resistance in PCOS is unclear, excessive insulin-independent serine phosphorylation of the beta subunit of the insulin receptor, as reported in some patients with PCOS, has been put forward as a new mechanism for insulin resistance. Insulin-sensitising agents have recently been investigated for their role in the short term treatment of insulin resistance in PCOS. Controlled studies have shown that metformin administration, by promoting bodyweight loss, can decrease fasting and stimulated plasma insulin levels. However, other studies have shown metformin 500 mg 3 times daily to decrease insulin secretion and to reduce ovarian production of 17alpha-hydroxyprogesterone with recovery of spontaneous or clomifene-induced ovulation, independently of weight loss. These findings suggest a new indication for metformin and present insulin-sensitising agents as a novel approach in the treatment of ovarian hyperandrogenism and abnormal ovulation in PCOS. They also suggest that long term administration of metformin might be helpful in treating insulin resistance, thus reducing risks of type 2 (non-insulin-dependent) diabetes and cardiovascular disease in these patients.
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PMID:Insulin resistance, polycystic ovary syndrome and metformin. 1057 24

Obesity, ultrasonic ovarian morphology, serum LH levels and LH/FSH ratio are inconstant symptoms of the polycystic ovary syndrome (PCOS) and are thus no longer essential for diagnosis. PCOS is diagnosed today by the finding of chronic anovulation and hyperandrogenism characterized by a high serum level of "free" testoterone. The other causes of hyperandrogenism, as well as anovulations due to hyperprolactinemia, high levels of FSH and abnormal thyroid function have to be ruled out. PCOS is very often associated with insulin resistance (IR) and hyperinsulinemia (hyper I). From in vitro and vivo studies and treatment of hyper I, it has been shown that the hyper I of PCOS stimulates androgen production. Hyper I of PCOS increases the activity of androgens: by first provoking an important decrease of the sex hormone binding globulin (SHBG) thus increasing the "free", bioactive testosterone level. and then by activating the cytochrome P 450 c 17 alpha enzymatic system that controls androgen production. Subsequent to metformin administration, the reduction of hyper I and androgen serum levels creates a favorable condition for the resumption of ovarian function and clomiphene citrate action. This explains the high percentage of ovulations and pregnancies.
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PMID:[Diagnosis and treatment of polycystic ovary syndrome]. 1059 43

Fifty patients with primary GH resistance (Laron syndrome) due to molecular defects of the GH receptor or post-receptor pathways were followed from infancy through adulthood. This condition leading to long-term insulin-like growth factor-I (IGF-I) deprivation caused marked growth retardation (-4 to 8 height SD), acromicia, organomicria, retarded development of the skeletal and muscular systems, a small cranium, slow motor development, and impairment of intellectual development in some of the patients. In addition, there was progressive obesity, insulin resistance, a tendency for hypoglycemia, followed later in life by hypercholesterolemia and by glucose intolerance and even diabetes. IGF-I treatment of children with Laron syndrome, by our and other groups (150-240 microg/day sc), stimulated growth (8 cm in the first year and 4-5 cm in the following years) and normalized the biochemical abnormalities. Overdosage led to adverse effects such as hypoglycemia, edema, swelling of soft tissues, and hyperandrogenism. It is concluded that primary IGF-I deprivation induces severe auxological, biochemical, and hormonal changes, the only treatment being biosynthetic IGF-I administration.
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PMID:The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome. 1059 94

Premature adrenarche was previously thought to be a benign condition. However, the authors and several other research groups have noted hyperinsulinism and insulin resistance in many girls with premature adrenarche. African-American and Caribbean-Hispanic girls with premature adrenarche are frequently obese with marked hyperandrogenism, signs which correlate with the degree of insulin resistance (i.e., those girls who are obese and insulin resistant tend to have higher levels of adrenocorticotropic hormone-stimulated androgens). Also, girls with premature adrenarche and reduced insulin sensitivity can have subtle decreases in their high-density lipoprotein (HDL) profile. Many of these girls have a strong family history of type 2 diabetes mellitus. Preliminary data regarding long-term follow-up of girls with premature adrenarche indicate that those girls who remain obese are at risk of developing polycystic ovary syndrome (PCOS). The term 'syndrome X' refers to the constellation of laboratory and clinical findings associated with hyperinsulinism stemming from insulin resistance. These findings include obesity, acanthosis nigricans, glucose intolerance, type 2 diabetes mellitus, dyslipidaemia with reduced HDL and elevated low-density lipoprotein, cardiovascular disease and PCOS. Hence, for certain girls, premature adrenarche may be a part of the clinical spectrum of syndrome X.
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PMID:Premature adrenarche: findings in prepubertal African-American and Caribbean-Hispanic girls. 1062 48

Polycystic ovary syndrome(PCOS) is characterized by clinical symptoms such as menstrual dysfunction, unovulatory infertility, masculinization, obesity, polycystic ovary by ultrasound, and endocrine abnormalities such as hyperandrogenism, and elevated LH to FSH ratio. Recent reports suggest that insulin resistance plays an important role in the pathogenesis of PCOS, and several insulin sensitizing agents have been used for the treatment of PCOS. Troglitazone, one of the thiazolidinediones, improves not only insulin sensitivity but also hyperandrogenism and ovulatory function. Troglitazone appears to be useful in treating women with PCOS. Further investigations are needed to assess the effectiveness and safety.
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PMID:[Troglitazone for treatment of polycystic ovary syndrome]. 1070 78

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. It has become increasingly evident that insulin resistance plays a significant role both as a cause and result of the syndrome. The purpose of this review is to summarize the possible mechanisms leading to insulin resistance and resultant hyperinsulinism (HI) and their interaction with hyperandrogenism (HA) in PCOS. We conducted a computerized search of MEDLINE for relevant studies in the English literature published between January 1966 and January 2000. We reviewed all studies that investigated the roles of insulin, insulin receptor, and insulin gene in insulin resistance and its interaction with hyperandrogenism in PCOS. Insulin resistance in PCOS seems to involve a postbinding defect in the insulin receptor and/or in the receptor signal transduction. Current research has focused on identifying a genetic predisposition for insulin resistance in this syndrome. The answer to the question whether HI or HA is the initiating event is still unclear inasmuch as there are clinical and molecular evidences to support both of these approaches. Our view is that whichever is the triggering insult, a vicious cycle is established where HI acts to aggravate HA and vice versa. In this model, obesity and genetic predisposition seem to be the independent factors that can give rise or contribute to HI, HA, or both simultaneously. It seems that "hyperinsulinemic hyperandrogenism" represents a significant subgroup of PCOS, which probably needs to be renamed and reclassified in the light of this new approach.
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PMID:Hyperinsulinism and its interaction with hyperandrogenism in polycystic ovary syndrome. 1080 39

Recent diagnostic and pharmacologic developments have focused renewed attention on polycystic ovary syndrome. Clinical features of the syndrome include anovulation, hyperandrogenism and menstrual dysfunction, but several other abnormalities, including hyperinsulinemia, luteinizing hormone hypersecretion, elevated testosterone levels and acyclic estrogen production, have been documented. Accompanying obesity and lipid abnormalities compound the risk of developing diabetes mellitus or cardiovascular disease, and chronic anovulation increases the risk for endometrial cancer. A careful history and physical examination should guide diagnostic testing. Slowly progressive hyperandrogenic symptoms with anovulation of peripubertal onset often represent polycystic ovary syndrome. Treatment goals include symptom management and the identification and prevention of potential cardiovascular risks. Treatment should take into account the patient's desire for fertility. Advances in transvaginal ultrasonography and infertility treatments, including newer medications, have facilitated assisted reproduction in patients with polycystic ovary syndrome. Ongoing pharmacologic research focusing on the treatment of insulin resistance appears promising in reversing the longterm complications of the syndrome.
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PMID:Polycystic ovary syndrome: it's not just infertility. 1099 32

Medical management of congenital adrenal hyperplasia (CAH) patients has led to suboptimal results in most cases. High glucocorticoid doses, often needed to suppress adrenal androgen production, may lead to signs of Cushing syndrome. Incompletely suppressed androgen levels commonly lead to premature closure of growth centers, acne, virilization, precocious puberty, irregular or absent menses, and decreased fertility in female CAH patients. A newly proposed therapy for CAH patients is bilateral adrenalectomy. Three Caucasian female patients with 21-hydroxylase deficiency were treated with bilateral adrenalectomy. Two of the three procedures were accomplished laparoscopically. In each patient, medical management alone was unsuccessful. Two patients had salt-losing 21-hydroxylase deficiency. The third patient had uncontrolled hyperandrogenism complicated by obesity and glucose intolerance. All patients had low height percentiles with respect to their normalized percentiles for weight. Bone age was advanced in one patient. Androgen and renin levels were well controlled in two patients, whereas the third patient had persistent hyperandrogenism. Bilateral adrenalectomy was performed at the ages of 14, 19, and 30 years with follow-up, to date, of 25 months, 10 months, and 26 months, respectively. Postoperatively, all patients were free from hyperandrogenism. One patient experienced one episode of urosepsis precipitating an addisonian crisis. Bilateral adrenalectomy may successfully address the problems of increasing steroid requirements and hyperandrogenism in patients with severe CAH. The ability to perform this operation laparoscopically coupled with the overall metabolic benefits make bilateral adrenalectomy a reasonable alternative to lifelong androgen suppression in select patients.
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PMID:Study of three patients with congenital adrenal hyperplasia treated by bilateral adrenalectomy. 1103 5

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. An adverse lipid profile has also been observed in PCOS-affected women, suggesting that these individuals may be at increased risk for coronary heart disease at a young age. The objective of the present study was to evaluate subclinical atherosclerosis among women with PCOS and age-matched control subjects. A total of 125 white PCOS cases and 142 controls, aged >/=30 years were recruited. Collection of baseline sociodemographic data, reproductive hormone levels, and cardiovascular risk factors was conducted from 1992 to 1994. During follow-up (1996 to 1999), these women underwent B-mode ultrasonography of the carotid arteries for the evaluation of carotid intima-media wall thickness (IMT) and the prevalence of plaque. A significant difference was observed in the distribution of carotid plaque among PCOS cases compared with controls: 7.2% (9 of 125) of PCOS cases had a plaque index of >/=3 compared with 0.7% (1 of 142) of similarly aged controls (P=0.05). Overall and in the group aged 30 to 44 years, no difference was noted in mean carotid IMT between PCOS cases and controls. Among women aged >/=45 years, PCOS cases had significantly greater mean IMT than did control women (0.78+/-0.03 versus 0.70+/-0.01 mm, P:=0. 005). This difference remained significant after adjustment for age and BMI (P:<0.05). These results suggest that (1) lifelong exposure to an adverse cardiovascular risk profile in women with PCOS may lead to premature atherosclerosis, and (2) the PCOS-IMT association is explained in part by weight and fat distribution and associated risk factors. There may be an independent effect of PCOS unexplained by the above variables that is related to the hormonal dysregulation of this condition.
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PMID:Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. 1107 46


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