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Query: UMLS:C0003128 (anovulation)
 1,718 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance, defined as a diminished effect of a given dose of insulin on glucose homeostasis, is a highly prevalent feature of women with PCOS. Insulin resistance in PCOS is closely associated with an increase in truncal-abdominal fat mass, elevated free fatty acid levels, increased androgens, particularly free testosterone through reduced SHBG levels, and anovulation. The causes for insulin resistance in PCOS are still unknown. One line of evidence suggests that an increase in truncal-abdominal fat mass and subsequently increased free fatty acid levels induce insulin resistance in women with PCOS. Increased effects of corticosteroids and a relative reduction in oestrogen and progesterone seem to be involved in the aberrant body fat distribution. Conversely, there are also results supporting primary, genetic target cell defects as a cause of insulin resistance in PCOS. An explanation for these seemingly contradictory results could be that the group of women with PCOS is heterogeneous with respect to the primary event in carbohydrate/insulin disturbances. Also insulin secretion in PCOS is characterized by heterogeneity. At one end of the spectrum is a large subgroup of mainly obese women with reduced insulin secretion, which appears to result from failure of the beta cells to compensate for insulin resistance in susceptible women, resulting in glucose intolerance and NIDDM. In the insulin-resistant patients with normal glucose tolerance, most of the hyperinsulinaemia is probably due to secondarily increased insulin secretion and decreased insulin degradation. However, a component of the increased first-phase insulin release is not due to measurable insulin resistance. Notably, this is also found in lean women with normal insulin sensitivity, and is not reversed after weight reduction, in contrast to the findings for insulin resistance. The implications of this enhanced insulin release are not fully clear, but it may tentatively be associated with carbohydrate craving and subsequently increased risks for development of obesity and insulin resistance. It may represent a primary disturbance of insulin secretion in PCOS or may be associated with the perturbed steroid balance in anovulation. The insulin-androgen connection in PCOS appears to be amplified by several different mechanisms, notably in both directions, the initiating event probably varying between individuals. Thus insulin increases the biological availability of potent steroids, primarily testosterone, through the suppression of SHBG synthesis. Insulin is also involved as a progonadotrophin in ovarian steroidogenesis, with the possible net result of interfering with ovulation and/or increasing ovarian androgen production in states of hyperinsulinaemia. Conversely, testosterone may indirectly contribute to insulin resistance through facilitating free fatty acid release from abdominal fat, but perhaps also through direct muscular effects at higher serum levels. It seems likely that this constitution, presumably genetic, would provide evolutionary advantages in times of limited nutrition, given the energy-saving effects of insulin resistance. Hypothetically, hyperinsulinaemia (primary) could provide a stimulus to ensure intake of nourishment, but unlimited food supplies could in some cases initiate a vicious 'anabolic' circle, in which several of the proposed amplifying mechanisms between insulin and androgens--in both directions--could take part.
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PMID:Disturbances in insulin secretion and sensitivity in women with the polycystic ovary syndrome. 877 46

Almost two decades of research have greatly increased our knowledge in the complex field of metabolic aberrations in polycystic ovary syndrome, but still many problems remain unsolved. The statistical association between insulin levels and androgens originally put the focus on possible direct cause-and-effect relationships between these factors. Indeed there is evidence that insulin may affect ovarian functions in multiple ways, presumably in some cases causing anovulation and hyperandrogenism. Clearly, insulin may increase biologically active testosterone through reducing SHBG levels. Conversely, major increases in androgen levels may induce muscular changes leading to reduced insulin-mediated glucose uptake. There are suggestions of increased steroidogenesis in both ovarian and adrenal pathways, with the net result of increased androgen production. There are also findings supporting increased corticosteroid production, which could contribute to insulin resistance directly or through promoting accumulation of abdominal fat, a typical feature of over-weight women with PCOS. Free fatty acids, released in great amounts from abdominal fat, may induce insulin resistance. Insulin resistance may also be due to a primary aberration in the insulin receptor. Putatively increased serine phosphorylation may cause both impairment of the insulin signal and increased 17,20 lyase activity, thus suggesting a common cause for insulin resistance and increased androgen production. There are also findings supporting a high prevalence of beta-cell dysfunction in PCOS, ranging from increased insulin secretion, not explained by insulin resistance or BMI, to failing beta-cell function, mainly in obese women during progress to glucose intolerance and NIDDM. Recent genetic findings also support a multifactorial genesis to PCOS, notably with positive findings both in genes regulating steroidogenesis and insulin secretion. It is suggested that PCOS is the result of "thrifty" genes, providing advantages in times of shortage of nutrition such as muscular strength, moderate abdominal fatness and decreased insulin sensitivity, i.e. an anabolic, energy saving constitution. However, when this constitution is exposed to unlimited food supplies and modern sedentary life style a full-blown PCOS with insulin resistance and infertility is triggered, presumably via several mechanisms, which follow a logical amplification system between two basic anabolic hormones, insulin and testosterone.
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PMID:Polycystic ovary syndrome and insulin resistance: thrifty genes struggling with over-feeding and sedentary life style? 985 13

Polycystic ovary syndrome is a complex endocrine disorder of hypothalamic-pituitary dysfunction that presents with anovulation, hirsutism and infertility. Women with PCOS have increased risk for developing NIDDM, dyslipidemia and premature cardiovascular disease. Because of its vague presentation and potential for numerous complications, PCOS should be evaluated carefully. Unfortunately, there is no cure for PCOS, and the treatment has numerous limitations. Weight loss in an obese patient may greatly improve the patient's response to treatment and should be encouraged.
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PMID:Polycystic ovary syndrome. 1103 90