ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Insulin resistance and associated hyperinsulinemia are common features of polycystic ovary syndrome (PCOS). There is evidence that hyperinsulinemia, in susceptible individuals, may play a major pathogenetic role by increasing free androgen levels. However, it remains unclear whether these alterations are primary or secondary defects. Increased exposure to androgens may contribute to impairing insulin action, generating vicious cycles in which it is difficult to recognize the initial defect. Moreover, distinct genetic and environmental mechanisms may be responsible for insulin resistance in different individuals. These women show several risk factors of cardiovascular disease, typically associated with insulin resistance. Recent data support the hypothesis of increased cardiovascular risk in these women, but there is still no definite proof of this. Large prospective studies should assess whether cardiovascular risk actually increases in these women, focusing on the specific role of insulin resistance and associated features in this phenomenon.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Women with PCOS have multiple risk factors for diabetes including obesity, a family history of type 2 diabetes, and abnormalities in insulin action. These may be increased in certain minority groups. There may be independent and additive effects from the presence of hyperandrogenemia, chronic anovulation, and polycystic ovaries. Studies of glucose tolerance in both urban and rural populations have shown rates of glucose intolerance in the range of 30 to 40% in reproductive-aged females with PCOS (both adolescents and adult females). There is poor correlation with fasting glucose levels. These findings justify vigilant screening for these abnormalities with an oral glucose tolerance test (OGTT) and appropriate interventions in a PCOS population. These findings may have substantial clinical relevance because they strongly suggest that women show reproductive abnormalities of androgen excess and irregular menses form a high-risk pool of women for glucose intolerance. Retrospective and preliminary natural history studies suggest that glucose tolerance worsens with age, and therefore periodic repeat OGTT testing is indicated.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The polycystic ovary syndrome (PCOS) is a heterogeneous clinical entity defined as the association of hyperandrogenism with chronic anovulation in women without specific underlying disorders of the adrenal and pituitary glands. On the other hand, all features of the metabolic syndrome, particularly insulin resistance and associated hyperinsulinemia, are present in most women with PCOS. Insulin is a physiologic hormone regulating ovarian functions, specifically ovarian steroidogenesis. Hyperinsulinemia may therefore play a pivotal role in favoring the hyperandrogenic state and related clinical and metabolic alterations. In addition, as originally described by Stein and Leventhal (1), obesity is very common in women with PCOS, particularly the abdominal phenotype. There is consistent evidence that obese women with PCOS may be characterized by a different hormonal environment from that observed in their normal-weight counterparts. The main differences include more severe insulin resistance and hyperinsulinemia and a worsened hyperandrogenic state. Menstrual cyclicity and fertility rate are negatively affected by the presence of insulin resistance and hyperinsulinemia and may be further worsened in obese women with PCOS. Weight loss should represent the first-line approach in the treatment of these patients, because it significantly improves hormonal and metabolic abnormalities and may favor spontaneous ovulation and improve fertility rate in most of them. Individualized pharmacologic support aimed at favoring weight loss and maintenance and improving insulin resistance may play a complementary role in lifestyle interventional programs including dietary modifications and appropriate physical activity. Because of its proven effectiveness, this approach should therefore be widely extended in clinical practice. This, in fact, may ultimately be beneficial even in the prevention of diabetes type 2 and cardiovascular diseases, toward which women with PCOS appear to be susceptible.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The polycystic ovary syndrome (PCOS) is one of the most common human endocrine abnormalities, affecting 4% to 6% of reproductive-aged women. Although patients with PCOS primarily demonstrate excess production of ovarian androgens, elevated adrenal androgen (AA) levels, primarily dehydroepiandrosterone sulfate (DHEAS), are observed in 20 to 30% of patients if age-related normative values are used. Adrenal androgens may contribute to the phenotype of PCOS, including the development of hirsutism. Overall the cause(s) of the excess AAs levels in PCOS remains unclear. Adrenal androgen levels in PCOS appear to be determined, at least in part, by extra-adrenal factors such as ovarian steroids and insulin. Nonetheless, the primary effect of extra-adrenal androgens and insulin appears to be increased sulfotransferase activity, augmenting the conversion of DHEA to DHEAS. In fact most studies have demonstrated a limited role for extra-adrenal factors in the regulation of circulating AA levelsin vivo.Primarily, AAs and AA excess in PCOS (and in normal subjects) appear to be under significant genetic control. Hence, it is possible that AA excess in PCOS may reflect an inherited abnormality of steroidogenesis. However, and consistent with the significant degree of populational heterogeneity observe in AA levels and secretion, it is more probable that the elevated AA levels found in patients with PCOS may actually reflect selection bias, with a disproportionate number of the women with the highest levels of AAs also having the greatest prevalence of PCOS. In essence, elevated AA secretion in women may reflect an exaggerated AA secretion in response to adrenocorticotrophic hormone (ACTH) stimulation, and may be a predisposing risk factor for the development of PCOS.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Whereas alterations in gonadotropin secretion have long been recognized in women with the polycystic ovary syndrome (PCOS), neither the mechanisms subserving these abnormalities nor the full ramifications of such altered secretion are completely understood. Within the past year several studies have examined fundamental aspects of gonadotropin secretion in PCOS, and the relation of such secretion to other hormonal systems. Increased serum LH concentrations in women with PCOS have again been shown to reflect both an increase in the number and amplitude of individual LH pulses and enhanced LH interpulse (basal) secretion. Perhaps paradoxically, short-term fasting in women with PCOS results in increased rather than decreased LH secretion. Whereas there is a strong positive relation between LH and inhibin B in women with PCOS, obesity negatively correlates with inhibin B in both normal and women with PCOS. Thus, the concentration of serum inhibin B in women with PCOS represents a balance between the positive and negative effects of LH and obesity, respectively. The LH secretory process itself in women with PCOS is disorderly, presumably reflecting abnormal regulation. Secretion of target hormones (eg,androstenedione) is also less orderly in women with PCOS. Moreover, the coupling of several hormone systems including LH–testosterone, LH–androstenedione and LH–leptin is disturbed in women with PCOS. The latter is consistent with the premise that both the feedforward (eg,LH stimulating testosterone secretion) and the feedback (eg,testosterone modulating the GnRH-LH secretory system) are deranged in PCOS.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Polycystic ovary syndrome (PCOS) is a common endocrinopathy and cause of anovulation, with abnormally elevated circulating androgens and insulin levels being common components of PCOS. The potential effects of the metabolic and endocrinologic changes seen in PCOS on the human endometrium are likely to be complex and comprise an important area of research.Androgen receptors and steroid receptor co-activators are overexpressed in the endometrium of women with PCOS. In addition, molecular markers of endometrial receptivity including &agr;v&bgr;3integrin and glycodelin are decreased in endometrial biopsy specimens from patients with PCOS. Clinically, reproductive performance of women with PCOS is improved by insulin-lowering agents such as metformin, primarily by restoring ovulation; however, the effects of insulin-lowering agents on endometrium are unknown.In vitrostudies on the effects of insulin on endometrial stromal cells demonstrate that insulin inhibits the normal process of decidualization. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important in the maternal–fetal interface and in the circulation. Hyperinsulinemia results in decreased circulating IGFBP-1 and increased free IGF-1. Thus, a combination of elevated unopposed estrogen, hyperinsulinemia, elevated free IGF-1, elevated androgens, and obesity likely contribute to the endometrial dysfunction, infertility, increased miscarriage rate and endometrial hyperplasia seen in PCOS.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The cellular mechanisms underlying excess ovarian androgen production in patients with polycystic ovary syndrome (PCOS) are presently unknown. Examination of the steroid biosynthesis by theca interna cells isolated from ovaries of normal women and ovaries from women with PCOS has recently advanced our understanding of the steroidogenic abnormalities that result in increased androgen biosynthesis in PCOS. In the past few years, the combined data derived from studies utilizing freshly isolated and propagated theca cells have established that both progestin and androgen biosynthesis are increased in theca cells obtained from PCOS ovaries. This increase in steroid biosynthesis results from selectively increased cholesterol side-chain cleavage (CYP11A), 3&bgr;-hydroxysteroid dehydrogenase type II (HSD3B2) and 17&agr;-hydroxylase (CYP17) gene expression. The finding that increased androgen biosynthesis is a stable characteristic of propagated PCOS theca cells maintained in long-term culture has provided new opportunities to examine the molecular and cellular basis for increased ovarian androgen biosynthesis in patients with PCOS. By characterizing the regulatory systems mediating both metabolic and steroidogenic processes in normal and PCOS theca cells, it is anticipated that new information will be obtained that will provide insight into the relations between insulin resistance, hyperinsulinemia, and hyperandrogenemia in patients with PCOS.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The genetic analysis of polycystic ovary syndrome (PCOS) presents the typical problems associated with the inheritance of a common, complex disorder. Despite evidence for substantial familial aggregation of PCOS the mode of inheritance is uncertain, and no specific contributing genes have been confidently identified. However, materials and methods for testing candidate genes have recently been greatly enhanced by progress in the Human Genome Project. As a result, several genes and chromosomal regions that hold promise have emerged in recent studies of the genetics of PCOS. The authors review results for several candidate genes in detail and provide a catalogue of references and results for many other candidate genes and regions.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Over the past decade, scans to measure bone mineral density have assumed an essential role in the diagnosis of osteoporosis. Although dual X-ray absorptiometry (DXA) scanning of the central skeleton remains the most widely used investigation, a variety of different types of equipment for measuring peripheral sites are now available. However, the poor correlation between different types of measurement and a lack of consensus on how results from peripheral sites should be interpreted have proved a barrier to the more widespread use of these devices. These issues prompt the following questions:which type of measurement best identifies the patients most at risk of fracture?Can the WHO definition of osteoporosis be extended to include peripheral measurements?Does it matter if different patients are selected for treatment using different techniques?Do patients identified using peripheral measurements benefit from treatment to the same degree as those identified using central DXA?Can peripheral measurements be used to monitor response to treatment?These questions are discussed in turn.

ISSN:1068-3097    

出版商:OVID    

年代:2002

数据来源: OVID