Insulin resistance,polycystic ovary syndrome,and type 2 diabetes mellitus

Objective: To review the definition and prevalence of two insulin resistance (IR)-associated phenotypes, polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus, as well as the risk and nature of their simultaneous presentation.

Design: Review of published literature.

Result(s): Insulin resistance affects between 10% and 25% of the general population. Two common disorders frequently associated with IR are PCOS, affecting 4% to 6% of reproductive-aged women, and type 2 diabetes mellitus, which is observed in about 2% to 6% of similarly aged women. Overall, about 50% to 70% of women with PCOS and 80% to 100% of patients with type 2 diabetes mellitus have variable degrees of IR. Insulin resistance and its secondary hyperinsulinemia appear to underlie many of the endocrine features of PCOS in a large proportion of such patients. The risk of type 2 diabetes mellitus among PCOS patients is 5- to 10-fold higher than normal. In turn, the risk of PCOS among reproductive-aged type 2 diabetes mellitus patients appears to be similarly increased.

Conclusion(s): It remains to be determined whether PCOS and type 2 diabetes mellitus represent no more than different clinical manifestations of the same IR syndrome, with their phenotypic differences due to the presence or absence of a coincidental genetic defect at the level of the ovary or pancreas, respectively, or representing the result of etiologically different subtypes of IR syndromes.     

Polycystic ovary syndrome

The polycystic ovary syndrome (PCOS) is the most frequent endocrine disease in women of reproductive age. Hyperandrogenism, anovulation and metabolic syndrome are the cardinal features of PCOS. Hyperandrogenism results from a diffuse enzymatic hyperactivity at the theca-interstitial cell level. Anovulation is due to an impairment of the selection of a dominant follicle, while the number of smaller follicles is exaggerated. The molecular grounds of insulin resistance could be an increased Serine phosphorylation of the insulin receptor. The clinical classification of PCOS distinguishes three forms: the classic PCOS, where the three above mentioned features are present, the non classic PCOS and the asymptomatic PCOS, revealed by ultrasonography. Only the increased ovarian volume or surface (>11ml and> 5.5cm(2), respectively) must be viewed as a specific ultrasonic sign of PCOS. Cyproterone acetate remains the basic treatment of hyperandrogenism. The treatment of anovulation and infertility follows a consensual strategy. The insulin sensitizing treatment allows to decrease hyperandrogenism, to reverse the menstrual cycle irregularity and to obtain spontaneous or induced pregnancies.     

Polycystic ovary syndrome

Women with polycystic ovarian syndrome have chronic anovulation and androgen excess not attributable to another cause. This condition occurs in approximately 4% of women. The fundamental pathophysiologic defect is unknown, but important characteristics include insulin resistance, hyperandrogenism, and altered gonadotropin dynamics. Inadequate follicle-stimulating hormone is hypothesized to be a proximate cause of anovulation. Obesity frequently complicates polycystic ovarian syndrome but is not a defining characteristic. The diagnostic approach should be based largely on history and physical examination, thus avoiding numerous laboratory tests that don't contribute to clinical management. Women with polycystic ovarian syndrome typically present because of irregular bleeding, hirsutism, and/or infertility. These conditions can be treated directly with oral contraceptives, oral contraceptives plus spironolactone, and ovulation induction, respectively. However, women with polycystic ovarian syndrome also have a substantially higher prevalence of diabetes and increased risk factors for cardiovascular disease. They should also be screened, therefore, for these conditions and followed closely if any risk factors are uncovered. For obese women with polycystic ovarian syndrome, behavioral weight management is a central component of the overall treatment strategy.     

Polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy, affecting 5-10% of the female population. It involves overproduction of ovarian androgens leading to a heterogeneous range of symptoms including hirsutism, acne, anovulation and infertility. Hyperinsulinaemia, exacerbated by obesity, is often a key feature. Treatment depends on the presenting symptoms, which may often be ameliorated by weight loss where relevant. Anti-androgen preparations are used for hyperandrogenic symptoms, and clomiphene citrate (CC) is the first-line treatment for anovulation and infertility. Aromatase inhibitors are being investigated as an alternative to CC. Failure to conceive with CC can be treated in a number of ways, including the addition of insulin-lowering agents (mainly metformin), low-dose gonadotrophin therapy or surgically by laparoscopic ovarian drilling. Although the exact aetiology of PCOS is not known, the therapeutic alternatives provide reasonably successful symptomatic treatment.     

Polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting between 4% and 8% of reproductive aged women. This syndrome, a complex disorder with multiple components, including reproductive, metabolic, and cardiovascular manifestations, has long-term health concerns that cross the life span. The diagnostic criteria for PCOS are ovarian dysfunction evidenced by oligomenorrhea or amenorrhea and clinical evidence of androgen excess (e.g., hirsutism and acne) in the absence of other conditions that can cause these same symptoms. This article reviews current knowledge about the pathophysiology, clinical manifestations, diagnosis, and management of this disorder.     

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Polycystic ovary syndrome and bulimia

One hundred fifty-three patients classified as suffering from polycystic ovarian syndrome (PCOS) and 109 patients who were suffering from a clear organic disorder or endocrinopathy received the bulimia investigation test (Edinburgh) (BITE) questionnaire for abnormal eating behaviors. Patients with PCOS showed a significant increase in their mean BITE score for approximately a third had abnormal eating patterns, and 6% have scores suggestive of clinical bulimia compared with only 1% of women in the group with organic endocrinopathies. The work suggests that women with PCOS should be screened for abnormal eating behaviors and raises the possibility that treatment by psychological means should be considered when abnormal eating behaviors are present.     

Polycystic ovary syndrome and hyperprolactinemia

Analysis of the evidence linking PCOS and hyperprolactinemia suggests that these conditions have independent origins. Elevated prolactin serum levels are documented in the early studies of patients with polycystic ovaries. However, recent investigators using serial serum sampling have excluded transient elevations of prolactin and have shown a less frequent association of these disorders. Treatment of individuals with both PCOS and hyperprolactinemia is distinct from the management of the individual with only one of these conditions. Upon evaluating the therapeutic alternatives for dysfunctional uterine bleeding and hirsutism in these patients, the effect of exogenous estrogen and progesterone on the secretion of prolactin must be considered. The addition of a dopamine agonist (e.g., bromocriptine or cabergoline) to a regimen of clomiphene citrate must also be considered as ovulation induction options for these women. Finally, future discoveries about the relationship between PCOS and hyperprolactinemia will require a better understanding of how the hypothalamus regulates the pituitary secretion of LH and prolactin.     

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in Asian women with polycystic ovary syndrome.

OBJECTIVES: To determine the prevalence of abnormalities of glucose metabolism in Asian women with polycystic ovary syndrome (PCOS) and to assess the different impacts of the 1985 and 1999 WHO consultations and the ADA criteria for the diagnosis of type 2 diabetes mellitus (DM). METHODS: Eighty-five women with PCOS were consecutively included in the study at the Reproductive Endocrinology Unit, Department of Ob-Gyn, Ramathibodi Hospital, Mahidol University. All women underwent a standard oral glucose tolerance test (OGTT). Fasting insulin and testosterone levels were also measured. RESULTS: Seventy-nine women consented to the OGTT. The prevalence of impaired glucose tolerance (IGT) and type 2 DM was 22.8 and 15.2% with the 1985 WHO criteria, and 20.3 and 17.7% according to the 1999 WHO consultation criteria, respectively. The recommendation of the ADA using the fasting glucose levels could only determine a prevalence of 6.3% for type 2 DM. The fasting insulin and testosterone levels were significantly higher in DM than IGT and normal glucose tolerance (NGT) subgroups. The PCOS women with abnormalities of glucose metabolism had a greater body mass index (BMI), higher fasting glucose and 2-h post-load glucose levels than those with NGT. The prevalence of glucose intolerance significantly increased with BMI. CONCLUSIONS: Similar to other ethnic populations, Asian women with PCOS are at risk of developing IGT and type 2 DM especially if obese. The recommendation of the ADA is not appropriate for the diagnosis of type 2 DM in PCOS women.     

Polycystic ovary syndrome and ovulation induction

Polycystic ovary syndrome (PCOS) is likely the most common cause of anovulatory infertility. Although many options are available for ovulation induction in these patients, there is currently no evidence-based algorithm to guide the initial and subsequent choices of ovulation induction methods. In obese women with PCOS, mild to moderate weight loss results in improvement of ovulatory dysfunction, and should be advocated at the onset of the evaluation. Clomiphene citrate is currently the 1st line medical therapy for ovulation induction. Glucocorticoids do not result in consistent ovulation and have significant side effects. Exogenous pulsatile GnRH treatment has low ovulation and pregnancy rates with a high risk of miscarriage. The most commonly used medical agents for ovulation induction in clomiphene-resistant women with PCOS are parenteral gonadotropins. Various gonadotropin preparations and different protocols are available; however the risk of multiple pregnancy and ovarian hyperstimulation is high with gonadotropin therapy. The frequent association between PCOS and insulin resistance has prompted recent studies on the effect of insulin-sensitizing agents on spontaneous and as an adjuvant to conventional ovulation induction therapies. Overall, the improvement in ovulation with insulin sensitizing drugs is modest, and unresolved issues such as variability in ovarian response remain to be addressed in future studies. Nevertheless, these agents may be beneficial in a subset of PCOS patients. Surgical ovulation induction methods such as ovarian diathermy have been reported to be moderately effective. However, due to the inherent associated risks and unknown effect on long-term reproductive potential, this modality should be reserved for patients who are clomiphene-resistant and unable or unwilling to proceed to gonadotropin therapy.     

Polycystic ovary syndrome and endometrial cancer

An association between polycystic ovary syndrome (PCOS) and endometrial carcinoma was first suggested in 1949. Since then, several studies have been published that appear to support this association, and it is common practice among gynecologists and physicians to prescribe hormonal treatment to reduce this perceived risk, although there is no consensus as to the subgroup of PCOS in whom this is required. The mechanism(s) underlying any association are also unclear, but it is again widely assumed that chronic anovulation, which results in continuous estrogen stimulation of the endometrium unopposed by progesterone, is a major factor. However, obesity, hyperinsulinemia, and hyperandrogenism, which are also features of PCOS, are risk factors for endometrial carcinoma, but it does not necessarily follow that the incidence or mortality from endometrial cancer is increased in women with the syndrome. Potential strategies to prevent endometrial cancer in PCOS women are discussed.     

Polycystic ovary syndrome and ovulation induction

Before initiating treatment to induce ovulation in cases of PCOS, an appropriate evaluation of the patient and her partner, based on individual considerations, is important to optimize outcome. For obese patients with PCOS, weight-loss measures should be pursued before pharmacologic treatment is initiated. For most patients, the pharmacologic agent of choice to induce ovulation is clomiphene citrate, alone or in combination with a glucocorticoid. Treatment with metformin, alone or in combination with clomiphene citrate, may also be beneficial. For patients not responsive to clomiphene citrate, injectable gonadotropin treatment is usually warranted, although, depending on individual circumstances, laparoscopic ovarian drilling may be appropriate.