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POSITION STATEMENT |
Division of Endocrinology and Metabolism, and Departments of Internal Medicine (K.E.S.S., E.P.W., P.A.E., J.E.N.), Pharmacy (K.I.C.), Pediatrics (E.P.W., N.W.K.), and Obstetrics and Gynecology (N.W.K., J.E.N.), Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0111
Address all correspondence and requests for reprints to: John E. Nestler, M.D., Division of Endocrinology and Metabolism, Virginia Commonwealth University, P.O. Box 980111, Richmond, Virginia 23298-0111. E-mail: jnestler{at}mcvh-vcu.edu.
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Abstract |
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 Top Abstract IntroductionProcessDevelopment of IGT and...Current Controversies in...Measurement of Glucose...Prevention and Treatment of...Glucose Intolerance in...Conclusion and RecommendationsMinority ReportFuture DirectionsReferences |
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Participants: The expert panel was appointed by the Androgen Excess Society (AES) to review the literature and make recommendations based on the available evidence. Meetings were open, and there was no funding for the panel.
Evidence: A systematic review was conducted of the published, peer-reviewed medical literature using MEDLINE to identify studies that addressed the prevalence, risk factors, testing, and treatment for IGT in both adults and adolescents with PCOS. Unpublished data were not considered.
Consensus Process: The panel held meetings to review the literature and draft the statement as a committee. The AES board members reviewed and critiqued the manuscript, and changes were made based on their comments.
Conclusions: The panel recommends that all patients with PCOS be screened for IGT with a 2-h oral glucose tolerance test. A few members of the AES board recommend alternatively screening women with PCOS for IGT and type 2 DM using an oral glucose tolerance test only in patients with a body mass index of 30 kg/m2 or greater or in lean patients with additional risk factors. Patients with normal glucose tolerance should be rescreened at least once every 2 yr, or more frequently if additional risk factors are identified. Those with IGT should be screened annually for development of type 2 DM. PCOS patients with IGT should be treated with intensive lifestyle modification and weight loss and considered for treatment with insulin-sensitizing agents.
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Introduction |
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TopAbstractIntroductionProcessDevelopment of IGT and...Current Controversies in...Measurement of Glucose...Prevention and Treatment of...Glucose Intolerance in...Conclusion and RecommendationsMinority ReportFuture DirectionsReferences |
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Given the significant metabolic burden of insulin resistance seen in women with PCOS, affected women may have an increased risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). IGT is a known risk factor for type 2 DM and the development of cardiovascular disease (7). Because IGT is often asymptomatic, the screening of women with PCOS for IGT has been recommended; however, recommendations have varied regarding the timing and method of screening for IGT (8, 9). Because patients with PCOS are at high risk for developing IGT, the early identification of affected patients and institution of lifestyle changes or pharmacological treatments may help delay the progression to type 2 DM. The following consensus recommendations attempt to determine the optimal screening method, timing of screening, and treatment modalities for IGT among women with PCOS based on the currently available medical literature.
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Process |
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To review the natural history of PCOS and IGT, MEDLINE was searched from 1966 through 2007. Medical Subject Headings (MeSH) used included polycystic ovary syndrome (which includes polycystic ovarian disease) or ovarian hyperandrogenism and diabetes, IGT, β-cell dysfunction, gestational diabetes, or metabolic syndrome. Additional references identified from these initial articles were also considered.
To examine risk factors for IGT in PCOS, the MEDLINE MeSH headings used were PCOS or ovarian hyperandrogenism, and glucose intolerance and risk factors, with the following limitations: major topic (PCOS) and English and humans. Cross-referenced studies were also reviewed.
To review the measurements of IGT, MEDLINE was searched using the terms IGT and measure. PCOS or ovarian hyperandrogenism were added in a subsequent search. Furthermore, the MeSH heading glucose intolerance with the subheading diagnosis was searched by itself and combined with the MeSH heading polycystic ovary syndrome. Supplementary references were obtained from initial citations.
To review treatments for IGT, MEDLINE was searched using the terms: type 2 diabetes prevention; PCOS and diabetes prevention; ovarian hyperandrogenism and diabetes prevention; and IGT prevention, and IGT treatment with the limits (clinical trial, metaanalysis, or randomized-controlled trial). During evaluation, particular emphasis was placed on identifying prospective randomized, controlled studies that enrolled at least 100 subjects, included women as part of their study population, involved an intervention and follow-up period of at least 1 yr, and clearly defined the prevalence of glucose intolerance at baseline and the end of the study period.
To examine the development, measurement, and treatment of IGT in adolescents, MEDLINE was searched using the terms PCOS, glucose intolerance, and adolescents, and ovarian hyperandrogenism and glucose intolerance. Insulin resistance was also used as a search term, but only studies that assessed IGT were reviewed.
Unpublished data or data published only in abstract form were not included in the review.
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Development of IGT and Type 2 DM |
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TopAbstractIntroductionProcessDevelopment of IGT and...Current Controversies in...Measurement of Glucose...Prevention and Treatment of...Glucose Intolerance in...Conclusion and RecommendationsMinority ReportFuture DirectionsReferences |
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Prevalence of glucose intolerance in women with PCOS
In two of the largest studies (>100 women) to date that documented the prevalence of IGT and type 2 DM in women with PCOS, it is estimated that IGT is present in 31–35% of women with PCOS (10, 11). In addition, type 2 DM, classified according to the World Health Organization (WHO) criteria, is present in 7.5–10% of women with PCOS. Compared with the prevalence of IGT (1.6%) and DM (2.2%) found in U.S. women of similar age in the Third National Health and Nutrition Survey (12), the rates in women with PCOS are considerably higher. In addition, IGT and type 2 DM are also highly prevalent among adolescents with PCOS. In one study, IGT was present in eight of 27 (29.6%), and type 2 DM was present in two of 27 (7.4%) adolescent girls with PCOS (13).
The majority of U.S. studies evaluating the prevalence of glucose intolerance in PCOS primarily included obese women, which aggravates their risk for glucose intolerance. Studies on the prevalence of glucose intolerance are limited in Europe where women with PCOS are substantially leaner. However, it has been shown that glycemic abnormalities are not restricted to Caucasian women with PCOS. A high prevalence of abnormal glucose tolerance has been documented in Chinese (20.5%) and Thai (20.3%) women with PCOS (14, 15). Current studies also support abnormal glucose homeostasis in Japanese women with PCOS (16, 17), although one study (17) suggests that obesity may have a stronger effect than the existence of PCOS. In Indian populations, women with PCOS appear to have worse glucose tolerance than Caucasian populations (18).
Conversion rates to IGT and type 2 DM
The conversion from IGT to frank diabetes is also substantially enhanced in women with PCOS. In an uncontrolled study, Norman et al. (19) assessed 77 Australian women with PCOS. During an average 6.2-yr follow-up, five of 54 (9.3%) women with normal glucose tolerance (NGT) at baseline developed IGT, and another four women (7.4%) progressed from normoglycemia to type 2 DM. Among the 13 women with IGT at baseline, seven of them (5.4%) developed DM at follow-up. Furthermore, BMI at baseline appeared to be an independent predictor of worsening glycemic control.
The enhanced rate of deterioration in glucose tolerance was corroborated by Legro et al. (20), who assessed the changes in glucose tolerance over time in 71 U.S. women with PCOS and 23 control women who had baseline NGT. The mean follow-up period was approximately 3 yr. In this study, of 35 women with PCOS with NGT at baseline, 17 converted to IGT, equivalent to a NGT to IGT conversion rate of 16% per year. In addition, in this study the conversion rate from IGT to DM among PCOS women was 2% per year. Conversely, seven women with PCOS who had abnormal glucose tolerance at baseline reverted in their WHO glucose tolerance category. The conversion rate from NGT to IGT in the control women is less prominent. Of 23 control women who had NGT at baseline, only five converted to IGT, which is less than half the rate of women with PCOS. There are little data on conversion rates from European countries.
Development of gestational DM (GDM)
Besides converting to IGT or type 2 DM, women with PCOS are also at high risk for developing GDM. Polycystic ovarian morphology is a common finding among women with a history of GDM (21, 22). In a metaanalysis of 720 women with PCOS and 4505 controls, PCOS women have a 2.94 times [confidence interval (CI) for odds ratio 1.70–5.08] higher risk of developing GDM than control women (23). This risk estimate was recently confirmed by a large database study performed using a multiethnic population in the Northern California Kaiser Permanente program (24).
Mechanisms of glucose intolerance in PCOS
Several mechanisms have been postulated to account for the predisposition to the development of type 2 DM among women with PCOS. Dunaif et al. (6, 25) demonstrated that women with PCOS are insulin resistant, independent of obesity. Although the nature of insulin resistance in PCOS is currently unclear, defects in insulin receptor or post-receptor signal transduction (25), altered adipocyte lipolysis (26, 27), decreased glucose transporter 4 in adipocytes (28), and impaired release of a D-chiro-inositol mediator (29, 30, 31) have all been implicated. Furthermore, many women with PCOS exhibit β-cell dysfunction (32, 33, 34, 35), rendering insulin response to a glucose load insufficient for the degree of insulin resistance in PCOS.
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Current Controversies in Screening for Glucose Intolerance |
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).
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In addition to evaluating family history as a risk factor, Legro et al. (11) also showed an increased risk for IGT in women with advanced age, increased BMI, and increased waist to hip ratios, which are identical risk factors for the general population in developing IGT. This was corroborated in a cross-sectional study of 91 women with PCOS by Trolle and Lauszus (37), who found women who were older and had a higher BMI were more likely to have elevated fasting glucose levels. In women with a history of GDM, Koivunen et al. (38) found an increased prevalence of an abnormal OGTT as well as a higher prevalence of PCOS (39.4 vs. 16.7%; P = 0.03) when compared with controls.
There remains some controversy in the practicality of screening all patients with PCOS for IGT. Due to the time-consuming nature of the OGTT, Mohlig et al. (39) investigated the use of decision tree modeling in 118 women with PCOS to determine whether the number of patients with PCOS who should undergo the OGTT could be decreased. The best decision tree used the homeostasis assessment model for estimating insulin resistance, the proinsulin to insulin ratio, proinsulin, 17-OH progesterone, and the ratio of LH to FSH. The sensitivity of this tree was 100% and the specificity was 74%, and it cut down on the number of OGTTs by about 60%. The most suitable decision tree using medical history and clinical parameters only used BMI (>25.7 kg/m2), waist circumference (>76 cm), and waist to hip ratio (>0.77). Applying the clinical data tree alone to a stratified screening algorithm reduced the number of OGTTs in patients with PCOS by about 25%. This decision tree yielded a sensitivity for the detection of IGT of 100%, with a specificity of 32.3%. Thus, the use of this decision tree correctly identified all women with IGT. However, the widespread application of this tree needs to be confirmed by larger studies.
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Measurement of Glucose Intolerance |
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TopAbstractIntroductionProcessDevelopment of IGT and...Current Controversies in...Measurement of Glucose...Prevention and Treatment of...Glucose Intolerance in...Conclusion and RecommendationsMinority ReportFuture DirectionsReferences |
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). The WHO criteria recommend first measuring a fasting plasma glucose level, followed by a 2-h OGTT only in individuals with impaired fasting glucose (IFG), i.e. fasting plasma glucose level between 110 and 125 mg/dl (6.1–6.9 mmol/liter). IGT is then defined as a 2-h fasting glucose equal to or more than 140 mg/dl and less than 199 mg/dl (7.8–11.0 mmol/liter) (40). The ADA also defines IGT as a 2-h plasma glucose of 140–199 mg/dl (7.8–11.0 mmol/liter) but does not require a fasting glucose before the performance of the OGTT (9).
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Several studies have shown that the fasting plasma glucose and the OGTT do not identify the same group of patients (45, 46, 47, 48). The Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe (DECODE) study (45) demonstrated in a group of 1517 individuals with newly diagnosed DM that 40% met the criteria by fasting plasma glucose only, 31% met the criteria by a 2-h OGTT only, and 28% met both criteria. Therefore, nearly one third of individuals with DM would have been missed using fasting plasma glucose only. In a study of 5023 Pima Indians, Gabir et al. (48) reported that IGT was more common than IFG (15 vs. 5%). In fact, IGT, measured by an OGTT, is typically more common in women, whereas IFG, measured by fasting plasma glucose, is more common in men (40). In women with PCOS, Legro et al. (11) revealed that the majority of PCOS women with IGT have normal fasting glucose levels. In the PCOS population studied, fasting plasma glucose measurements by ADA criteria failed to diagnose 58% of women with DM diagnosed by a 2-h OGTT. Therefore, in PCOS, measurement of fasting blood glucose misses even more persons with IGT and DM than in the general population.
IGT is a strong predictor for DM, as well as risk of cardiovascular disease and premature mortality (7, 48, 49, 50, 51). A 7-yr cohort study reported that IGT, but not IFG, is a risk factor for cardiovascular disease (5). In the Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe study (45), hazard ratios (95% CI) for DM diagnosed by a fasting plasma glucose were 1.6 (1.4–1.8) for all-cause mortality, 1.6 (1.3–1.9) for cardiovascular mortality, and 1.6 (1.4–1.9) for noncardiovascular mortality, respectively. The corresponding hazard ratios for DM by a 2-h OGTT were 2.0 (1.7–2.3), 1.9 (1.5–2.4), and 2.1 (1.7–2.5). In terms of prevention, the ADA acknowledges that although the efficacy of interventions for primary prevention of type 2 DM has been well recognized in individuals with IGT, there are presently no data regarding individuals with IFG who do not also have IGT (9). Data are also nonexistent regarding primary prevention of premature mortality and cardiovascular disease in individuals with IFG only (40).
The OGTT is a simple test and can be performed in an office laboratory setting. Based on current evidence and because the majority of women with PCOS have normal fasting plasma glucose, the 2-h OGTT is the best screening measure for glucose intolerance and diagnosis of type 2 DM in women with PCOS.
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Prevention and Treatment of Glucose Intolerance in PCOS |
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Lifestyle modification
The characteristics and results of five studies evaluating the role of lifestyle modification, including dietary modification and regular moderate activity, in preventing the development of type 2 DM among high-risk individuals are outlined in Table 3. Of note, there were significant variations in the reported effects of lifestyle modification on the conversion of IGT to DM among high-risk populations.
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Studies by Pan et al. (54) and Ramachandran et al. (55) also demonstrated a significant but less dramatic relative risk reduction (28–38%) in the conversion rate from IGT to diabetes with intensive lifestyle modification. The discrepancies among the reported differences in risk reduction with lifestyle modification may be partially explained by differences in the study populations. The mean BMI measurements in the studies by Pan et al. (54) and Ramachandran et al. (55) were 25–26 kg/m2, lower than the mean BMI measurements in the DPP and Finnish Diabetes Prevention Study.
A study by Wein et al. (56) involving 200 women with a history of GDM and current IGT demonstrated a small but nonsignificant reduction in the diabetes conversion rate; however, the study intervention included dietary modification alone. Finally, one smaller study by Wing et al. (57) failed to show a significant difference in the development of diabetes with diet alone, exercise alone, or a combined intervention in overweight subjects with a family history of diabetes.
Little is known regarding the role of exercise in preventing the development of IGT and DM in nonobese women with PCOS.
Pharmacological intervention
Pharmacological therapies, including insulin-sensitizing agents, have also been shown to decrease the conversion rate to overt DM among subjects with IGT, and randomized-controlled trials evaluating pharmacotherapy that met the specified criteria are outlined in Table 4. Treatment with medications from a variety of different drug classes, including the biguanide, metformin (52, 55), thiazolidinediones (58, 59), the 
-glucosidase inhibitor, acarbose (60), and the lipoprotein lipase inhibitor, orlistat (61, 62), has prevented the development of DM among high-risk populations with IGT.
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Similar to the DPP, the Indian Diabetes Prevention Program (IDPP) evaluated the role of lifestyle modification and metformin in the prevention of DM among overweight Asian Indian men and women with IGT (55). The IDPP results revealed significant, 28.5 and 26.4%, relative risk reductions for the development of DM with intensive lifestyle modification and metformin treatment, respectively. Although both lifestyle modification and metformin therapy reduced the incidence of DM in the IDPP, there was no added benefit from the combination lifestyle modification and metformin compared with either treatment alone. As outlined previously, the less robust reduction in DM risk reported with lifestyle modification in the IDPP compared with the DPP may be explained by differences in subject BMIs at baseline between the two studies (25.7 ± 3.3 kg/m2 in the IDPP compared with 33.9 ± 6.8 kg/m2 in the DPP).
Similar to metformin, the thiazolidinediones improve insulin sensitivity and may prevent or delay the development of DM in high-risk individuals. Randomized, placebo-controlled trials involving the prevention of DM using thiazolidinediones demonstrated a 62–89% relative risk reduction with this class of medications (58, 59). Unfortunately, these studies did not compare treatment with thiazolidinediones with intensive lifestyle modification or other medications. The DPP initially contained a treatment arm that was randomized to receive the thiazolidinedione, troglitazone; however, given concerns of hepatotoxicity, the troglitazone arm was discontinued in 1998 (64). Before its discontinuation, the incidence of DM among the 585 subjects receiving troglitazone for a mean duration of 0.9 yr was statistically lower than the incidence in both the placebo and metformin groups. Furthermore, there was no statistical difference in the progression rate to DM between the troglitazone and intensive lifestyle modification treatment arms. Despite these findings, longer term studies are needed to compare the efficacy of thiazolidinediones and other insulin-sensitizing agents and lifestyle modification in preventing DM.
Prevention of glucose intolerance in PCOS
Although there are no published prospective, randomized-controlled trials that evaluate the prevention or treatment of IGT specifically in women with PCOS, several small studies do address the potential role of insulin-sensitizing agents in this high-risk population. Unluhizarci et al. (65) reported the impact of treatment with metformin 500 mg twice daily for 3 months on IGT in 17 adult women with PCOS (mean age 24.4 ± 1.4 yr; mean BMI 29.7 ± 1.4 kg/m2). At baseline, five (31.6%) of the women demonstrated IGT. Of these, two patients (40%) showed NGT after treatment with metformin. In a study by Arslanian et al. (66), 15 obese adolescents with PCOS and IGT (mean age 14.0 ± 0.8 yr; mean BMI 38.1 ± 1.6 kg/m2) were treated with metformin 850 mg twice daily for 3 months. At the end of the relatively brief treatment period, approximately one half (n = 8) of the adolescents had reverted back to NGT on repeat testing. In a study by Dereli et al. (67), 40 women with PCOS, a BMI less than 27 kg/m2, and IGT were randomized to treatment with rosiglitazone with either 2 (n = 20) or 4 mg daily (n = 20) for 8 months. In addition to decreases in free testosterone levels and improvements in ovulatory dysfunction in both treatment groups, 19 (95%) and 15 (75%) of the women receiving rosiglitazone 4 and 2 mg daily, respectively, had reverted to NGT after 8-month treatment.
Finally, using a retrospective study design, Sharma and Nestler (68) evaluated the role of metformin in preventing the progression of glucose intolerance in PCOS. At baseline, 11 (22%) of the 50 nondiabetic women with PCOS had evidence of IGT according to an OGTT. After a mean treatment period of 2.4 yr, approximately half (n = 6) the women with IGT at baseline had reverted to NGT with metformin therapy. Furthermore, while receiving metformin (average treatment period of 3.6 yr), only two (5.1%) of the 39 women with NGT at baseline had converted to IGT, representing an annual conversion rate of 1.6%. None of the women with IGT at baseline converted to overt DM during treatment with metformin. When compared with the 16% annual conversion rate from NGT to IGT among drug-naive PCOS women reported by Legro et al. (20), treatment with metformin appeared to lead to an 8-fold decrease in the annual conversion rate. Despite the limitations of these four studies, including small sample size, lack of control groups, and the question of whether glucose intolerance was prevented or merely being masked, their results support the potential role of insulin-sensitizing agents in the prevention of IGT and DM in PCOS. However, well-designed, prospective, randomized-controlled trials are needed to evaluate more fully the specific roles of lifestyle modification and insulin-sensitizing agents in the prevention of IGT and its progression to type 2 DM among women with PCOS.
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Glucose Intolerance in Adolescents with PCOS |
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Data on glucose intolerance in adolescents with PCOS are limited, and studies are difficult to interpret with confidence, given the small numbers of participants in each study. As in adult women, adolescents with PCOS are at increased risk for developing glucose intolerance and DM compared with their non-PCOS counterparts (11); however, the exact prevalence of IGT in young women with PCOS is less clear. For example, a Canadian study of 22 obese adolescents with PCOS revealed baseline IGT in only one participant (4.5%) (70). In contrast, small studies involving obese adolescents with PCOS in the United States report rates of IGT as high as 33 (13) to 52% (35). These differences may be accounted for by many factors, including, but not limited to, family history, diet, BMI, and exercise habits. Even less is known regarding the risk of IGT in nonobese adolescents with evidence of PCOS or ovarian hyperandrogenism. In two small studies involving a total of 39 nonobese adolescent girls with PCOS by Ibanez et al. (71) and Silfen et al. (72), none of the nonobese adolescents demonstrated IGT on the OGTT.
Measurements of glucose intolerance in adolescents
As in adults, screening for IGT with a fasting glucose level is not reliable in adolescents, and tests of insulin resistance such as the fasting glucose to insulin ratio and the homeostasis assessment model for estimating insulin resistance are poor predictors of IGT and DM in adolescents with PCOS (13). Therefore, the most reliable screening test for IGT in PCOS adolescents is the 2-h OGTT after a 75-g glucose load, interpreted using ADA guidelines. Although the most appropriate screening interval is not clearly defined, the conversion from NGT to type 2 DM can occur in as little as 5 yr (73), most likely because of the strong correlation of PCOS and insulin resistance.
Treatment of IGT in adolescents
Although the literature regarding treatment of IGT specific to adolescents is sparse, it seems reasonable to use a similar approach to that used in adult women with PCOS. Diet and exercise appear to be the most important aspects of treating IGT and reducing progression to type 2 DM. As demonstrated in the DPP (52), lifestyle intervention comprised of a low-fat diet and 150-min exercise per week reduced the progression from IGT to type 2 DM by 58% compared with placebo and was more successful than metformin therapy, which reduced progression by 31%.
A small randomized-controlled trial comparing metformin to placebo for 12 wk in 22 adolescents with PCOS showed no significant difference in IGT (70). Of note, however, the only subject with baseline IGT was in the metformin group and showed persistence of her IGT at the study end. There were no subjects in the placebo arm with baseline IGT, but one developed IGT by the end of the 12-wk study. Clearly, this study was underpowered, and the duration was not sufficient to detect a true difference. Conversely, the only study evaluating PCOS adolescents with baseline IGT showed that treatment with metformin (850 mg twice daily) resulted in conversion back to NGT in eight of the 15 subjects after 3-month treatment (66). Limitations of this study include small sample size and lack of a control group; nonetheless, metformin may be a promising treatment for PCOS adolescents with IGT.
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Conclusion and Recommendations |
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TopAbstractIntroductionProcessDevelopment of IGT and...Current Controversies in...Measurement of Glucose...Prevention and Treatment of...Glucose Intolerance in...Conclusion and RecommendationsMinority ReportFuture DirectionsReferences |
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). Because of the high prevalence of glucose intolerance among patients with PCOS, screening is a necessary part of the care of these patients who are at a markedly increased risk for the development of type 2 DM. Because an increased prevalence of both glucose intolerance and type 2 DM has been found in various ethnic populations, screening should be done regardless of ethnicity. Although numerous risk factors such as obesity and age increase the risk of glucose intolerance, women with PCOS of all ages and weights appear to be at greater risk for glucose intolerance than normal controls. Consequently, the panel recommends that all women with PCOS be screened, even in the absence of additional risk factors and regardless of BMI.
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Acknowledging the presence of limited data, studies suggest a high (16–19%) annual conversion rate from NGT to IGT in PCOS, and the panel recommends screening PCOS women with NGT at baseline and at least once every 2 yr or earlier if additional risk factors are identified. However, given the high risk of progression to overt diabetes, women with PCOS who have IGT should be screened annually using an OGTT.
Intensive lifestyle modification should be considered the mainstay of treatment in all women with PCOS who have IGT to prevent progression to DM. Despite insufficient data in lean women, it is reasonable to recommend that, in all women with PCOS, a lifestyle modification program should consist of at least 30-min moderate activity 5 d/wk. Furthermore, in overweight and obese women with PCOS, a hypocaloric diet is recommended to achieve a minimum of 5–7% weight loss. However, many overweight and obese women with PCOS find significant weight loss difficult to achieve and maintain, and weight loss is not an option for lean women with PCOS. Consequently, the addition of insulin-sensitizing agents such as metformin and thiazolidinediones should be considered in women with PCOS and documented IGT if weight loss attempts fail or are not possible.
Adolescents with PCOS, like their adult counterparts, should be screened for IGT using an OGTT at least once every 2 yr after a normal screen and more frequently after an abnormal screen. Adolescents should also be treated with intensive lifestyle modification, including diet and moderate exercise as initial therapy. The use of metformin or other insulin-sensitizing agents to treat or prevent progression to IGT may be considered but should not be mandated until there have been well-designed, randomized-controlled trials demonstrating their efficacy.
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Minority Report |
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Future Directions |
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TopAbstractIntroductionProcessDevelopment of IGT and...Current Controversies in...Measurement of Glucose...Prevention and Treatment of...Glucose Intolerance in...Conclusion and RecommendationsMinority ReportFuture DirectionsReferences |
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Acknowledgments |
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Footnotes |
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Abbreviations: ADA, American Diabetes Association; AES, Androgen Excess Society; BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; DPP, Diabetes Prevention Program; GDM, gestational diabetes mellitus; IDPP, Indian Diabetes Prevention Program; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; MeSH, Medical Subject Headings; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; PCOS, polycystic ovarian syndrome; WHO, World Health Organization.
Received July 11, 2007.
Accepted September 27, 2007.
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References |
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