Assessing cardiovascular risk in Mediterranean women with polycystic ovary syndrome.

BACKGROUND: Although dyslipidemia is common in the polycystic ovary syndrome (PCOS), current diagnostic guidelines suggest to evaluate only plasma HDL-cholesterol and triglyceride concentrations, assuming that, in this disorder, cardiovascular risk is mainly due to the presence of the metabolic syndrome (MS). In the US, MS has been found in up to 50% of PCOS, but in other countries its prevalence is lower. METHODS: We compared the prevalence of MS with that of increased LDL- and non-HDL-cholesterol levels in 350 Mediterranean PCOS women (244 anovulatory and 106 ovulatory), and 95 normo-weight and 90 body mass index (BMI)- matched controls. RESULTS: The prevalence of MS was 7.1% in PCOS, higher than normoweight and BMI-matched controls (2.4% and 3.5%, respectively, p < 0.05 for both). The prevalence of elevated LDL- and non-HDL-cholesterol levels in PCOS was respectively, 14.9% and 8.6%, higher than normoweight (2.1% and 1.0%, respectively, p < 0.01 for both) and BMI-matched controls (4.4% and 2.2%, respectively, p<0.05 for both). In PCOS, increased LDL-cholesterol was twice more prevalent than MS or non-HDL-cholesterol. Only a minority of PCOS with MS had increased LDL-cholesterol while increased non-HDL-cholesterol was generally associated to increased LDL-cholesterol. CONCLUSIONS: We have found that in Mediterranean PCOS the prevalence of MS is relatively low while elevated LDL-cholesterol levels are more prevalent. Therefore, beyond MS, a more comprehensive lipid evaluation, including LDL-cholesterol, is needed for a more effective assessment of cardiovascular risk in PCOS.

Correlates of increased lean muscle mass in women with polycystic ovary syndrome.

OBJECTIVE: Muscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome (PCOS). In addition, whether lean mass influences carotid intima-media thickness (IMT) in PCOS has not been assessed. DESIGN: Prospective investigation. METHODS: Ninety-five women with PCOS were age- and weight-matched to 90 ovulatory controls. All women had dual X-ray absorptiometry for lean, fat and bone mass, and bone mass density (BMD). Serum testosterone, sex hormone-binding globulin, insulin, and glucose and carotid IMT were determined. Free androgen index (FAI) and insulin resistance (by QUICKI) were calculated. RESULTS: In PCOS, waist circumference and insulin were higher and QUICKI lower than in controls (P<0.01). Trunk fat mass, % trunk fat, and lean mass were higher in PCOS compared to controls (P<0.01), while total bone mass and BMD were similar. IMT was increased in PCOS (P<0.01) but only 15% of PCOS patients had abnormal (> or = 0.9 mm) values. Lean mass correlated with fat parameters, insulin, QUICKI, and FAI, but not with total testosterone; and after adjustments for insulin and QUICKI, lean mass still correlated with fat mass (P<0.01) but not FAI. Lean mass correlated with IMT (P<0.01), but this was dependent on insulin. However, excluding those patients with abnormal IMT values, IMT correlated with lean mass independently of insulin. Bone mass correlated with lean and fat mass, but not with insulin or androgen. PCOS patients with 'pathological' IMT values had higher % trunk fat, lean mass, and insulin, lower QUICKI, and higher testosterone and FAI compared with those with normal IMT. CONCLUSION: Lean mass is increased in PCOS, while bone mass is similar to that of matched controls. The major correlates of lean mass are fat mass and insulin but not androgen. Lean mass also correlated with IMT, and although influenced by insulin, small changes in IMT may partially reflect changes in muscle mass, while clearly abnormal values relate to more severe abnormalities of PCOS.

Endothelial dysfunction in PCOS: role of obesity and adipose hormones.

PURPOSE: Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found. This study was designed to determine if abnormal carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines. METHODS: A prospective study in 50 young women with PCOS (age: 25.2 +/- 1 years; body mass index [BMI]: 28.7 +/- 0.8) and 50 matched ovulatory controls (age: 25.1 +/- 0.7 years; BMI: 28.5 +/- 0.5) was performed. Carotid IMT, brachial FMD, and blood for fasting glucose, insulin, leptin, adiponectin and resistin were measured. RESULTS: PCOS, IMT was increased (P <.01), FMD was decreased (P <.01), fasting insulin was increased (P <.01), QUICKI (a marker of insulin resistance) was decreased (P <.01), and adiponectin was lower (P <.05), whereas leptin and resistin were not different compared with matched controls. Whereas BMI or waist/hip ratios did not correlate with IMT or FMD, insulin and QUICKI correlated positively and negatively with IMT (P <.01). There was a significant negative correlation between adiponectin and IMT (P <.05). These correlations were unchanged when adjusting for BMI and the correlation between IMT and adiponectin was unaffected by insulin resistance parameters. CONCLUSIONS: These data suggest that young women with PCOS have evidence for altered endothelial function. Adverse endothelial parameters were correlated with insulin resistance and lower adiponectin. Both insulin resistance and adiponectin appear to be important parameters. It is hypothesized that the type of fat distribution may influence these factors.

Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS.

OBJECTIVE: Metabolic syndrome (MBS) is a common disorder and is thought to be extremely prevalent in polycystic ovary syndrome (PCOS). In the USA the prevalence of MBS in PCOS has been reported to be as high as 43-46% using Adult Treatment Panel III (ATP-III) criteria. Because of differences in diet, lifestyle and genetic factors, we postulated that the prevalence of MBS might not be as high in Italian women. This study sought to determine the prevalence of MBS in Italian women using both the ATP-III and the World Health Organization (WHO) criteria and to determine whether the prevalence is influenced by the way in which PCOS is diagnosed. DESIGN: Assessment of the prevalence of MBS in 282 women with PCOS, aged 18-40 years, living in western Sicily. Eighty-five age- and weight-matched normal women served as controls. METHODS: Patients were divided into those with chronic anovulation and hyperandrogenism (classic PCOS; n = 225) and others with hyperandrogenism and polycystic ovaries but who were ovulatory (ovulatory PCOS; n = 57). A 75 g oral glucose tolerance test was carried out, as were lipid determinations; insulin resistance was assessed by the Quantitative Insulin-Sensitivity Check Index (QUICKI). We used ATP-III and WHO criteria to diagnose MBS. RESULTS: Using ATP-III criteria, the prevalence of MBS was 8.2% and using WHO criteria it was 16% in Italian women with PCOS. In controls, the prevalence was 2.4% using both methods. In classic PCOS patients, MBS was higher (8.9% by ATP-III, 17.3% by WHO) than in ovulatory PCOS (5% and 10.6% respectively). Body weight significantly modified prevalence rates. CONCLUSION: MBS is substantially higher in women with PCOS than in the general population, and the prevalence is higher in those women diagnosed by classic criteria. However, the prevalence of MBS in PCOS appears to be much lower in Italy than in the USA.

Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism.

CONTEXT: We undertook this study to estimate the prevalence of the various androgen excess disorders using the new criteria suggested for the diagnosis of polycystic ovary syndrome (PCOS). SETTING: The study was performed at two endocrine departments at the University of Palermo (Palermo, Italy). PATIENTS: The records of all patients referred between 1980 and 2004 for evaluation of clinical hyperandrogenism were reevaluated. All past diagnoses were reviewed using the actual diagnostic criteria. To be included in this study, the records of the patients had to present the following available data: clinical evaluation of hyperandrogenism, body weight and height, testosterone (T), free T, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, progesterone, and pelvic sonography. A total of 1226 consecutive patients were seen during the study period, but only the scores of 950 patients satisfied all criteria and were reassessed for the diagnosis. RESULTS: The prevalence of androgen excess disorders was: PCOS, 72.1% (classic anovulatory patients, 56.6%; mild ovulatory patients, 15.5%), idiopathic hyperandrogenism, 15.8%; idiopathic hirsutism, 7.6%; 21-hydroxylase-deficient nonclassic adrenal hyperplasia, 4.3%; and androgen-secreting tumors, 0.2%. Compared with other androgen excess disorders, patients with PCOS had increased body weight whereas nonclassic adrenal hyperplasia patients were younger and more hirsute and had higher serum levels of T, free T, and 17-hydroxyprogesterone. CONCLUSIONS: Classic PCOS is the most common androgen excess disorder. However, mild androgen excess disorders (ovulatory PCOS and idiopathic hyperandrogenism) are also common and, in an endocrine setting, include about 30% of patients with clinical hyperandrogenism.

Evidence for altered adipocyte function in polycystic ovary syndrome.

BACKGROUND: Adipocytokines are produced by adipose tissue and have been thought to be related to insulin resistance and other health consequences. We measured leptin, adiponectin, and resistin simultaneously in women with polycystic ovary syndrome (PCOS) and age- and weight-matched controls. Our hypothesis was that these simultaneous measurements would help determine whether adipocytokine secretion is abnormal in PCOS independent of body mass and whether these levels are related to insulin resistance as well as other hormonal changes. METHODS: Fifty-two women with PCOS and 45 normal ovulatory women who were age- and weight-matched were studied. Blood was obtained for adipocytokines (leptin, adiponectin, and resistin) as well as hormonal parameters and markers of insulin resistance as assessed by the quantitative insulin-sensitivity check index. Body mass index (BMI) was stratified into obese, overweight, and normal subgroups for comparisons between PCOS and controls. RESULTS: Adiponectin was lower (P < 0.05) and resistin was higher (P < 0.05) while leptin was similar to matched controls. Breakdown of the groups into subgroups showed a strong body mass relationship for leptin with no changes in resistin although adiponectin was lower in PCOS, even controlling for BMI. In controls, leptin and adiponectin and leptin and resistin correlated (P < 0.05) but not in PCOS. In controls, all adipocytokines correlated with markers of insulin resistance but not in PCOS. CONCLUSIONS: When matched for BMI status, decreased adiponectin in PCOS represent the most marked change. This alteration may be the result of altered adipose tissue distribution and function in PCOS but no correlation with insulin resistance was found.

Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters.

In hyperandrogenic women, several phenotypes may be observed. This includes women with classic polycystic ovary syndrome (C-PCOS), those with ovulatory (OV) PCOS, and women with idiopathic hyperandrogenism (IHA), which occurs in women with normal ovaries. Where other causes have been excluded, we categorized 290 hyperandrogenic women who were seen consecutively for this complaint between 1993 and 2004 into these three subgroups. The aim was to compare the prevalence of obesity, insulin resistance, and dyslipidemia as well as increases in C-reactive protein and homocysteine in these different phenotypes with age-matched ovulatory controls of normal weight (n = 85) and others matched for body mass index (BMI) with women with C-PCOS (n = 42). Although BMI affected fasting serum insulin and the Quantitative Insulin-Sensitivity Check Index, these markers of insulin resistance were greatest in C-PCOS (n = 204), followed by OV-PCOS (n = 50) and then IHA (n = 33). Androgen levels were similar in OV-PCOS and IHA but were higher in C-PCOS, whereas gonadotropins were similar in all groups. Lipid abnormalities were highest in C-PCOS and OV-PCOS and were normal in IHA. C-reactive protein was elevated in C-PCOS and OV-PCOS but not IHA. Homocysteine was elevated only in C-PCOS. Overall, the prevalence of obesity (BMI > 30) was 29% in C-PCOS, 8% in OV-PCOS, and 15% in IHA and insulin resistance (Quantitative Insulin-Sensitivity Check Index < 0.33) was 68% in C-PCOS, 36% in OV-PCOS, and 26% in IHA. The prevalence of having at least one elevated cardiovascular risk marker was 45% in C-PCOS 38% in OV-PCOS and was not increased on IHA (6%). These results suggest that among hyperandrogenic women the prevalence of abnormal metabolic and cardiovascular risk parameters is greatest in C-PCOS, followed by OV-PCOS and then women with IHA. Moreover, in that in OV-PCOS and IHA, ages and weights were similar yet the prevalence of metabolic and cardiovascular risk was greater in OV-PCOS, the finding of polycystic ovaries may be a significant modifying factor.

[Normalization of the GH response to L-DOPA in acromegalics after treatment with bromocriptine]. / Normalizzazione della risposta in GH al L-DOPA negli acromegalici dopo trattamento con bromocriptina.

The plasma GH response to the L-dopa test (500 mg per os) has been assessed in 7 acromegalics who had never been treated before. Whereas three patients showed an increase in plasma GH, the other four presented a paradoxical response with a significant reduction in plasma GH levels. All subjects were put on to treatment with bromocryptin (10 mg/die). Three months later it was noted that only the four subjects with paradoxical response to L-dopa responded positively to bromocryptin treatment (at least 50% reduction in plasma GH). The L-dopa test was repeated in these four patients. In three of them who presented basal levels of GH lower than 10 ng/ml the L-dopa response curve was found to be reversed. It is concluded that in responsive patients, bromocryptin not only reduces GH levels but also normalizes the response to certain stimuli such as L-dopa.