Cardiovascular risk in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that has received an immense amount of attention in the recent years due to the possible associated risk of cardiovascular disease. Women with PCOS demonstrate an adverse cardiovascular profile characteristic of the cardiometabolic syndrome and an established risk of progression to type 2 diabetes. Despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease, it is unclear if they develop accelerated atherosclerosis. This article summarized the recent development and findings of cardiovascular risk in women with PCOS, and finally the therapeutic options will be discussed.     

Vascular compliance in women with polycystic ovary syndrome and healthy women

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women of reproductive age, has been associated with the cardiometabolic syndrome and increased risk for cardiovascular diseases. Large (C1) and small (C2) vessel compliance and fasting lipids were measured in 45 healthy women and 36 women with PCOS. There were no differences in vacular compliance (C1, C2) between the 2 groups. Systolic blood pressure (116.8 vs 124.3 mm Hg; P=.01), mean arterial pressure (82.5 vs 87 mm Hg; P=.03), and low-density lipoprotein cholesterol (98.1 vs 119 mg/dL; P=.001) were significantly higher in the PCOS group. This difference was not significant after adjusting for age and body mass index. High-density lipoprotein levels in subjects with PCOS were significantly lower than in healthy women (60.2 vs 48.9 mg/dL, P=.02) even after adjusting for age and body mass index. The study indicates that obesity and low high-density lipoprotein are the major contributing factors to cardiovascular changes in PCOS.     

Association between coronary heart disease risk factors and physical fitness in healthy adult women

We examined associations between physical fitness and risk factors for coronary heart disease in healthy women ages 18-65 years. Physical fitness was objectively determined by the duration of a maximal treadmill exercise test. Six physical fitness categories (very poor to superior), specific within 10-year age increments, were established. Mean risk factor levels varied across categories, but so did potential confounders such as age and weight. Multiple linear regression modeling was used to control for the effects of age, weight and year of exam on coronary risk factors. After adjustment, physical fitness was independently associated with triglycerides (p less than 0.001), high-density lipoprotein cholesterol (HDL-C) (p less than or equal to 0.001), total cholesterol/HDL-C ratio (p less than or equal to 0.001), blood pressure (p less than or equal to 0.001) and cigarette smoking (p less than or equal to 0.001).     

Nonalcoholic fatty liver disease in women with polycystic ovary syndrome

BACKGROUND/AIMS: Insulin resistance is a common feature of both nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), therefore, we hypothesize that PCOS and NAFLD may coexist. The aim of the present study was to determine the frequency and characteristics of NAFLD in women with PCOS. METHODS: A prospective study of patients with PCOS and no current pharmacological treatment was conducted. NAFLD was diagnosed by abdominal ultrasound following exclusion of alcohol consumption, viral, or autoimmune liver disease. Anthropometric variables, serum levels of glucose, insulin, lipids and aminotransferases, and HOMA index were determined. RESULTS: Forty-one PCOS patients (mean age: 24.6+/-7.2yr, mean body mass index [BMI]: 30.3+/-7.0kg/m(2)) were included; 26 of 41 PCOS patients (63.4%) had insulin resistance and 17 (41.5%) had NAFLD. Nine of the NAFLD patients (64%) also had abnormal aminotransferases. Women with NAFLD and PCOS had a higher HOMA index and a higher waist-hip ratio than those with normal ultrasound. Patients with PCOS showed a higher frequency of NAFLD (41% vs. 19%) and insulin resistance (63% vs. 35.5%) than a control group. CONCLUSIONS: NAFLD is frequent in patients with PCOS confirming a relevant clinical association between these two conditions. Women with PCOS should be screened for liver disease.     

Smaller LDL particle size in women with polycystic ovary syndrome compared to controls

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. The contribution of lipid abnormalities to this higher risk, in particular atherogenic modifications of low density lipoprotein (LDL) such as a shift towards smaller LDL, has not been properly explored. We aimed to examine LDL size variation in relation to androgens and other risk factors in women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in women with PCOS and women with normal ovarian function, of similar age and body mass index (BMI). PATIENTS: Thirty-one women with PCOS and 27 controls were studied. Patients were recruited from the outpatient endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides (TG), high density lipoprotein (HDL), LDL, glucose, insulin, gonadotrophins, androgens, oestradiol, 17 OH progesterone and SHBG were measured. LDL particle diameter was calculated based on distance travelled in polyacrylamide native gels. Recumbent blood pressure was measured automatically. RESULTS: LDL particle size appeared to be significantly smaller in hyperandrogenic PCOS as compared to regularly cycling women (P = 0006), independent of variations in lipid levels. SHBG was the only independent predictor of LDL size in this population, with a strong correlation, which persisted after adjustment for all confounding variables. CONCLUSIONS: Our results suggest that androgen excess and mild insulin-resistance (both responsible for lower SHBG) may have an early modifying effect on low density lipoprotein size in polycystic ovary syndrome women. The denser pattern observed in polycystic ovary syndrome women could by itself constitute a higher cardiovascular risk, even in the absence of overt dyslipidaemia, and contribute to the excess risk of cardiovascular disease reported in this syndrome.     

多囊卵巢综合征患者代谢综合征患病风险研究

目的 研究多囊卵巢综合征(PCOS)患者代谢综合征(MS)患病率,并探讨MS发生的危险因素.方法 比较348例年轻的PCOS患者及113名非PCOS正常女性的MS及其组分的患病率.结果 PCOS组MS的患病率为27.0%,明显高于正常对照组的10.6%(P<0.01),除甘油三酯外,其他MS组分在PCOS组均高于正常对照组(P<0.05或P<0.01),但校正年龄和体重指数(BMI)后,差异就不存在统计学意义(P=0.737).分层分析也显示PCOS非肥胖组和肥胖组的MS患病率与相应的正常对照组均无明显差异(均P>0.05).多元逐步回归分析显示稳态模型评估的胰岛素抵抗指数(HOMA-IR)和BMI是MS的独立预测因素(均P<0.01).结论 肥胖和胰岛素抵抗是MS的独立危险因素,PCOS单独并不增加MS的发生风险.     

Coronary artery disease in premenopausal Indian women: risk factors and angiographic profile.

Coronary angiographic and clinical profile of 47 premenopausal women presenting with myocardial infarction (MI) or angina is presented. Seventeen patients (36%) had significant obstructive coronary artery disease (CAD) (Group I), while 30 (64%) had normal coronaries (Group II). The latter group included 4 who had MI and 26 who presented with angina. Risk factors in Group I included hypertension (53%), diabetes mellitus (24%), hypercholesterolemia (29%), oral contraceptives and a positive family history (11.8%). Frequency of one, two and three vessel disease was 47%, 18% and 35% respectively. The left anterior descending artery was most commonly affected (82%). In Group II the risk factors included hypertension (17%) and diabetes (7%). No patient in either group was a smoker. This analysis shows that significant obstructive CAD in premenopausal Indian females is more commonly associated with hypertension, diabetes and hypercholesterolemia. Smoking was not encountered and ingestion of contraceptive pills is uncommon.     

Stability of adrenocortical steroidogenesis over time in healthy women and women with polycystic ovary syndrome

Adrenocortical secretion is up-regulated in women with polycystic ovary syndrome (PCOS), and absolute adrenal androgen (AA) excess is evident in approximately 25% of these patients. We hypothesized that AA biosynthesis is an inherited trait and that, as for other inherited traits, AA biosynthesis remains stable over time. To test this hypothesis, we prospectively studied 23 off-treatment PCOS patients and seven age- and body mass index-matched control women on two separate occasions 3-5 yr apart (45.0 +/- 19.0 months and 47.4 +/- 21.3 months, respectively; P > 0.05). All subjects underwent an acute adrenal stimulation using 0.25 mg ACTH-(1-24), and dehydroepiandrosterone (DHEA), androstenedione, and cortisol (F) were measured 0 and 60 min post ACTH; basal levels of total and free testosterone (T), SHBG, and DHEA sulfate (DHEA-S) were also assessed. Among PCOS patients, the mean DHEA-S levels during the repeat study were significantly lower when compared with the initial assessment (170 +/- 107 microg/dl vs. 134 +/- 79 microg/dl, respectively; P = 0.02). However, only patients with initial DHEA-S levels above the median (high DHEA-S) experienced a net decrease in the levels of this metabolite (252.5 +/- 99.2 microg/dl vs. 174.3 +/- 82.5 microg/dl; P = 0.001) over the time of the study; patients with initial DHEA-S levels in the lower half (low DHEA-S) did not experience a change in DHEA-S (94.6 +/- 28.9 microg/dl vs. 97.7 +/- 56.5 microg/dl; P = 0.85). In patients, the total T levels tended to be higher at the second study, although SHBG levels were also higher, resulting in unchanged free T levels over time. Among controls, no significant changes in basal androgens were observed over the time of the study. There were no significant differences in either the basal or ACTH-stimulated levels of DHEA, androstenedione, or F over the time of the study in either PCOS or control women. We conclude that the adrenocortical secretion of AAs or F in PCOS and control women remains stable over time, supporting the hypothesis that the adrenal response to ACTH may be an inherited trait. Alternatively, a decrease in DHEA-S levels over time was observed but only among PCOS patients whose initial levels of this metabolite were above the group median, suggesting that the activity of sulfotransferase in these patients may be up-regulated by factors other than those affecting adrenocortical biosynthesis and that such regulatory influences attenuate over time.     

Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome

Twenty-nine patients with polycystic ovary syndrome (PCOS) and 30 normal women had lipoprotein lipid and androgen profiles compared after a 12-h fast. Both PCOS and normal women were evaluated in the proliferative phase of the cycle. PCOS patients had higher serum LH to FSH ratios [2.0 +/- 1.3 (+/- SEM) vs. 0.6 +/- 0.1), higher testosterone (T; 66 +/- 5 vs. 33 +/- 2 ng/ml), higher free T (1.1 +/- 1 vs. 0.4 +/- 0.02 ng/dl), and higher dehydroepiandrosterone sulfate (291 +/- 28 vs. 140 +/- 12 micrograms/dl) levels, and lower T-estrogen-binding globulin-binding capacity (1.5 +/- 0.2 vs. 2.2 +/- 0.1 micrograms/dl) than normal women (all P less than 0.05). The PCOS patients had higher mean serum triglycerides [122 +/- 11 (+/- SEM) 63 +/- 3 mg/dl] and very low density lipoprotein cholesterol levels (24 +/- 2 vs. 13 +/- 1 mg/dl), but lower high density lipoprotein cholesterol levels (43 +/- 2 vs. 58 +/- 2 mg/dl; P less than 0.05). While PCOS patients were heavier and more sedentary and their diets were higher in saturated fat and lower in fiber (P less than 0.01, respectively), the differences in lipoprotein lipid concentrations could not be attributed to body weight. T-estrogen-binding globulin-binding capacity correlated with high density lipoprotein cholesterol in PCOS patients (r = 0.42; P = 0.025) after adjusting for weight. We conclude that hyperandrogenemia in women may result in a male pattern of lipoprotein lipid concentrations. These findings suggest that PCOS patients may have increased atherogenic potential.     

绝经期前女性冠心病患者冠脉病变特点及其危险因素分析

目的：观察绝经期前女性冠心病（CHD）患者冠状动脉病变特点及其危险因素。方法：入选绝经期前女性冠心病患者102例作为观察组,平均（48.2±7.5）岁,同时入选同年龄段CHD男性及非CHD女性患者各100例作为对照组,所有患者均行常规生化,心电图,超声心动图以及冠状动脉造影检查。结果：与CHD男性患者比较,绝经期前CHD女性有糖尿病史者比例明显升高（18.0%比27.5%）,而吸烟者（31.0%比12.7%）、患ST段抬高心肌梗死比例（15.0%比2.9%）明显减小,左室射血分数（LVEF）明显降低[（59.7±9.8）%比（52.8±8.5）%],C型病变（32.0%比56.9%）,Gensini积分≥40的病例（32.0%比44.1%）明显增多,P均〈0.05。与非CHD女性相比,高血压（32.0%比52.9%）,糖尿病患病率（9.0%比27.5%）及C反应蛋白水平[（11.35±8.35）mg/L比（16.40±6.49）mg/L]明显升高,LVEF[（59.9±5.3）%比（52.8±8.5）%]显著降低,P均〈0.05。结论：绝经期前女性冠心病患者冠状动脉病变较重,临床风险较高。     

Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome

OBJECTIVE: The evidence that some women with the polycystic ovary syndrome (PCOS) are hyperinsulinaemic has brought into question their risk of developing early coronary artery disease. We have focused on three cardiac risk factors which have been associated with hyperinsulinaemia by measuring glucose tolerance, fasting serum lipid concentrations and blood pressure in women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in lean and obese women with PCOS and in women with normal ovaries. Determinants of the risk factors for coronary artery disease were assessed by multiple regression analysis. PATIENTS: One hundred and two women with ultrasound diagnosed PCOS and 19 lean women with normal ovaries were studied. Patients were recruited from a reproductive endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides, high density lipoproteins (HDL), HDL2, glucose tolerance, fasting and stimulated insulin, gonadotrophins, testosterone and androstenedione were measured during a 2-hour oral glucose tolerance test. Recumbent blood pressure was measured automatically. RESULTS: Lean women with PCOS were found to be hyperinsulinaemic and have reduced serum HDL and HDL2 concentrations compared to women with normal ovaries; serum insulin concentrations correlated positively with plasma glucose and blood pressure measurements in multiple regression analysis. Obese women with PCOS were in addition found to have higher systolic blood pressure, serum triglyceride and plasma glucose concentration than lean women with PCOS and controls. CONCLUSIONS: These results support the evidence that hyperinsulinaemic women with PCOS have an increased risk of developing cardiovascular disease and therefore form a population in whom metabolic screening is advisable.     

Prevalence of an immunological LH β-subunit variant in a UK population of healthy women and women with polycystic ovary syndrome

OBJECTIVE An Immunological LH β-subunit variant has been described, which is undetectable using monoclonal antibodies directed to the intact LH molecule alone. Subjects have been found homozygous or heterozygous for nucleotide mutations within codons 8 and 15 in the LH β-subunit gene. The prevalence of the variant LH β-subunit has been estimated in a healthy UK population of women of reproductive age and in women with polycystic ovary syndrome (PCOS). The relationship of the variant molecule to the clinical and hormonal parameters of the subjects has been evaluated. DESIGN The control and PCOS subjects were screened for the presence of the mutation by using a ratio of two immunofluorometric assays using monoclonal antibodies (Mab). One assay, not detecting the LH variant, uses a Mab directed to the intact LH molecule and a β-specific Mab. The other assay, detecting both the variant and wildtype LH, uses two β-subunit specific Mabs. The mutations in the LH β-subunit gene were confirmed by restriction fragment length polymorphism. The relationship of the presence of the variant to the clinical and hormonal parameters was assessed by ANOVA. PATIENTS Two hundred and twelve normal ovulatory women, of whom 86 (31%) were obese (body mass Index >25) and 146 (69%) non-obese, and 153 women with PCOS, 115 (75%) obese and 38 (25%) non-obese participated in the study. RESULTS The variant LH was detected In 31 (15%) controls and 32 (21%) PCOS subjects (P=0.124) using specific Mab. Obese PCOS had a higher incidence of the heterozygous LH variant compared to obese controls (odds ratio 2.5, P=0.03), and compared to non-obese PCOS (odds ratio 6.3, P= 0.01). The previously described two mutations in codon 8 and codon 15 were present in all subjects detected to be mutant hetero or homo-zygous by RFLP. There was no relationship between the presence of the variant LH and the clinical and hormonal parameters In the PCOS subjects; however, in the controls the presence of the variant LH was associated with a higher serum total testosterone (P=0.046), oestradiol (P=0.03) and SHBG (P=0.002). CONCLUSIONS The results of this study show that the variant LH β-subunit is a common polymorphism occurring in 15% of a healthy UK population of women. The prevalence was not higher in women with PCOS, though it was over represented in obese women with PCOS. The presence of the variant did not alter the clinical or hormonal expression of the disorder in women with PCOS. Its presence in the controls was however associated with higher serum oestradiol and probably secondary elevation of SHBG and testosterone, suggesting that the variant form of LH may be associated with subtle changes in the function of the hypothalamic-pituitary-gonadal axis.     

Insulin sensitivity in women with polycystic ovary syndrome

The aim of our study was to compare insulin sensitivity in lean and obese European polycystic ovary syndrome (PCOS) women with lean healthy women. We performed the euglycemic hyperinsulinemic clamp in 83 women with PCOS [53 lean with body mass index (BMI) of 21.5 +/- 1.8 kg/m2 and 30 obese with BMI of 29.6 +/- 3.7 kg/m2] and in 15 healthy women with BMI of 21.6 +/- 1.8 kg/m2 to determine glucose disposal (M) and the insulin sensitivity index (ISI). Statistical evaluation was done using Kruskal-Wallis ANOVA followed by Kruskal-Wallis multiple-comparison z-value test. The basal blood glucose was significantly higher in lean and obese PCOS women than in controls (P < 0.02). Fasting insulin was significantly higher in both lean and obese PCOS women than in controls (P < 0.000001). Obese PCOS women were more insulin resistant than controls (P < 0.02 for M and P < 0.0008 for ISI); lean PCOS women did not differ from controls in M or ISI. Posthepatic insulin delivery was significantly higher in both lean and obese PCOS women compared with controls (P < 0.000008). We conclude that lean PCOS women are not more insulin resistant than healthy controls. Insulin hypersecretion, on the other hand, is present even in lean PCOS women.