Associations of menstrual cycle irregularities with age, obesity and phenotype in patients with polycystic ovary syndrome.

OBJECTIVE: Limited data suggest that menstrual cycle abnormalities are more pronounced in younger and more obese patients with polycystic ovary syndrome (PCOS). We aimed to evaluate the association between menstrual cycle pattern and age, obesity and PCOS phenotype in a large population of women with PCOS. DESIGN: We studied 1,297 women with PCOS and divided them according to: a) age in ≤ 20, 21-30 and > 30 years old, b) body mass index in normal weight, overweight and obese and c) PCOS phenotype in phenotype 1 (anovulation, hyperandrogenemia and polycystic ovaries), 2 (anovulation and hyperandrogenemia without polycystic ovaries), 3 (hyperandrogenemia and polycystic ovaries without anovulation) and 4 (anovulation and polycystic ovaries without hyperandrogenemia). RESULTS: The proportion of women with regular menstrual cycles progressively increased in the older age groups, being 8.1, 10.5 and 12.7% in women ≤ 20, 21-30 and > 30 years old, respectively (p = 0.037). The proportion of women with regular menstrual cycles did not differ between normal weight and obese women but was higher in overweight women (9.3, 9.4 and 13%, respectively; p = 0.020). The proportion of women with regular cycles alternating with irregular cycles was highest in women with phenotype 4, intermediate in women with phenotype 2 and lowest in women with phenotype 1 (74.3, 69.4 and 61.7%, respectively; p = 0.027). CONCLUSIONS: Menstrual cycle pattern is more irregular in women with the "classic" PCOS phenotypes than in phenotype 4 but appears to normalize with ageing. On the other hand, obesity does not appear to have an important effect on menstrual cycle pattern in PCOS.

The role of orlistat combined with lifestyle changes in the management of overweight and obese patients with polycystic ovary syndrome.

OBJECTIVE: Obesity is frequently present in women with the polycystic ovary syndrome (PCOS) and aggravates insulin resistance (IR) and hyperandrogenemia. We aimed to assess the effects of orlistat combined with lifestyle changes in overweight and obese women with PCOS and body mass index (BMI)-matched controls. DESIGN: Prospective study. PATIENTS: We studied 101 women with PCOS (age 26·1 ± 6·4 years, BMI 34·5 ± 5·9 kg/m(2) ) and 29 BMI-matched women with normal ovulating cycles. All women were instructed to follow a low-calorie diet to exercise and were treated with orlistat 120 mg tid for 6 months. MEASUREMENTS: Metabolic and endocrine characteristics of PCOS, blood pressure (BP) and lipid profile. RESULTS: A significant and comparable reduction in BMI was observed in women with PCOS and controls. Systolic and diastolic BP decreased only in women with PCOS. Serum low-density lipoprotein cholesterol levels decreased in both women with PCOS and controls; however, this reduction was greater in controls. In contrast, serum high-density lipoprotein cholesterol levels did not change in women with PCOS and decreased in controls. Serum triglyceride levels decreased significantly and to a comparable degree in the two groups. Similarly, markers of IR improved significantly and to a comparable degree in women with PCOS and controls. Serum testosterone levels and the free androgen index decreased significantly in women with PCOS and did not change in controls. CONCLUSIONS: Orlistat combined with lifestyle changes induces substantial weight loss in women with PCOS, resulting in improvements in IR, hyperandrogenemia and cardiovascular risk factors.

Age- and body mass index-related differences in the prevalence of metabolic syndrome in women with polycystic ovary syndrome.

AIM: To compare the prevalence of metabolic syndrome (MetS) between women with polycystic ovary syndrome (PCOS) and controls across different age (≤20, 21-30 and 31-39 years old) and body mass index (BMI) (normal weight, overweight and obese) groups. METHODS: We studied 1223 women with PCOS and 277 BMI-matched controls. The prevalence of MetS in women with PCOS and controls was estimated according to four different MetS definitions. RESULTS: In subjects ≤20 and 21-30 years old, the prevalence of MetS did not differ between women with PCOS and controls regardless of the MetS definition, even though women with PCOS were more obese than controls in the ≤20 years old group. In subjects 31-39 years old, the prevalence of MetS was higher in women with PCOS than in controls but the former were more obese than controls. The prevalence of MetS did not differ significantly between women with PCOS and controls in any of the BMI groups (normal weight, overweight or obese) regardless of the MetS definition. CONCLUSION: The prevalence of Mets appears to be primarily determined by obesity and age whereas PCOS per se appears to be a less important contributing factor.

The clinical significance and primary determinants of hirsutism in patients with polycystic ovary syndrome.

OBJECTIVE: Hirsutism is frequently present in patients with polycystic ovary syndrome (PCOS) and is a major sign of hyperandrogenism. However, other disorders frequently present in PCOS, particularly abdominal obesity and insulin resistance (IR), have also been implicated in the development of hirsutism in this population but relevant data are limited. We aimed to define the determinants of the presence of hirsutism in PCOS. DESIGN: Observational study. METHODS: We studied 1297 patients with PCOS (age 24.3±5.8 years, BMI 26.8±6.9 kg/m(2)). Hirsutism was defined as a modified Ferriman-Gallwey score ≥8. RESULTS: Women with hirsutism were younger, had greater BMI, and had higher levels of circulating androgens than women without hirsutism; markers of IR did not differ between the two groups after adjustment for age and BMI. The prevalence of hirsutism progressively declined with age, was lower in normal-weight women than in overweight and obese women, and was comparably prevalent in the hyperandrogenemic phenotypes of PCOS. In binary logistic regression analysis, independent predictors of the presence of hirsutism were younger age, larger waist circumference (W), and higher serum testosterone levels. In stepwise linear regression analysis, the Ferriman-Gallwey score independently correlated with age, W, free androgen index, and serum Δ4-androstenedione and DHEAS levels. CONCLUSIONS: Besides hyperandrogenemia, abdominal obesity, and young age are independently associated with the presence of hirsutism. In contrast, the relationship between IR and hirsutism appears to be mediated by the more severe obesity of insulin-resistant patients with PCOS.

Prevalence of metabolic syndrome in women with polycystic ovary syndrome.

OBJECTIVE: The polycystic ovary syndrome (PCOS) and the metabolic syndrome (MetS) are common disorders that share many characteristics, particularly abdominal obesity and insulin resistance. Our objective was to compare the prevalence of MetS between a large cohort of patients with PCOS and body mass index -matched controls. DESIGN: Cross-sectional study. PATIENTS: We studied 1223 patients with PCOS and 277 healthy women. Diagnosis of PCOS was based on the revised Rotterdam criteria. Women with PCOS were divided into those who fulfilled both the Rotterdam criteria and the diagnostic criteria of the 1990 National Institutes of Health definition of PCOS (group 1, n = 905) and into those with the additional phenotypes introduced by the Rotterdam criteria (group 2, n = 318). Diagnosis of MetS was based on four different definitions. MEASUREMENTS: Anthropometric, metabolic, hormonal and ultrasonographic features of PCOS. RESULTS: The prevalence of metabolic syndrome (MetS) was higher in women with PCOS than in controls when the National Cholesterol Education Program Adult Treatment Panel III definition of MetS was applied (15·8% and 10·1%, respectively; P = 0·021) but not with the three more recent MetS definitions. The prevalence of MetS was higher in group 1 than in controls regardless of the applied MetS definition. In contrast, the prevalence of MetS was similar in group 2 and in controls regardless of the applied MetS definition. In logistic regression analysis, PCOS did not predict the presence of MetS. CONCLUSIONS: Polycystic ovary syndrome per se does not appear to increase the risk of MetS independent of abdominal obesity.

Association between menstrual cycle irregularities and endocrine and metabolic characteristics of the polycystic ovary syndrome.

OBJECTIVE: Insulin resistance (IR) is frequent in polycystic ovary syndrome (PCOS) and contributes to the increased risk for type 2 diabetes mellitus and cardiovascular disease of this population. Several markers of IR are used but most are expensive or have limited sensitivity and specificity. Preliminary data suggest that the menstrual cycle pattern correlates with IR in PCOS but existing studies are small. We aimed to assess the relationship between the type of menstrual cycle irregularities and IR in PCOS. DESIGN: Prospective study. METHODS: We studied 1285 women with PCOS, divided according to the menstrual cycle pattern. RESULTS: Patients with isolated secondary amenorrhea and those with secondary amenorrhea alternating with regular menstrual cycles were more insulin resistant than patients with regular cycles (Group D). Patients with isolated oligomenorrhea were also more insulin resistant than Group D. However, patients with oligomenorrhea alternating with regular cycles, secondary amenorrhea, or polymenorrhea had comparable levels of markers of IR with Group D. Moreover, patients with oligomenorrhea alternating with regular cycles were less insulin resistant than patients with secondary amenorrhea alternating with regular cycles. Finally, patients with isolated polymenorrhea and those with polymenorrhea alternating with regular cycles had comparable levels of markers of IR with Group D. CONCLUSIONS: Amenorrhea is associated with more pronounced IR in PCOS, and oligomenorrhea portends a less excessive risk for IR than amenorrhea whereas polymenorrhea appears to be even more benign metabolically. Therefore, the type of menstrual cycle abnormality appears to represent a useful tool for identifying a more adverse metabolic profile in PCOS.

Disparate effects of pharmacotherapy on plasma plasminogen activator inhibitor-1 levels in women with the polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by obesity and insulin resistance (IR), which result in elevated plasminogen activator inhibitor-1 (PAI-1) levels. We aimed to assess the changes in PAI-1 levels in PCOS during treatment with metformin and during weight loss. DESIGN: Twenty-three normal weight women with PCOS were given metformin 850 mg bid for 6 months. Fifty overweight/obese women with PCOS were prescribed an energy-restricted diet, were instructed to exercise and were randomized to orlistat 120 mg tid or sibutramine 10 mg qd for 6 months. RESULTS: In normal weight women, treatment with metformin reduced the body mass index (BMI) and circulating androgens, improved markers of IR and lowered PAI-1 levels. In overweight/obese women, sibutramine and orlistat yielded comparable reductions in BMI and markers of IR. In contrast, the effects on the free androgen index (FAI) differed (p=0.027): sibutramine reduced the FAI (p=0.005), whereas orlistat had no effect. The effects of sibutramine and orlistat on PAI-1 levels also differed (p=0.042): sibutramine reduced PAI-1 levels (p<0.001), whereas orlistat had no effect. CONCLUSIONS: Metformin and sibutramine, but not orlistat, reduce PAI-1 levels in PCOS. The reduction in circulating androgens during metformin and sibutramine treatment might be implicated in this decline.

Plasma von Willebrand factor antigen levels are elevated in the classic phenotypes of polycystic ovary syndrome.

OBJECTIVE: We aimed to assess plasma Von Willebrand factor (vWF) levels in women with polycystic ovary syndrome (PCOS) and to compare these levels among the different PCOS phenotypes. DESIGN: We studied 140 women with PCOS and 40 age and body mass index (BMI)- matched healthy women (control group). RESULTS: Plasma vWF antigen levels were higher in women with PCOS than in controls (p=0.017). Plasma vWF antigen levels were also higher in patients with phenotypes 1 [i.e. with anovulation (ANOV), biochemical hyperandrogenemia or clinical manifestations of hyperandrogenemia (HA) and polycystic ovaries (PCO)] and 2 (i.e. with ANOV and HA but without PCO) than in controls (p=0.017). In contrast, plasma vWF antigen levels did not differ between controls and patients with phenotypes 3 (i.e. with HA and PCO but without ANOV) and 4 (i.e. with ANOV and PCO but without HA) or between patients with phenotypes 1 and 2 and patients with phenotypes 3 and 4. When overweight/obese and normal weight subjects were analyzed separately, plasma vWF antigen levels did not differ between patients with PCOS (regardless of phenotype) and controls. CONCLUSIONS: Plasma vWF levels are elevated in women with PCOS. This increase appears to be more pronounced in women with phenotypes 1 and 2 of PCOS. Given the association between vWF levels and increased incidence of cardiovascular events, the evaluation of vWF levels in women with PCOS might be helpful for cardiovascular risk stratification, but prospective studies are needed to support this hypothesis.

Circulating platelet-derived microparticles are elevated in women with polycystic ovary syndrome diagnosed with the 1990 criteria and correlate with serum testosterone levels.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) appear to have higher cardiovascular risk than healthy population. Patients diagnosed with PCOS according to the 1990 criteria have a more adverse metabolic profile than those diagnosed with the 2003 criteria. Platelet-derived microparticles (PMPs) appear to contribute to atherosclerosis but have not been assessed in PCOS. The aim of this study was to determine plasma PMPs in PCOS patients. Design A cross-sectional study. METHODS: We assessed plasma PMPs in 76 normal weight women with PCOS (39 belonging to the phenotypes 1 and 2 (group I) and 37 belonging to the phenotypes 3 and 4 (group II)) and 21 healthy normal weight women. RESULTS: Markers of obesity and insulin resistance did not differ between women with PCOS and controls. Serum testosterone levels and the free androgen index (FAI) were higher in group I than in group II and controls (P<0.001 for all comparisons) but did not differ between the latter two groups. Plasma PMPs were higher in group I than in controls (P=0.018) but did not differ between group II and controls or between groups I and II. In the total study population (n=97), plasma PMPs correlated with serum testosterone levels (r=0.207, P=0.042) and the FAI (r=0.207, P=0.042). CONCLUSIONS: Plasma PMPs are elevated in women with phenotypes 1 and 2 of PCOS compared with healthy controls, but not in women with phenotypes 3 and 4. Hyperandrogenemia, which is more pronounced in phenotypes 1 and 2, appears to be implicated in the increase in plasma PMPs.