Efstathios Papadakis

Insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: a prospective study

BACKGROUND Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by oligo- or anovulation (ANOV), biochemical or clinical manifestations of hyperandrogenemia (HA) and PCOs. Four phenotypes of PCOS exist [phenotype 1 (ANOV + HA + PCO), phenotype 2 (ANOV + HA), phenotype 3 (HA + PCO) and phenotype 4 (ANOV + PCO)] but the differences between them are not well studied. We compared markers of insulin resistance (IR) and endocrine characteristics between the different PCOS phenotypes. METHODS We prospectively studied 1212 consecutive women with PCOS and 254 BMI-matched healthy women. RESULTS Phenotypes 1-4 were present in 48.2, 30.7, 9.7 and 11.4% of patients, respectively. BMI did not differ between the four phenotypes and controls. Both normal weight and overweight/obese women with phenotypes 1 and 2 were more insulin resistant than controls. Overweight/obese, but not normal weight, women with phenotype 4 were more insulin resistant than controls, while IR in women with phenotype 3 did not differ from controls regardless of obesity. In normal weight subjects, women with phenotypes 1 and 2 were more insulin resistant than women with phenotype 4. In overweight/obese subjects, women with phenotype 1 were more insulin resistant than women with phenotypes 2 and 3 and women with phenotype 4 were more insulin resistant than those with phenotype 3. Circulating androgens were higher in normal weight and overweight/obese PCOS patients with phenotypes 1-3 compared with those with phenotype 4, and higher in normal weight PCOS patients with phenotype 1 than in those with phenotype 2. CONCLUSIONS Phenotype 1 is associated with more IR and more pronounced HA than phenotype 2. Phenotypes 2 and 4 with obesity, are also characterized by IR. In contrast, phenotype 3 is not associated with IR.

Acute pancreatitis in pregnancy: an overview.

Acute pancreatitis is rare in pregnancy but it is associated with increased incidence of maternal and fetal mortality. It should be considered in the differential diagnosis of upper quadrant abdominal pain with or without nausea and vomiting. The commonest identified causes of acute pancreatitis in pregnancy are gallstones, alcohol and hypertriglyceridemia. The main laboratory finding is increased amylase activity. Appropriate investigations include ultrasound of the right upper quadrant and measurement of serum triglycerides and ionized calcium. Management of gallstone pancreatitis is controversial, although laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) are often used and may be associated with lower complication rates. In hypertriglyceridemia-induced acute pancreatitis ω-3 fatty acids and even therapeutic plasma exchange can be used. We also discuss preventive measures.

Lifestyle intervention and anti-obesity therapies in the polycystic ovary syndrome: impact on metabolism and fertility

Obesity is frequently present in patients with polycystic ovary syndrome (PCOS) and plays an important role in the pathogenesis of the metabolic, endocrine, and reproductive abnormalities associated with this syndrome. We aimed to summarize the effects of lifestyle changes and anti-obesity pharmacotherapy in patients with PCOS. We reviewed the literature regarding the effects of lifestyle changes and anti-obesity agents on the metabolic and endocrine abnormalities of PCOS. Lifestyle changes, including diet, exercise, and behavioral modification, appear to improve the metabolic and reproductive abnormalities of overweight and obese patients with PCOS. Therefore, lifestyle changes appear to represent the first-line management for all overweight and obese patients with PCOS. However, the optimal composition of diet and the optimal type of exercise in these patients are unknown. Anti-obesity agents that have been studied in PCOS include orlistat, sibutramine, and rimonabant. However, the latter two agents have been withdrawn from the market because of side effects. Long-term studies with orlistat in overweight and obese diabetic patients showed greater weight loss and metabolic and cardiovascular benefits than those achieved with lifestyle changes alone. However, there are limited data on the efficacy of orlistat in women with PCOS. In conclusion, lifestyle changes (diet, exercise and behavioral modification), particularly when combined with anti-obesity agents, exert beneficial effects on the endocrine abnormalities of obese patients with PCOS and improve metabolic parameters.

Prevalence of metabolic syndrome in women with polycystic ovary syndrome.

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.

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

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.

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.

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.

Comparison of markers of insulin resistance and circulating androgens between women with polycystic ovary syndrome and women with metabolic syndrome

STUDY QUESTION Do women with the polycystic ovary syndrome (PCOS) differ from those with the metabolic syndrome (MetS) in markers of insulin resistance (IR) and circulating androgens? SUMMARY ANSWER Women with MetS have more pronounced IR than those with PCOS whereas only the latter have elevated circulating androgens. WHAT IS KNOWN ALREADY PCOS and MetS share many similarities, including abdominal obesity and IR, and PCOS is regarded as the ovarian manifestation of MetS. However, there are limited data on the differences between markers of IR and circulating androgens between women with these two syndromes. STUDY DESIGN, SIZE, DURATION A prospective study in 1223 Caucasian women with PCOS and 277 women without PCOS, matched for BMI, was performed between May 2004 and December 2011. The presence/absence of MetS in PCOS+ and PCOS- women was recorded and comparisons among the resulting four groups were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS This study was performed in a university department of obstetrics and gynecology. The following markers of IR were determined: serum glucose and insulin levels, glucose/insulin ratio, area under the oral glucose tolerance test, homeostasis model assessment of IR index and quantitative insulin sensitivity check index. MAIN RESULTS AND THE ROLE OF CHANCE PCOS+MetS+ women (n = 361) were more insulin-resistant than PCOS+MetS- women (n = 862) (P < 0.001 for the comparisons in all markers of IR). Similarly, PCOS-MetS+ women (n = 66) were more insulin-resistant than PCOS-MetS- women (n = 211) (P < 0.001 for the comparisons in all markers of IR). In contrast, PCOS+MetS+ showed only borderline significant differences in some markers of IR compared with PCOS-MetS+ women (P < 0.05). Similarly, PCOS+MetS- women showed only borderline significant differences in some markers of IR compared with PCOS-MetS- women (P = 0.037). Moreover, PCOS-MetS+ women were more insulin-resistant than PCOS + MetS- women (P < 0.001 for the comparisons in all markers of IR). Regarding circulating androgens, PCOS+MetS+ women had higher levels of circulating androgens than PCOS-MetS+ women (P < 0.001 for the comparisons in all circulating androgens). Similarly, PCOS+MetS- women had higher levels of circulating androgens than PCOS-MetS- women (P < 0.001 for the comparisons in all circulating androgens). In contrast, circulating androgens did not differ between PCOS+MetS+ women and PCOS+MetS- women. Similarly, circulating androgens did not differ between PCOS-MetS+ women and PCOS-MetS- women. LIMITATIONS, REASONS FOR CAUTION Only Caucasian women were included in the study. IR was not assessed with the euglycemic hyperinsulinemic clamp. WIDER IMPLICATIONS OF THE FINDINGS Even though MetS and PCOS have many similarities, they are distinct disorders. PCOS does not appear to simply represent the ovarian manifestation of MetS. Further studies are required to assess the contribution of hyperandrogenism to the pathogenesis of IR in PCOS. STUDY FUNDING/COMPETING INTEREST(S) No external funding was either sought or obtained for this study.

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: assessment of non-invasive indices predicting hepatic steatosis and fibrosis.

OBJECTIVEInsulin resistance contributes to the pathogenesis of both polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). The main aim of the present study was the evaluation of non-invasive indices of hepatic steatosis and fibrosis in PCOS women with or without metabolic syndrome (MetS).DESIGNIn this cross-sectional study, three non-invasive indices for hepatic steatosis [NAFLD liver fat score, lipid accumulation product (LAP) and hepatic steatosis index (HIS)] and four for fibrosis [FIB-4, aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI), body mass index (BMI)-Age-Alanine aminotransferase (ALT)-Triglycerides (BAAT) and BMI AST/ALT Ratio Diabetes (BARD)] were calculated in 314 PCOS women (77 with, 237 without MetS) and 78 controls.RESULTSAll steatosis indices were significantly higher in the PCOS than the control group (NAFLD liver fat score: −0.139±0.117 vs. −0.976±0.159, p<0.001; LAP: 43.3±1.9 vs. 34.7±3.1, p = 0.036; HIS: 44.6±0.5 vs. 42.1±0.8, p = 0.016). FIB-4 and BAAT [fibrosis stage (F)2-4] were higher in the PCOS group (0.480±0.020 vs. 0.400±0.013, p<0.001; and 15.6% vs. 5.1%, respectively), whereas APRI and BARD were not. All steatosis indices were significantly higher in PCOS women with than without MetS (NAFLD liver fat score: 1.874±0.258 vs. −0.793±0.099, p < 0.001; LAP: 76.8±4.9 vs. 33.4 ± 1.4, p < 0.001; and HIS: 49.8±1 vs. 43±0.5, p<0.001). Of the fibrosis indices, only BAAT (F2-4: 50.6% vs. 4.2%) was higher in PCOS women with MetS.CONCLUSIONSNon-invasive indices of hepatic steatosis were significantly higher in PCOS, especially in the presence of MetS, whereas indices of hepatic fibrosis yielded controversial results. Further studies are warranted to evaluate the long-term outcomes of hepatic steatosis and fibrosis indices in PCOS women.

Elevated serum androstenedione is associated with a more severe phenotype in women with polycystic ovary syndrome (PCOS)

OBJECTIVETo evaluate the impact of elevated serum Δ4A levels on the hormonal and metabolic features of the different phenotypes of PCOS.DESIGN1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined.RESULTSIn PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), Δ4A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/Δ4A ratio. In the milder phenotype III, a positive correlation between Δ4A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased Δ4A and T/Δ4A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II.CONCLUSIONSIncreased serum Δ4A levels, which are associated with more severe PCOS phenotypes, possibly contribute to the worsening of PCOS features and therefore could be a valuable marker of biochemical hyperandrogenemia.