Ilias Katsikis

Anti-Müllerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels

The objective of the study was the comparison of anti-Müllerian hormone (AMH) levels among obese or overweight and normal-weight women with the four different polycystic ovary syndrome (PCOS) phenotypes and healthy control subjects. AMH levels were evaluated in four age- and body mass index (BMI)-matched groups of 25 normal-weight and 25 obese or overweight women each, belonging to the four main subsets of the syndrome resulting from combinations of the three diagnostic criteria [group 1: oligo- and/or anovulation (ANOV), hyperandrogenemia (HA), and polycystic ovaries (PCO) on ultrasonographic evaluation; group 2: ANOV and HA; group 3: HA and PCO, group 4: ANOV and PCO], and in 50 (25 obese or overweight and 25 normal weight) age- and BMI-matched healthy control subjects. Age, BMI, waist circumference, FSH, LH, prolactin, testosterone, Delta(4)-androstenedione, dehydroepiandrosterone-sulfate, 17alpha-OH-progesterone, fasting insulin, glucose, AMH, free androgen index, and homeostasis model assessment for insulin resistance index were analyzed. AMH levels were significantly higher in PCOS groups 1 and 2 compared with groups 3 and 4 and the control group and higher in PCOS groups 3 and 4 compared with the control group. AMH levels were significantly increased in normal-weight compared with obese and overweight women. AMH concentrations were independently predicted, in order of significance, by LH and testosterone levels, BMI (negatively), and the total number of follicles 2-9 mm in diameter. The differences in circulating AMH levels between the main phenotypic groups of PCOS women appear to reflect the severity of the syndrome, but are negatively affected by obesity. Increased LH levels might be the most significant independent link between PCOS-associated disorders of ovulation and the observed increase in circulating AMH concentration.

Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS).

Background  Nonenzymatic advanced glycation and oxidation end‐products, advanced glycation end‐products (AGEs), impart a potent impact on vessels and other tissues in diabetic state and in euglycaemic conditions with increased oxidative stress.

Inflammatory and endothelial markers in women with polycystic ovary syndrome

Background  Women with polycystic ovary syndrome (PCOS) carry a pattern of cardiovascular risk factors. Endothelial dysfunction and chronic inflammation are early findings in the atherosclerotic process. The purpose of the study was to investigate the coexistence of active inflammation markers and endothelial dysfunction in young women with PCOS, and their relationship with metabolic and hormonal abnormalities of the syndrome.

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.

Adenomyosis: what is the impact on fertility?

Purpose of review This review is timely and relevant for several reasons. The incidence of adenomyosis begins to rise from the mid-thirties. Moreover, more women are delaying their first pregnancy until later in their thirties or forties, and consequently adenomyosis is encountered more frequently in the fertility clinic during diagnostic work-up. Furthermore, it is difficult to diagnose adenomyosis before surgery, because there are no pathognomonic signs, symptoms or physical findings. Finally, reference data are very limited. Recent findings This review refers to adenomyosis of the uterus as a factor in female infertility. The clinical presentation of adenomyosis uteri is also reviewed, as well as animal and human studies concerning the effect of adenomyosis in female infertility. Different treatment options are discussed, especially those referring to patients who wish to maintain their fecundity. Summary Uterine adenomyosis remains a fairly frequent and debilitating disease that will be encountered with increasing incidence in the infertile female population. While spectacular advances have been made in recent years in the non-invasive diagnosis of the condition, non-surgical treatment options for infertile patients with adenomyosis arise but need to be confirmed in larger series.

Anti-mullerian hormone is associated with advanced glycosylated end products in lean women with polycystic ovary syndrome

OBJECTIVE Oocyte maturation process characterizes polycystic ovary syndrome (PCOS). The mechanisms of this abnormality leading to chronic anovulation are under investigation. Advanced glycosylated end products (AGEs), a marker of oxidative stress linked with oocyte maturation are localized in granulosa cells and are increased in sera, in women with PCOS. The aim of this study was to investigate the relationship, whether there is an association between the anti-mullerian hormone (AMH), a hormone produced by granulosa cells and AGEs in ovulatory and anovulatory PCOS (PCOS-Anov), as well as in non-PCOS anovulatory (Non-PCOS Anov) women. Design Cross-sectional study. METHODS Data from sixty women with PCOS (37 anovulatory and 23 regularly ovulating) were compared with eleven Non-PCOS Anov women and 25 normal women. In each subject biochemical, hormonal, and ultrasonographic parameters were studied. RESULTS AMH values were statistically significantly higher in PCOS-Anov (7.63+/-3.12) in comparison with ovulatory PCOS (PCOS-Ov; 4.92+/-2.50), Non-PCOS Anov (3.66+/-1.4), and controls (4.02+/-1.27 ng/ml). AGEs demonstrated a similar pattern: 8.70+/-1.65 in PCOS-Anov, 7.43+/-1.79, PCOS-Ov, 5.21+/-0.09, Non-PCOS Anov, and 5.85+/-0.89 U/ml in controls (P<0.005 for all comparison respectively). Follicle number was significantly higher in PCOS-Anov in comparison with other groups. A significant positive correlation between AMH and AGEs was observed (r: 0.326, P<0.01), and with the estimated AMH/AGEs ratio to follicle number (r: 0.42, P: 0.0001) and the presence of anovulation. CONCLUSIONS These data suggest that an oxidative marker, AGEs, and AMH, may interact in the anovulatory mechanisms in women with PCOS.

Effect of long-term orlistat treatment on serum levels of advanced glycation end-products in women with polycystic ovary syndrome

Background  Women with polycystic ovary syndrome (PCOS) exhibit elevated serum advanced glycation end‐products (AGE) compared with healthy subjects. Short‐term administration of orlistat has been shown to reduce the postmeal increase in serum AGE levels in women with PCOS and in controls.

Plasma visfatin levels in normal weight women with polycystic ovary syndrome

BACKGROUND The present study was designed to measure plasma visfatin levels in normal weight women with polycystic ovary syndrome (PCOS) and to assess possible correlations between visfatin and the hormonal or metabolic parameters of the syndrome. METHODS Twenty-five normal weight [body mass index (BMI)<25 kg/m(2)] women with PCOS, 24 obese and overweight (BMI>25 kg/m(2)) controls (ovulating women without clinical or biochemical hyperandrogenism), and 24 normal weight controls were studied. Blood samples were collected between the 3rd and the 7th days of a menstrual cycle in the control groups and during a spontaneous bleeding episode in the PCOS groups at 9:00 A.M., after an overnight fast. Circulating levels of LH, FSH, prolactin (PRL), testosterone (T), Delta(4)-androstenedione (Delta(4)-Alpha), dehydroepiandrosterone sulfate (DHEA-S), 17alpha-OH-progesterone (17OH-P), sex hormone-binding globulin (SHBG), insulin, glucose, and visfatin were measured. RESULTS Plasma visfatin levels and the visfatin-to-insulin ratio were significantly lower in normal weight controls than in both normal weight women with PCOS and overweight or obese controls. The visfatin-to-insulin ratio was significantly higher in normal weight women with PCOS than in overweight or obese controls. Plasma visfatin levels were found to be positively correlated with LH and Delta(4)A levels, as well as with free androgen index (FAI) values, and negatively correlated with SHBG. LH and SHBG levels were found to be the only independent significant determinants of circulating visfatin. In the control groups, plasma visfatin levels were significantly correlated with BMI, waist (W) measurement, and waist-to-hip ratio (WHR). CONCLUSIONS Visfatin levels are positively associated with obesity in healthy women of reproductive age. Moreover, the present study indicates, for the first time, a possible involvement of increased visfatin levels in PCOS-associated metabolic and hormonal disturbances.

The impact of oral contraceptives and metformin on anti-Müllerian hormone serum levels in women with polycystic ovary syndrome and biochemical hyperandrogenemia

Objective. To assess the impact of metformin and of two different oral contraceptives (OCs) containing cyproterone acetate and drospirenone, on serum anti-Müllerian hormone (AMH) levels, in a cohort of women with polycystic ovary syndrome (PCOS) with hyperandrogenism. Design. Prospective randomised study. Setting. Division of Endocrinology and Human Reproduction, Aristotle University of Thessaloniki. Patients. Forty-five (45) women with PCOS diagnosed according to the criteria proposed in 1990 by the NIH. Interventions. Women with PCOS were randomised into three groups, all treated for 6 months: Group A received an OC containing 35 μg ethinylestradiol plus 2 mg cyproterone acetate, Group B received an OC containing 30 μg ethinylestradiol plus 3 mg drospirenone and Group C received metformin 850 mg × 2. Main outcome measure(s). Anti-Müllerian hormone levels were measured by a specific ELISA. Results. AMH was significantly decreased under treatment with 35 μg ethinylestradiol plus 2 mg cyproterone acetate (p = 0.002 at 3 months and p < 0.001 at 6 months). Treatment with 30 μg ethinylestradiol plus 3 mg drospirenone, and treatment with metformin 850 mg × 2 did not significantly affect serum AMH levels. AMH was significantly decreased under OCs treatment compared to metformin 850 mg × 2 (p = 0.005). Conclusion(s). AMH serum levels were significantly decreased under treatment with 35 μg ethinylestradiol plus 2 mg cyproterone acetate, due to decrease in androgens and suppression of gonadotropins.

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.