Alexandros D. Saltamavros

Basal metabolic rate is decreased in women with polycystic ovary syndrome and biochemical hyperandrogenemia and is associated with insulin resistance.

OBJECTIVEnTo evaluate basal metabolic rate (BMR) in women with PCOS and to determine its association with insulin resistance (IR).nnnDESIGNnProspective assessment of BMR in women with PCOS.nnnSETTINGnOutpatient clinic of the Division of Reproductive Endocrinology.nnnPATIENT(S)nThe study included 91 Greek women with PCOS and biochemical hyperandrogenemia, with mean age 24.03 +/- 0.55 years and mean body mass index (BMI) 26.67 +/- 0.69 kg/m(2), and 48 matched regularly menstruating women, with mean age 26.33 +/- 0.93 years and mean BMI 23.35 +/- 0.85 kg/m(2), as control subjects.nnnINTERVENTION(S)nAssessment of BMR by indirect calorimetry, IR by HOMA and QUICKI indices, fasting insulin, and fasting glucose/insulin ratio.nnnMAIN OUTCOME MEASURE(S)nReduced BMR in PCOS with or without IR.nnnRESULT(S)nAdjusted BMR was 1,868 +/- 41 kcal/day in the control group, 1,445.57 +/- 76 in all PCOS women, 1,590 +/- 130 in PCOS women without IR and 1,116 +/- 106 in PCOS women with IR. Adjusted BMR showed a statistically significant difference between women with PCOS and control subjects, with lowest values in the group of PCOS women with IR, even after adjusting all groups for age and BMI.nnnCONCLUSION(S)nWomen with PCOS, particularly those with IR, present a significantly decreased BMR.

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

Objective.u2003To 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.u2003Prospective randomised study. Setting. Division of Endocrinology and Human Reproduction, Aristotle University of Thessaloniki. Patients.u2003Forty-five (45) women with PCOS diagnosed according to the criteria proposed in 1990 by the NIH. Interventions.u2003Women with PCOS were randomised into three groups, all treated for 6 months: Group A received an OC containing 35u2009μg ethinylestradiol plus 2u2009mg cyproterone acetate, Group B received an OC containing 30u2009μg ethinylestradiol plus 3u2009mg drospirenone and Group C received metformin 850u2009mgu2009×u20092. Main outcome measure(s).u2003Anti-Müllerian hormone levels were measured by a specific ELISA. Results.u2003AMH was significantly decreased under treatment with 35u2009μg ethinylestradiol plus 2u2009mg cyproterone acetate (pu2009=u20090.002 at 3 months and pu2009<u20090.001 at 6 months). Treatment with 30u2009μg ethinylestradiol plus 3u2009mg drospirenone, and treatment with metformin 850u2009mgu2009×u20092 did not significantly affect serum AMH levels. AMH was significantly decreased under OCs treatment compared to metformin 850u2009mgu2009×u20092 (pu2009=u20090.005). Conclusion(s).u2003AMH serum levels were significantly decreased under treatment with 35u2009μg ethinylestradiol plus 2u2009mg cyproterone acetate, due to decrease in androgens and suppression of gonadotropins.

Decreased active, total and altered active to total ghrelin ratio in normal weight women with the more severe form of polycystic ovary syndrome

OBJECTIVEnTo assess total, active and active to total serum ghrelin ratio in normal weight women with polycystic ovary syndrome (PCOS) and in healthy ovulatory control women.nnnSTUDY DESIGNnThe study included 50 normal weight women with PCOS with a mean age of 23.70+/-4.99 years and 10 control women with a mean age of 30+/-5.80 years. The diagnosis of PCOS was based on the presence of biochemical hyperandrogenemia, chronic anovulation and polycystic ovarian morphology according to the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Serum total and active ghrelin were measured by RIA, using commercially available kits.nnnRESULTSnA significantly lower serum active/total ghrelin ratio was noted in the more severe form of PCOS with hyperandrogenemia, chronic anovulation and polycystic ovarian morphology. Both total and active serum ghrelin levels were negatively correlated to hirsutism score, to plasma glucose levels and to QUICKI and HOMA-IR indices of Insulin Resistance. A statistically significant difference was detected between the more severe and the milder forms of PCOS, concerning serum levels of total ghrelin (p=0.017), active ghrelin (p=0.007) and the active/total ghrelin ratio (p=0.026).nnnCONCLUSIONSnThe results of the present study demonstrate an altered active to total ghrelin ratio, as well as a tendency towards lower both total and active fasting serum ghrelin levels in normal weight PCOS, more pronounced in the more severe forms of the syndrome.

Association of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor γ2 with decreased basic metabolic rate in women with polycystic ovary syndrome

OBJECTIVEnThe peroxisome proliferator-activated receptor (PPAR)gamma is a transcription factor involved in glucose homeostasis and energy metabolism. A missense mutation at codon 12 in the PPARgamma2 has been associated with increased body mass index (BMI) and attenuated insulin resistance (IR) in polycystic ovary syndrome (PCOS). We have recently shown a decreased basic metabolic rate (BMR) in PCOS. The aim of the present study is to determine the prevalence of the Pro12Ala polymorphism of the PPARgamma2 gene and its associations with indices of IR and BMR in lean and slightly overweight PCOS women.nnnDESIGNnCase-control association study involving 156 PCOS women with biochemical hyperandrogenism, chronic anovulation and polycystic ovarian morphology in ultrasound and 56 unrelated healthy controls.nnnMETHODSnHormonal determinations were performed by electrochemiluminescence quantitation or RIA. BMR was measured by indirect calorimetry. All subjects were genotyped by a PCR-restriction fragment length polymorphism assay.nnnRESULTSnGenotype frequencies of the Pro12Ala polymorphism in PPARgamma2 did not differ among PCOS women and control subjects. The presence of Pro12Ala polymorphism of PPARgamma2 was associated with lower BMR (P=0.04). This finding was valid in our subgroup of lean PCOS (BMI<25 kg/m(2)), in which the Ala variant was also associated with higher total testosterone values.nnnCONCLUSIONnThe Pro12Ala polymorphism in the PPARgamma2 gene is associated with decreased BMR in women with PCOS and biochemical hyperandrogenemia. These young women are therefore at risk to increase their body weight and should restrict their energy intake by diet and enhance their energy expenditure by exercise.

Association of the 17-hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) with hyperandrogenemia in polycystic ovary syndrome (PCOS)

OBJECTIVEnTo evaluate the association of an activating single-nucleotide polymorphism (SNP) at position -71 of the promoter of 17beta-hydroxysteroid dehydrogenase type 5 gene (-71A/G HSD17B5 SNP) and polycystic ovary syndrome (PCOS) in a well characterized cohort of caucasian PCOS women with biochemical hyperandrogenemia.nnnDESIGNnThe PCOS patients and unrelated healthy control subjects were genotyped for the -71A/G HSD17B5 SNP. The acquired genotypic data was tested for association with PCOS and other quantitative phenotypic traits of the syndrome in PCOS patients.nnnSETTINGnSubjects were recruited from the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, at the University Hospital of Patras, Greece. Genotyping and biochemical determinations took place at the Laboratory of Molecular Endrocinology, University of Patras Medical School, Rion, Greece.nnnPATIENT(S)nParticipants comprised 150 caucasian Greek PCOS women with biochemical hyperandrogenism and chronic anovulation and polycystic ovarian morphology on ultrasound and 51 healthy control subjects.nnnMAIN OUTCOME MEASURE(S)nHSD17B5 genotype, serum testosterone, serum androstenedione.nnnRESULT(S)nNo association of the -71A/G HSD17B5 SNP with PCOS was detected. However, the -71G HSD17B5 variant was associated with increased serum testosterone levels and decreased androstenedione/testosterone ratio.nnnCONCLUSION(S)nThe -71G HSD17B5 variant is not a major component of the molecular pathogenetic mechanisms of PCOS, although it might contribute to the severity of hyperandrogenemia in women with PCOS and biochemical hyperandrogenism.

Obesity and insulin resistance increase plasma viscosity in young women with polycystic ovary syndrome

Objective.u2003To investigate the plasma viscosity in young women with polycystic ovary syndrome (PCOS). Design.u2003Patients with PCOS and healthy controls were assessed for plasma viscosity. The acquired data were tested for association with hyperandrogenemia, obesity and insulin resistance (IR) in patients with PCOS. Plasma viscosity was determined by a viscometer Type 53610/I SCHOTT-Instruments, Mainz at 37°C. Patients.u2003The study included 96 young women with PCOS and 72 healthy controls. Main outcome measures.u2003Plasma viscosity and IR. Results.u2003Plasma viscosity was 1.243 ± 0.67 mm2/s in the control group and 1.252 ± 0.82 in women with PCOS (p = 0.416). Using multiple regression analysis, total protein (B = 0.348, p = 0.005), area under curve for insulin (B = 0.320, p = 0.011) and BMI (B = 0.315, p = 0.013) were proven to be significantly correlated to plasma viscosity. Plasma viscosity was significantly increased in women with PCOS with IR compared to matched for age and BMI PCOS women without IR (1.300 ± 0.055 vs. 1.231 ± 0.049 mm2/s) (p = 0.004). Conclusion.u2003Young women with PCOS presented a plasma viscosity that was increased by obesity and IR. Therefore, clinical management of young overweight women with PCOS with IR should always include a serious reduction in body weight and the use of oral contraceptive treatment with cautious.

Estrogen receptor polymorphisms in tamoxifen-treated women with breast cancer

In postmenopausal women with estrogen receptor (ER)-positive breast cancer, long-term tamoxifen administration has proved beneficial after surgical treatment and subsequent chemotherapy. One of the major adverse effects of tamoxifen is the development of endometrial pathology (polyps, endometrial hyperplasia and endometrial cancer). PvuII and XbaI polymorphisms of the estrogen receptor-α gene (ERα) and RsaI and AluI polymorphisms of the estrogen receptor-β gene (ERβ) have been associated with breast cancer. Thus the present study aimed to identify whether ER gene polymorphisms are associated with breast cancer stage or endometrial responsiveness to long-term tamoxifen treatment in 87 postmenopausal, tamoxifen-treated women with ER-positive breast cancer. The mean age of the patients was 58.7 ± 4.7 years and the mean duration of tamoxifen treatment was 3.9 ± 1.1 years. At diagnosis, the stage of breast cancer was determined as follows: 29 women (32%) at Stage I, 49 (58%) at Stage II and 9 (10%) at Stage III. The frequency distributions of the estrogen receptor polymorphisms in all women with breast cancer were not different from those predicted by the Hardy-Weinberg equilibrium hypothesis (p > 0.10). None of the ER polymorphisms studied was linked to either the presence of endometrial pathology or the stage of breast cancer.

No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia

PurposeThe aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance.MethodsThe study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR–restriction fragment length polymorphism (RLFP) assay.ResultsNo association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected.ConclusionThe G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.

The influence of obesity on Androstenedione to Testosterone ratio in women with polycystic ovary syndrome (PCOS) and hyperandrogenemia

The aim of the present study was to evaluate the impact of obesity and insulin resistance on testosterone formation from androstenedione and its contribution to biochemical hyperandrogenemia in all different phenotypic subgroups of PCOS patients. The case-control study included 1087 PCOS women and 206 regularly menstruating, ovulatory controls. The main clinical measurements included anthropometric and basal hormonal characteristics and evaluation of hyperandrogenic and insulin resistance-related features. The results were the following: In PCOS women with biochemical hyperandrogenemia, obesity significantly lowers serum A levels and increases T to A ratio. These findings were not present in PCOS women with clinical hypeandrogenemia and in normal ovulatory controls.

Increased plasma viscosity in young women with polycystic ovary syndrome using an oral contraceptive containing 35 μg ethinyl estradiol and 2 mg cyproterone acetate.

Objectives.u2003To investigate the influence of 6 months of treatment with an oral contraceptive (OC) containing 35u2009μg ethinyl estradiol and 2 mg cyproterone acetate on plasma viscosity (PV) in young women with polycystic ovary syndrome (PCOS). Design.u2003Patients with PCOS were assessed for PV before and after 6 months of treatment with an OC containing 35u2009μg ethinyl estradiol and 2 mg cyproterone acetate. PV was determined by a viscometer Type 53610/I SCHOTT-Instruments, Mainz at 37°C. Settings.u2003Subjects were recruited from the Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology at the University Hospital of Patras, Greece. Patients.u2003The study included 66 young women with PCOS. Main outcome measures.u2003PV. Results.u2003In PCOS women as a whole, PV at baseline was 1.249u200a±u200a0.049 mm2/s (nu200a=u200a66). After 6 months of treatment with an OC containing 35u2009μg ethinyl estradiol and 2 mg cyproterone acetate, PV was increased to 1.268u200au200a±u200au200a0.065 mm2/s (pu200a=u200a0.038). The difference between PV before and after 6 months of treatment with an OC containing 35u2009μg ethinyl estradiol and 2 mg cyproterone acetate (Δviscosity) was 0.01864u200au200a±u200au200a0.071452 mm2/s. ΔViscosity was related to Δfibrinogen (ru200a=u200a0.270, pu200a=u200a0.046), to Δhematocrit (ru200a=u200a0.514, pu200a=u200a0.09) and to Δtriglycerides (ru200a=u200a0.292, pu200a=u200a0.021). Conclusion.u2003Young women with PCOS presented an increased PV under OC treatment with 35u2009μg ethinyl estradiol and 2 mg cyproterone acetate.