Objective To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. Methods In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). Results The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. Conclusion While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women. © 2013 International Menopause Society.

Objective: The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. Methods: This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima - media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Results: Women with the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46±1.74 vs. 8.60±1.51 m/s, P=0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Conclusion: Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Background Early treatment of breast cancer patients with loco-regional relapse or contralateral disease has been shown to improve survival. There is no current consensus on the optimal follow-up strategy. This study estimates the risk of isolated contralateral relapse (CR) after breast cancer surgery and its change over time, together with the efficacy of clinical examination, self-examination and mammography in the detection of CR. Methods Data from patients treated for early breast cancer at Guy's Hospital between 1990 and 1997 were collected and those with isolated contralateral recurrences were analysed. Life table analysis was performed and CR, CR-free and cumulative CR rates were calculated. Correlations were evaluated using Pearson's correlation coefficient. Results One thousand one hundred and forty-three women were included in the study and 23 patients had isolated CR. The median probability of CR was a constant 0.24% per year. Only one recurrence was found clinically at follow up, while the majority was detected through mammography and self-palpation. Conclusions The risk of CR is low and constant with time. Contralateral mammography is useful and can detect the vast majority of contralateral recurrences. These findings may have practical implications especially on the planning of postmastectomy follow up. Linked Comment: Fentiman. Int J Clin Pract 2013; 67: 1071-2. © 2013 John Wiley & Sons Ltd.

Vitamin D receptor's (VDR) genotypes have been associated both with the development of bone disease and the pathogenesis of multiple sclerosis (MS). We aimed to evaluate the association between the presence of Bsm1 restriction fragment length polymorphism of VDR and bone loss in ambulatory patients with MS. This cross-sectional study included 82 adult patients with relapsing-remitting MS. Fasting blood samples were obtained for biochemical-hormonal assessment and genotyping. Bone mineral density (BMD) was assessed at the lumbar spine (LS) and the femoral neck (FN), using dual energy X-ray absorptiometry. Possible associations between VDR's genotypes and BMD levels as well as biochemical and hormonal indices were evaluated. Among premenopausal women and men, carriers of the B allele exhibited higher BMD and Z score at the FN and a trend toward higher BMD at the LS, compared to patients with the bb genotype, after adjusting for age, BMI, sex, EDSS scoring, interferon administration, duration of MS and total steroids intake. Among postmenopausal women, the presence of the B allele was not associated with BMD or T score at any site, whereas carriers of the B allele exhibited higher levels of calcium (p value 0.008, univariate). No other significant differences were exhibited between levels of electrolytes, parathormone, 25-hydroxyvitamin D 3 and the genotype of VDR, in any of the groups. VDR's Bsm1 polymorphism is associated with a mild effect on BMD in younger patients with MS. Larger studies are necessary to corroborate these findings. © 2012 Springer-Verlag Italia.

We aimed to determine the second-trimester amniotic fluid (AF) levels of soluble Fas (sFas) and Fas-ligand (FasL) and investigate their association with fetal growth. Therefore, sFas and FasL levels were measured by enzyme immunoassay in the AF of 21 small for gestational age (SGA), 13 large for gestational age (LGA), and 44 appropriate for gestational age (AGA) fetuses of pregnant women who underwent amniocentesis at between 15 and 22 weeks gestation. Our study results showed that sFas and FasL levels were detectable in AF. sFAS median (25th-75th centile) levels were 3.8 (2.8-4.6). ng/ml in SGA, 3.6 (3.1-4.5). ng/ml in AGA, and 4.0 (3.1-4.4). ng/ml in LGA. FasL median (25th-75th centile) levels were 26.0 (20.3-32.7). pg/ml in SGA, 22.7 (18.4-28.5). pg/ml in AGA, and 21.5 (15.8-30.9). pg/ml in LGA. The differences were not statistically significant. Nevertheless, statistically significant differentiation of FasL levels existed when SGA fetuses in the extremes of distribution (≤5th, ≤2.5th centile) were considered. This is the first study presenting sFas and FasL concentrations in early second-trimester amniotic fluid in AGA, SGA, and LGA fetuses. We found indications that severe and very severe SGA fetuses (≤5th and ≤2.5th centile) have high levels of FasL in the amniotic fluid. This finding probably reflects the increased rate of apoptosis that is assumed to exist in cases of extreme growth restriction. © 2013 Elsevier Ireland Ltd.

Objective To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia. Study design In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy. Results In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p = 0.035) and in the 3rd trimester (202; 109-284) (p = 0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p = 0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%. Conclusions Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia. © 2013 Elsevier Ireland Ltd © 2013 Published by Elsevier Ireland Ltd. All rights reserved.

Aim: To assess the prevalence of climacteric symptoms and their association with demographic, life-style and hormonal parameters in Greek peri-and recently postmenopausal women. Methods: 1025 Greek women who were either perimenopausal or within their first 5 postmenopausal years participated in this cross-sectional observational study. Menopausal symptoms were assessed by the Greene Climacteric Scale and were tested for associations with demographic, anthropometric, life-style and hormonal parameters. Results: 29.8% Of the women reported moderate to severe menopausal symptoms. More specifically, 39.2% reported vasomotor, 21.3% psychological, 6.3% psychosomatic and 34.5% sexual symptoms. Years since menopause (r = 0.13, p < 0.01), waist circumference (r = 0.11, p < 0.05) as well as serum FSH, LH and estradiol (r = 0.15, r = 0.118, r =-0.157; p < 0.01) correlated with the intensity of menopausal symptoms. In the multivariate analysis years since menopause and serum estradiol were the only significant predictors of menopausal symptoms (b =-0.158 and b =-0.198, p < 0.001, respectively), explaining though only 4.8% of the variance. Conclusion: One out of three Greek women has moderate to severe climacteric symptoms during the menopause transition or the first postmenopausal years. This frequency is comparable to other White populations. Menopausal age and endogenous estrogens are significant predictors of climacteric symptoms. © 2013 Informa UK, Ltd.