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ABSTRACT: OBJECTIVE
To check the hypothesis that myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) onset in pregnant women with a family history of type 2 diabetes.RESEARCH DESIGN AND METHODSA 2-year, prospective, randomized, open-label, placebo-controlled study was carried out in pregnant outpatients with a parent with type 2 diabetes who were treated from the end of the first trimester with 2 g myo-inositol plus 200 µg folic acid twice a day (n = 110) and in the placebo group (n = 110), who were only treated with 200 µg folic acid twice a day. The main outcome measure was the incidence of GDM in both groups. Secondary outcome measures were as follows: the incidence of fetal macrosomia (>4,000 g), gestational hypertension, preterm delivery, caesarean section, shoulder dystocia, neonatal hypoglycemia, and neonatal distress respiratory syndrome. GDM diagnosis was performed according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) recommendations.RESULTSIncidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group: 6 vs. 15.3%, respectively (P = 0.04). In the myo-inositol group, a reduction of GDM risk occurrence was highlighted (odds ratio 0.35). A statistically significant reduction of fetal macrosomia in the myo-inositol group was also highlighted together with a significant reduction in mean fetal weight at delivery. In the other secondary outcome measures, there were no differences between groups.CONCLUSIONS myo-Inositol supplementation in pregnant women with a family history of type 2 diabetes may reduce GDM incidence and the delivery of macrosomia fetuses.
Diabetes care 01/2013; · 8.09 Impact Factor
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ABSTRACT: An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μ g molybdenum, 250 μ g boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β -glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (T max), concentration (C max), half-life (T 1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein T max (2 hrs), C max (0.7 μM), T 1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered T max (6 hrs), C max (0.57 μ M), T 1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption.
BioMed research international. 01/2013; 2013:273498.
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Herbert Marini,
Monica Currò,
Elena B Adamo,
Francesca Polito,
Nadia Ferlazzo,
Alessandra Bitto,
Marco Atteritano, Rosario D'Anna,
Angela Alibrandi,
Domenica Altavilla,
Francesco Squadrito,
Riccardo Ientile,
Daniela Caccamo
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ABSTRACT: The incidence of cardiovascular disease (CVD) and resultant morbidity and mortality are highly increased in postmenopausal women. Recent observations indicate the involvement of estrogen receptor beta in the pathogenesis of CVD, and the potential role of ESR2 gene polymorphisms as independent risk factors for CVD. We aimed to investigate the possible association between the ESR2 AluI 1730G>A gene polymorphism (rs4986938) with different CVD risk markers, such as body mass index (BMI), blood fibrinogen, glucose and insulin, homeostasis model assessment of insulin resistance and urinary F2-isoprostanes, in 89 postmenopausal women. Genotyping for ESR2 1730G>A polymorphism showed the higher prevalence of heterozygous GA1730 genotype than either wild-type GG1730 or homozygously mutated AA1730 genotype (50.6 vs 34.8 or 14.6%, respectively). Statistical analysis of between-group variability revealed that mean levels of the examined CVD risk markers, except BMI and fibrinogen, were within the normal range in all subjects grouped to different ESR2 1730G>A genotypes. Interestingly, only fibrinogen levels were statistically different in AA1730 carriers compared with other genotypes. The analysis of genotype relative risk showed a significant elevation of plasma fibrinogen in AA1730 carriers compared with GG+GA ones. The present data strongly indicate that genotyping for the ESR2 AluI 1730G>A gene variant should be included in a screening panel for assessment of cardiovascular risk in menopausal women.
Gene 08/2012; 508(2):206-10. · 2.34 Impact Factor
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Monica Currò,
Herbert Marini,
Angela Alibrandi,
Nadia Ferlazzo,
Salvatore Condello,
Francesca Polito,
Elena B Adamo,
Marco Atteritano, Rosario D'Anna,
Domenica Altavilla,
Alessandra Bitto,
Francesco Squadrito,
Riccardo Ientile,
Daniela Caccamo
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ABSTRACT: Multiple factors may contribute to the pathogenesis of postmenopausal osteoporosis including environmental, life-style and genetic factors. Common variants in ESR2 gene encoding for ER-beta, highly expressed in bone tissue, have recently been proposed as candidates for affecting bone phenotype at the population level, particularly in postmenopausal women. In this study, we examined the genetic background at ESR2 AluI (rs4986938, 1730G>A) locus in 89 osteopenic, postmenopausal women (age range 49-56 years) together with BMD at lumbar spine and femoral neck sites as well as variations in plasma levels of bone metabolism and turnover markers. Genotyping for ESR2 G1730A polymorphism showed that the frequency of A mutated allele accounted for 0.4 in our cohort of postmenopausal women; moreover, the GA1730 heterozygous individuals were the most represented (50.6%) compared with GG (37.8%) and AA homozygous ones (14.6%). A regression analysis showed that lumbar spine BMD values were significantly associated with both ESR2 AA1730 genotype (p=0.044) and time since the onset of menopause (p=0.031), while no significant association was detected between biochemical markers and genetic background. Interestingly, 85% of patients with AA1730 genotype presented the smallest lumbar spine BMD values. These findings first indicate a worsening effect of ESR2 AluI polymorphism on lumbar spine BMD reduction in postmenopause, suggesting that the detection of this ESR2 variant should be recommended in postmenopausal women, particularly in populations with a high prevalence of ESR2 AA1730 homozygous genotype.
The Journal of steroid biochemistry and molecular biology 06/2011; 127(3-5):413-7. · 2.66 Impact Factor
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ABSTRACT: The aim of this study was to evaluate whether myo-inositol, an insulin-sensitizing substance, may improve some features of metabolic syndrome in postmenopausal women.
Eighty postmenopausal women affected by the metabolic syndrome were enrolled prospectively in the study and treated with diet plus supplementation of myo-inositol (2 g BID plus diet: intervention group) or with diet plus placebo (control group) for 6 months. They were evaluated at baseline and after 6 months for insulin resistance (homeostasis model assessment ratio [HOMA] insulin resistance), lipid profile, and blood pressure.
Myo-inositol plus diet improved systolic and diastolic blood pressure, HOMA index, cholesterol, and triglyceride serum levels with highly significant differences, compared with the groups treated only with diet and placebo. In the group treated with myo-inositol, a decrease in diastolic blood pressure (-11%), HOMA index (-75%), and serum triglycerides (-20%) and an improvement in high-density lipoprotein cholesterol (22%) were shown.
Supplementation with myo-inositol may be considered a reliable option in the treatment of metabolic syndrome in postmenopausal women.
Menopause (New York, N.Y.) 01/2011; 18(1):102-4. · 3.08 Impact Factor
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Alessandra Bitto,
Roberta Granese,
Onofrio Triolo,
Daniela Villari,
Daniele Maisano,
Domenico Giordano,
Domenica Altavilla,
Herbert Marini,
Elena Bianca Adamo,
Piero Antonio Nicotina, Rosario D'Anna,
Francesco Squadrito
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ABSTRACT: Endometrial hyperplasia without cytological atypia is commonly treated with progestins, but other treatment regimes may be available with equivalent efficacy and low side effects.
A randomized double-blind, placebo and progesterone-controlled clinical trial to evaluate the effects of genistein aglycone in reducing endometrial hyperplasia.
A group of 56 premenopausal women with non-atypical endometrial hyperplasia were enrolled and received: genistein aglycone (n=19; 54 mg/day); norethisterone acetate (n=19; 10 mg/day on days 16-25 of the menstrual cycle) or placebo (n=18) for 6 months.
Hysteroscopy was performed with biopsies and symptomology assessed at baseline, 3 and 6 months of administration. The effect on estrogen (ER) and progesterone receptors (PR) expression in uterine biopsies were assessed after 3 and 6 months. For each treatment follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), sex hormone-binding globulin (SHBG) and progesterone (PG) levels were also evaluated.
After 6 months, 42% of genistein aglycone-administered subjects had a significant improvement of symptoms (histologically confirmed in the 29%) compared to 47% of norethisterone acetate subjects (histologically confirmed in the 31%), but only 12% in the placebo group with 19% exhibiting worsening symptoms and increased endometrial thickness. No significant differences were noted for hormone levels for any treatment, but immunohistochemical analysis revealed significantly reduced staining for ER-alpha and PR and enhanced ER-beta1 staining in genistein-administered subjects associated with a complete regression of bleeding.
These results suggest that genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women that cannot be treated with progestin.
Phytomedicine: international journal of phytotherapy and phytopharmacology 09/2010; 17(11):844-50. · 2.17 Impact Factor
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Clinical Chemistry 08/2010; 56(8):1355-7. · 7.91 Impact Factor
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Alessandra Bitto,
Francesca Polito,
Marco Atteritano,
Domenica Altavilla,
Susanna Mazzaferro,
Herbert Marini,
Elena Bianca Adamo, Rosario D'Anna,
Roberta Granese,
Francesco Corrado,
Silvia Russo,
Letteria Minutoli,
Francesco Squadrito
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ABSTRACT: Genistein aglycone positively affects postmenopausal symptoms. However, questions about its long-term safety on the thyroid gland still remain.
The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24 months. A subcohort (138 patients) continued therapy for an additional year.
Patients received ambulatory care.
Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67), plus calcium and vitamin D(3) at therapeutic doses. Circulating thyroid hormones (TSH, free T(3), free T(4)) and autoantibodies (thyroid peroxidase, thyroglobulin, and thyroid microsomal antigen) were assessed in 40 genistein and 37 placebo subjects who completed 3 yr. Thyroid hormone receptor (THRalpha and THRbeta) and retinoid receptor (RARalpha, RARgamma, and RXRalpha) expression from peripheral blood monocytes was also evaluated at baseline, 12, 24, and 36 months in all 3-yr completers.
Genistein administration over 3 yr did not affect serum thyroid hormones or autoantibodies. In addition, there were no differences in THRalpha, THRbeta, RARalpha, RARgamma, or RXRalpha mRNA expression between groups.
These data suggest that genistein aglycone intake does not significantly increase the risk of clinical or subclinical hypothyroidism at the dose of 54 mg/d.
The Journal of clinical endocrinology and metabolism 03/2010; 95(6):3067-72. · 6.50 Impact Factor
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ABSTRACT: Neutrophil gelatinase-associated lipocalin (NGAL) was evaluated prospectively through normal pregnancy and pregnancies complicated by preeclampsia syndrome. Sixty women enrolled in the study were evaluated for serum NGAL levels at 9-11 weeks gestation, at 24-26 weeks gestation and at delivery. Thirty women were affected by preeclampsia and 30 women with uncomplicated pregnancies formed the control group. NGAL serum concentrations in the preeclampsia group were higher compared to the control group, with significant differences in each trimester. In the first trimester, the median values were: 29.9 ng/mL [interquartile range (IQR) 24.1-50.1] versus 13.6 ng/mL (IQR 9.1-19.9; p < 0.001); in the second trimester: 59.6 ng/mL (IQR 25.3-82.6) versus 16.3 ng/mL (IQR 11.3-23.3; p < 0.001); and in the third trimester: 57.2 ng/mL (IQR 18.7-70.9) versus 15.8 ng/mL (IQR 9.1-22.5; p < 0.001). NGAL serum values were positively correlated with systolic and diastolic blood pressure and with proteinuria.
Acta Obstetricia Et Gynecologica Scandinavica 12/2009; 89(2):275-8. · 1.77 Impact Factor
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ABSTRACT: To evaluate which pregnant women with a single abnormal value in the oral glucose tolerance test are at increased risk for adverse perinatal outcome.
In this retrospective cohort study, we have evaluated the course of pregnancy in 152 consecutive women with only one abnormal value (OAV), and 624 with a 100 g - glucose tolerance test totally within the range values.
The prevalence of caesarean delivery, hypertensive disorders and macrosomia was higher in the study group when compared with the control group, whereas no difference was noted concerning gestational age at delivery, Apgar score at 1 and 5 min and neonatal hypoglycemia. Moreover, in the study group hypertensive disorders were more frequent in the subgroup with the elevated value at 1 h after the glucose load (25%), whereas macrosomia is more frequent when it is the fasting value to be elevated (29.7%).
Our results show that the implications of a single elevated glucose tolerance test value vary in relation to the timing of the abnormal value. In fact, OAV fasting or 1-h after load has a higher prevalence for an adverse obstetric outcome, whereas a 2 or 3-h value does not present significant differences when compared with the control group.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 07/2009; 22(7):597-601. · 1.36 Impact Factor
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Rosario D'Anna,
Maria Letizia Cannata,
Herbert Marini,
Marco Atteritano,
Francesco Cancellieri,
Francesco Corrado,
Onofrio Triolo,
Piero Rizzo,
Silvia Russo,
Agostino Gaudio,
Nicola Frisina,
Alessandra Bitto,
Francesca Polito,
Letteria Minutoli,
Domenica Altavilla,
Elena Bianca Adamo,
Francesco Squadrito
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ABSTRACT: To evaluate in a 24-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women, with no adverse effect on the endometrium and vagina.
A total of 389 participants met the parent study criteria and were randomly assigned to receive the phytoestrogen genistein (n = 198) or placebo (n = 191). About 40% of participants in both groups did not experience hot flushes, and the evaluation was performed in a subgroup of 236 participants (genistein, n = 119; placebo, n = 117). Reductions from the baseline in the frequency and severity of hot flushes were the principal criteria of efficacy. Endometrial thickness was evaluated by ultrasonography. The maturation value was also used to determine hormonal action on the vaginal cells.
There were no significant differences in vasomotor symptoms between groups at the baseline (4.4 +/- 0.33 hot flushes per day in the genistein group and 4.2 +/- 0.35 hot flushes per day in the control group). After 12 months of genistein therapy, there was a significant reduction (-56.4%) in the mean number of hot flushes, with a significant difference compared with the control group. After 24 months, there was no further decrease in the number of hot flushes in both groups. No significant difference was found in mean endometrial thickness and the maturation value score between the two groups, either at the baseline or after 24 months.
The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on the endometrium and vagina, but after the first year, there was no further improvement in the decrease in hot flushes.
Menopause (New York, N.Y.) 12/2008; 16(2):301-6. · 3.08 Impact Factor
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ABSTRACT: Neutrophil gelatinase-associated lipocalin (NGAL) concentrations, a product of neutrophils, were investigated in normal and preeclamptic pregnancies. Prospectively collected data and late second trimester (24-26 weeks) serum samples from 48 women who subsequently developed preeclampsia (PE) and 96 control women with uncomplicated pregnancies were compared. Serum NGAL values, as determined by quantitative sandwich enzyme immunoassay, were significantly increased in the preeclamptic compared to the control women: 76.9 ng/ml (interquartile range 39.7-96.5) versus 16.0 ng/ml (interquartile range 11.2-24.4) (p<0.001), and were positively correlated to blood pressure and proteinuria, showing a high sensitivity (75%) and specificity (94.5%). The results suggest that serum NGAL might be involved in the pathophysiology of PE and could be a marker for this syndrome.
Acta Obstetricia Et Gynecologica Scandinavica 10/2008; 87(12):1370-3. · 1.77 Impact Factor
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Herbert Marini,
Alessandra Bitto,
Domenica Altavilla,
Bruce P Burnett,
Francesca Polito,
Vincenzo Di Stefano,
Letteria Minutoli,
Marco Atteritano,
Robert M Levy, Rosario D'Anna, [......],
Francesco Cancellieri,
Maria Letizia Cannata,
Francesco Corrado,
Alessia Frisina,
Vincenzo Adamo,
Carla Lubrano,
Carlo Sansotta,
Rolando Marini,
Elena Bianca Adamo,
Francesco Squadrito
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ABSTRACT: Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain.
We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy.
The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Patients and Interventions: Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses.
Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers.
After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups.
After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women.
Journal of Clinical Endocrinology & Metabolism 10/2008; 93(12):4787-96. · 6.50 Impact Factor
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ABSTRACT: To evaluate the ability of endoglin, placental growth factor (PlGF) and the soluble form of vascular endothelial growth factor receptor (sFlt-1) measurements in gestational weeks 24-28 were used to predict pre-eclampsia.
Observational, prospective study. Setting. Department of Gynecological, Obstetrical Sciences and Reproductive Medicine, University of Messina. Sample. Fifty-two pre-eclamptic and 52 healthy pregnant women.
A maternal serum sample was frozen and stored at 1-h 50-g glucose challenge test between 24 and 28 weeks' gestation. A second maternal serum sample was collected at admission for the onset of the disease in the pre-eclamptic group and at admission for delivery in the control group. Levels of endoglin, sFlt-1 and the PlGF were measured in the stored serum. Pre-eclamptic subjects were also divided into women with early-onset (<37 weeks) and women with late-onset pre-eclampsia (> or =37 weeks).
Levels of endoglin, sFlt-1, and sFlt-1:PlGF ratio were found to be higher in the pre-eclamptic group in both trimesters. No differences were found between early- and late-onset pre-eclamptic. The Receiver Operating Characteristics curve, applied to the second trimester marker values, showed the best diagnostic profile for sFlt-1:PlGF (area under the curve, AUC=0.92) followed by endoglin (AUC=0.88), sFlt-1 (AUC=0.87) and PlGF (AUC=0.83). This finding was confirmed by Bayesian analysis which highlighted a specificity, a sensitivity, a diagnostic accuracy, a positive predictive value and a negative predictive value of 88.5% for sFlt-1:PlGF using a cut-off of 38.47.
Endoglin, PlGF and sFlt-1 might be used as markers for predicting pre-eclampsia, but sFlt-1:PlGF seems to be more accurate.
Acta Obstetricia Et Gynecologica Scandinavica 07/2008; 87(8):837-42. · 1.77 Impact Factor
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Marco Atteritano,
Francesco Pernice,
Susanna Mazzaferro,
Stefania Mantuano,
Alessia Frisina, Rosario D'Anna,
Maria Letizia Cannata,
Alessandra Bitto,
Francesco Squadrito,
Nicola Frisina,
Michele Buemi
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ABSTRACT: To evaluate in a twelve-month, randomized placebo-controlled study whether pure administration of phytoestrogen genistein (54 mg/day) might reduce cytogenetic biomarkers in peripheral lymphocytes of postmenopausal women. A total of 57 postmenopausal women met the criteria and were randomly assigned to receive phytoestrogen genistein (n = 30) or placebo (n = 27). There was no significant difference in age, length of time since menopause or body mass index between the two groups. After one year, plasma genistein level was 0.14 +/- 0.01 micromol/L in the control group and 0.72 +/- 0.08 micromol/L in the genistein group (P < 0.0001). At baseline, sister chromatid exchange rate was 4.97 +/- 2.17 in the control group and 4.96 +/- 1.83 in the genistein group (P = 0.89). After one year, sister chromatid exchange rate was 4.96 +/- 2.16 in the control group and 3.98 +/- 1.14 in the genistein group (P < 0.05). High frequency cells count was 3% in the genistein group and 5% in the control group (P < 0.05) at the end of the study. Chromosomal aberration frequency was 5.55% in the control group at time 0 and 5.75% in the genistein group; after one year, the figures were 5.86% in the control group and 4.5% in the genistein group (P < 0.05). After one year, there was a negative relationship between sister chromatid exchange rate and plasma levels (r = - 0.43; P < 0.05) in the genistein group. Phytoestrogen genistein has been shown in postmenopausal women to be effective in the reduction of cytogenetic biomarkers. The protective effect on genomic damage appears to be a particularly promising tool in reducing the risk of cancer.
European Journal of Pharmacology 06/2008; 589(1-3):22-6. · 2.52 Impact Factor
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Herbert Marini,
Letteria Minutoli,
Francesca Polito,
Alessandra Bitto,
Domenica Altavilla,
Marco Atteritano,
Agostino Gaudio,
Susanna Mazzaferro,
Alessia Frisina,
Nicola Frisina, [......],
Michele Bonaiuto, Rosario D'Anna,
Maria Letizia Cannata,
Francesco Corrado,
Francesco Cancellieri,
Marianna Faraci,
Rolando Marini,
Elena Bianca Adamo,
Steven Wilson,
Francesco Squadrito
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ABSTRACT: RANKL and its decoy receptor osteoprotegerin (OPG) constitute a complex physiological mediator system involved in the regulation of bone resorption and may be responsible for the homeostatic mechanism of normal bone remodeling. Genistein, an isoflavone representing 1-5% of total phytoestrogen content in soybean products, may positively regulate cellular bone metabolism, but its mechanism of action on bone is not yet fully understood.
We studied the serum levels of both soluble RANKL (sRANKL) and OPG and the sRANKL/OPG ratio in 389 postmenopausal women (age, 49-67 yr) with a femoral neck BMD <0.795 g/cm(2) and no significant comorbid conditions after 24-mo therapy with genistein, (n = 198; 54 mg/d) or placebo (n = 191). Both intervention and placebo contained calcium and vitamin D(3). All patients received dietary instruction in an isocaloric fat-reduced diet.
In comparison with placebo, sRANKL level was lower (p < 0.001 versus placebo) and OPG higher in genistein recipients (p < 0.001 versus placebo) at 1 and 2 yr, respectively. Moreover, at the end of 24 mo, genistein produced a significant reduction in the sRANKL/OPG ratio compared with placebo (genistein = -0.021, 95% CI, -0.020 to -0.022; placebo = +0.004, 95% CI, 0.003-0.005; difference = -0.020, 95% CI, -0.015 to -0.025, p < 0.001).
Our findings suggest that genistein plus calcium and vitamin D(3) as part of a healthy diet is able to positively modulate bone turnover in a cohort of osteopenic, postmenopausal women and improve sRANKL-OPG balance after 24 mo of treatment.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2008; 23(5):715-20. · 6.04 Impact Factor
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Herbert Marini,
Letteria Minutoli,
Francesca Polito,
Alessandra Bitto,
Domenica Altavilla,
Marco Atteritano,
Agostino Gaudio,
Susanna Mazzaferro,
Alessia Frisina,
Nicola Frisina, [......],
Michele Bonaiuto, Rosario D'Anna,
Maria Letizia Cannata,
Francesco Corrado,
Francesco Cancellieri,
Marianna Faraci,
Rolando Marini,
Elena Bianca Adamo,
Steven Wilson,
Francesco Squadrito MD
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ABSTRACT: Introduction: RANKL and its decoy receptor osteoprotegerin (OPG) constitute a complex physiological mediator system involved in the regulation of bone resorption and may be responsible for the homeostatic mechanism of normal bone remodeling. Genistein, an isoflavone representing 1–5% of total phytoestrogen content in soybean products, may positively regulate cellular bone metabolism, but its mechanism of action on bone is not yet fully understood.Materials and Methods: We studied the serum levels of both soluble RANKL (sRANKL) and OPG and the sRANKL/OPG ratio in 389 postmenopausal women (age, 49–67 yr) with a femoral neck BMD <0.795 g/cm2 and no significant comorbid conditions after 24-mo therapy with genistein, (n = 198; 54 mg/d) or placebo (n = 191). Both intervention and placebo contained calcium and vitamin D3. All patients received dietary instruction in an isocaloric fat-reduced diet.Results: In comparison with placebo, sRANKL level was lower (p < 0.001 versus placebo) and OPG higher in genistein recipients (p < 0.001 versus placebo) at 1 and 2 yr, respectively. Moreover, at the end of 24 mo, genistein produced a significant reduction in the sRANKL/OPG ratio compared with placebo (genistein = −0.021, 95% CI, −0.020 to −0.022; placebo = +0.004, 95% CI, 0.003–0.005; difference = −0.020, 95% CI, −0.015 to −0.025, p < 0.001).Conclusions: Our findings suggest that genistein plus calcium and vitamin D3 as part of a healthy diet is able to positively modulate bone turnover in a cohort of osteopenic, postmenopausal women and improve sRANKL-OPG balance after 24 mo of treatment.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2008; 23(5):715 - 720. · 6.04 Impact Factor
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ABSTRACT: To present the results obtained in 104 cases of vaginal aplasia resolved with self-dilatation or with surgical procedures such as the McIndoe or Williams operations.
Retrospective study.
Departments of obstetrics and gynecology of universities in Bologna, Modena, and Messina, Italy.
One hundred four cases of vaginal aplasia.
Self-dilatation and surgical procedures such as the McIndoe or Williams operations.
Outcome of the treatment.
From 1977 to 2002, 104 cases of vaginal agenesis were treated. The mean age of the treated patients was 16.5 years old (range, 13-18 years). After 6 months of self-dilatation, 41 subjects obtained a new cavity of about 10-12 cm in length. In 14 patients, a space ranging from 3 to 5 cm was obtained. The technique failed in 49 patients. Fourteen patients underwent the Williams surgical procedure, while the remaining 49 patients underwent to the McIndoe procedure. All patients were successfully treated, and the only complication, a rectovaginal fistula that was repaired, occurred in one case of the McIndoe operation.
Self-dilatation should be the first approach because of its high success rate; the Williams surgical approach should be chosen when self-dilatation partially fails or when previous surgical attempts are unsuccessful. Finally, the McIndoe procedure and its variants should be used when self-dilatation completely fails.
Fertility and sterility 01/2008; 88(6):1653-6. · 3.97 Impact Factor
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Marco Atteritano,
Herbert Marini,
Letteria Minutoli,
Francesca Polito,
Alessandra Bitto,
Domenica Altavilla,
Susanna Mazzaferro, Rosario D'Anna,
Maria Letizia Cannata,
Agostino Gaudio,
Alessia Frisina,
Nicola Frisina,
Francesco Corrado,
Francesco Cancellieri,
Carla Lubrano,
Michele Bonaiuto,
Elena Bianca Adamo,
Francesco Squadrito
[show abstract]
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ABSTRACT: Genistein, a soy isoflavone, has received wide attention over the last few years because of its potential preventive role for cardiovascular disease.
Our objective was to assess the effects of genistein administration (54 mg/d) on some predictors of cardiovascular risk in osteopenic, postmenopausal women.
We conducted a randomized, double-blind, placebo-controlled trial at three Italian university medical centers.
After a 4-wk stabilization on a standard isocaloric, fat-reduced diet, participants were randomly assigned to receive genistein (n = 198) or placebo (n = 191) daily for 24 months. Both intervention and placebo contained calcium and vitamin D(3).
Blood lipid profiles, fasting glucose and insulin, homeostasis model assessment for insulin resistance, fibrinogen, soluble intercellular adhesion molecule-1, soluble vascular cellular adhesion molecule-1, F2-isoprostanes, and osteoprotegerin at baseline and after 12 and 24 months of treatment were measured.
Compared with placebo, genistein significantly reduced fasting glucose and insulin as well as homeostasis model assessment for insulin resistance after both 12 and 24 months of treatment. By contrast, genistein administration did not affect blood lipid levels although fibrinogen, F2-isoprostanes, soluble intercellular adhesion molecule-1, and soluble vascular cellular adhesion molecule-1 decreased significantly compared with placebo after 24 months. Serum osteoprotegerin was higher in the genistein group compared with placebo. At 24 months, the genistein group showed no change in endometrial thickness compared with placebo. Most treatment-related adverse events were moderate and composed of gastrointestinal side effects [genistein, n = 37 (19%); placebo, n = 15 (8%)].
These results suggest that 54 mg genistein plus calcium, vitamin D(3), and a healthy diet was associated with favorable effects on both glycemic control and some cardiovascular risk markers in a cohort of osteopenic, postmenopausal women.
Journal of Clinical Endocrinology & Metabolism 09/2007; 92(8):3068-75. · 6.50 Impact Factor
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Herbert Marini,
Letteria Minutoli,
Francesca Polito,
Alessandra Bitto,
Domenica Altavilla,
Marco Atteritano,
Agostino Gaudio,
Susanna Mazzaferro,
Alessia Frisina,
Nicola Frisina,
Carla Lubrano,
Michele Bonaiuto, Rosario D'Anna,
Maria Letizia Cannata,
Francesco Corrado,
Elena Bianca Adamo,
Steven Wilson,
Francesco Squadrito
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ABSTRACT: Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive.
To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women.
Randomized, double-blind, placebo-controlled trial.
3 university medical centers in Italy.
389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions.
After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D.
The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected.
At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. -0.053 g/cm2 [CI, -0.058 to -0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P < 0.001) and the femoral neck (change, 0.035 g/cm2 [CI, 0.025 to 0.042] vs. -0.037 g/cm2 [CI, -0.044 to -0.027]; difference, 0.062 g/cm2 [CI, 0.049 to 0.073]; P < 0.001). Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P = 0.002) and discontinued the study. Limitations: The study did not measure fractures and had limited power to evaluate adverse effects.
Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.
Annals of internal medicine 07/2007; 146(12):839-47. · 16.73 Impact Factor
