The differential effect of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women: relationship with the metabolic status.

CONTEXT: The wide family of the phytoestrogens has become an alternative to the classical hormonal therapy in menopause; nevertheless, some findings are still conflicting. OBJECTIVE: To examine the effect of genistein administration on metabolic parameters and vascular reactivity considering the basal endocrine status of the patients. DESIGN AND SETTING: A randomized placebo controlled study was conducted at a university hospital. PARTICIPANTS: Fifty postmenopausal women participated. INTERVENTIONS: Thirty subjects (group A) were randomized to receive 54 mg/d genistein while 20 subjects (group B) were treated with the placebo for 24 wk. In group A, we distinguish two subgroups: 14 normoinsulinemic and 12 hyperinsulinemic patients. MAIN OUTCOME MEASURES: Anthropometric measures, hormonal and lipid assays, oral glucose tolerance test with glycemic, insulin, and C-peptide evaluation, indexes of insulin sensitivity and endothelial function, and euglycemic-hyperinsulinemic clamps were performed. RESULTS: The insulin basal values significantly decreased in group A, whereas the homeostasis model index of insulin sensitivity and the fasting glucose levels significantly improved compared with placebo group. The genistein administration decreased fasting glucose and area under the curve glucose levels in the normoinsulinemic patients after treatment. In the hyperinsulinemic patients, a significant reduction in fasting insulin, fasting C-peptide, and area under the curve insulin levels as well as an increase in fractional hepatic insulin extraction was shown. In these patients, high-density lipoprotein cholesterol levels were significantly improved. The endothelium-dependent and -independent dilatation improved in the treated group. Normoinsulinemic patients showed both a significantly enhanced flow-mediated and nitrate-mediated dilatation, whereas no significant changes were found in the hyperinsulinemic group. CONCLUSIONS: The glycoinsulinemic metabolism and the endothelial function were significantly influenced by genistein. In particular, normoinsulinemic patients showed an improvement in glycemic and vascular reactivity indexes. Conversely, an improvement in the insulin sensitivity indexes was noted in hyperinsulinemic patients.

Fasting and post-methionine homocysteine levels in Alzheimers disease and vascular dementia.

The aim of the study is to compare the basal homocysteine levels in patients with impairment of cognitive status, and in controls, to evaluate if the methionine loading test is able to identify any differences between patients with Alzheimers disease and patients with vascular dementia. We enrolled 56 subjects, 20 with Alzheimers disease, 18 with vascular dementia, and 18 normal controls. The data shown that plasma homocysteine levels both basal and post-methionine load were significantly higher in the two groups of demented patients than in the control group. No significant differences were found between Alzheimers patients and vascular dementia patients. The homocysteine percent increase after a methionine loading test was significantly higher in the controls with respect to the two groups of demented patients. Only in Alzheimers patients were vitamin B(12) basal levels negatively correlated with basal homocysteine levels (p<0.05), while positively correlated with the homocysteine percent increase after load (p<0.05). The study confirms the possible role of chronically elevated homocysteinemia in neuronal degeneration in demented patients. Even if the methionine loading test revealed an abnormal homocysteine metabolism in demented patients, it didnt show any difference among patients with Alzheimers disease and vascular dementia.

L-folic acid supplementation in healthy postmenopausal women: effect on homocysteine and glycolipid metabolism.

CONTEXT: Hyperhomocysteinemia as well as alterations of glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases. OBJECTIVE: The aim of this study was to examine the effect of L-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women. DESIGN: This study was a randomized placebo, not double-blind, trial. SETTING: The study was performed in an academic research center. PATIENTS OR OTHER PARTICIPANTS: Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect lipid or glucose metabolism. INTERVENTION(S): Patients underwent two hospitalizations before and after 8 wk of L-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Hcy metabolism was studied by a standardized oral methionine-loading test. MAIN OUTCOME MEASURE(S): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured. RESULTS: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P < 0.01) in L-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P < 0.02). Furthermore, L-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P < 0.05) and peripheral insulin sensitivity (P < 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (P < 0.03). CONCLUSIONS: These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.

Oocyte donation programs: strategy for improving results.

Oocyte donation is now a useful option for women who cannot start a spontaneous pregnancy for reasons related to advanced age, iatrogenic factors, early depletion of ovarian reserve, or genetic disorders. Embryo implantation rates, pregnancy rates, and pregnancy outcomes among women included in oocyte donation programs were shown to be comparable to those of spontaneous or in vitro fertilization (IVF) pregnancies. With oocyte freezing and cryobanks, recipients may have a successful response to oocyte donation, with no need to be on waiting lists, access to a larger number of oocytes from the same donor, and a lesser risk of infectious disease transmission.

Low-dose estrogen and drospirenone combination: effects on glycoinsulinemic metabolism and other cardiovascular risk factors in healthy postmenopausal women.

OBJECTIVE: To evaluate the effects of a daily E2 (1 mg) plus drospirenone oral formulation (2 mg) on glycoinsulinemic metabolism, lipid profile, and endothelial function in symptomatic healthy menopausal women. DESIGN: Randomized, double-blind study. SETTING: Operative Division of Endocrinological Gynecology, Catholic University of the Sacred Heart, Rome, Italy. PATIENT(S): Forty postmenopausal women. INTERVENTION(S): Patients were randomly submitted to receive treatment with an oral dose of E2 (1 mg) plus drospirenone (2 mg) (group A) or placebo (group B). MAIN OUTCOME MEASURE(S): Hormonal and lipid assessment; evaluation of glucose and insulin metabolism by the clamp test and the oral glucose tolerance test; evaluation of endothelial function by the vascular reactivity test. RESULT(S): Total cholesterol levels, low-density lipoprotein cholesterol levels, and nonesterified fatty acids levels significantly decreased both after 3 and 6 months. No changes in high-density lipoprotein, triglycerides, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) were found. Treatment resulted in few changes in glycoinsulinemic metabolism. We observed a significant reduction of the area under curve of insulin after 6 months of therapy. Endothelial function was significantly influenced by treatment, and an improvement in both flow-mediated dilatation and nitrate-mediated dilatation values after 6 months was observed. CONCLUSION(S): Low-dose E2/drospirenone treatment did not reveal any negative effect on carbohydrate metabolism, acting in a neutral way on insulin sensitivity. The treatment induced favorable changes in lipid profile and showed a significant improvement of vascular reactivity.

Estro-progestin supplementation enhances the growth hormone secretory responsiveness to ghrelin infusion in postmenopausal women.

OBJECTIVE: To assess the effects of estro-progestin supplementation on ghrelin-mediated GH release, we studied the consequence of ghrelin or saline injection before and after 60 days of hormone therapy or placebo administration in postmenopausal subjects. DESIGN: A prospective double blind, placebo-controlled, and parallel cohort study. SETTING: Catholic University of Sacred Heart, Operative Division of Endocrinological Gynecology. PATIENT(S): Eighteen postmenopausal women participated in the study. INTERVENTION(S): Ten women were randomized to receive estro-progestin treatment (2 mg of hemihydrate E(2) and 10 mg of dydrogesterone in a continuous sequential regimen); eight women were treated with placebo. All patients underwent in a randomized order a ghrelin test (1 microg/kg IV bolus) or a saline infusion (2-mL IV bolus) on two different days, before and after 60 days of treatment. MAIN OUTCOME MEASURE(S): Basal hormonal assays, including ghrelin basal levels. The GH levels were measured at baseline and after 15, 30, 60, 90 minutes of ghrelin or saline injection. RESULT(S): The acute ghrelin injection released a notable GH secretion in all postmenopausal women. After estro-progestin therapy the ghrelin-stimulated GH response was significantly higher than before treatment. In particular, the percent increase of ghrelin GH-releasing effect, expressed as incremental area under the curve (AUCi-GH) was more than 50% after hormone therapy. CONCLUSION(S): In postmenopausal women estro-progestin treatment clearly influenced the ghrelin-stimulated GH secretion.

Hyperhomocysteinemia and cardiovascular risk in postmenopausal women: the role of folate supplementation.

In the postmenopausal period, cardiovascular diseases are a frequent chronic condition leading to high risk of myocardial infarction and death. Recently hyperhomocysteinemia and even mildly elevated plasma concentrations of homocysteine have been recognized as independent risk factors for vascular damage predisposing to arteriosclerosis. Elevated plasma levels of homocysteine induce vascular endothelial damage and are frequently associated with low folate levels. In this review we evaluate literature data on some aspects related to menopause and homocysteine metabolism. In particular, we show the effect of folic acid supplementation on homocysteine concentrations and on homocysteine-related thiols, such as cysteine and cysteine-glycine, as well as the relationship with glucose, insulin, and lipidic metabolism in postmenopausal women. We also analyze the influence of folate supplementation on endothelial function, by brachial artery flow-mediated dilatation (endothelium-dependent) and nitroglycerine-induced dilatation (endothelium-independent) before and after a methionine load. Folate administration in postmenopausal women is able to reduce high plasma homocysteine levels and to modify impaired endothelial function induced by hyperhomocysteinemia.

Effect of metformin on the growth hormone response to growth hormone-releasing hormone in obese women with polycystic ovary syndrome.

OBJECTIVE: Obese women with polycystic ovary syndrome (PCOS) show a marked growth hormone (GH) hyporesponsiveness to several stimuli. We aimed to evaluate the impact of insulin metabolism on the GH secretion impairment in these subjects in relation to food ingestion. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Nine obese women with PCOS. INTERVENTION(S): Metformin (1,500 mg/daily) was administered for three months. The study protocol, which was performed before and after therapy, included hormonal and lipid assays, oral glucose tolerance test (75 g), euglycemic hyperinsulinemic clamp, and growth hormone-releasing hormone (GHRH) test (50 microg/ev), both on fasting and after a standard meal. MAIN OUTCOME MEASURE(S): Growth hormone response to GHRH (expressed as the area under the curve) in different experimental conditions. RESULT(S): The preprandial GH response to GHRH was not modified by the therapy, whereas a significant increase (P<.05) occurred in the postprandial GH secretion, thus resembling the response of obese normal persons. This change was accompanied by a trend towards improvement, though not statistically significant, of all the evaluated glycoinsulinemic parameters. A significant reduction in cholesterol (P<.01) and androstenedione (P<.05) and an increase in sex hormone-binding globulin (P<.05) were also achieved. CONCLUSION(S): These data suggest that metformin is able to affect GH secretion in obese women with PCOS, even with minimal metabolic modifications.