There are 2 clinical trials
This is cross-over, randomized clinical trial, with objective to evaluate the effects of low-dose oral hormone therapy and non-oral hormone therapy on endothelial function markers (fibrinogen, von Willebrand factor, c-reactive protein), natriuretic peptide and on anthropometric, metabolic and hormonal variables in early and healthy postmenopausal women and analyzing polymorphisms in the estrogen receptor gene and FTO polymorphisms Patients will be randomized to receive oral hormone treatment or non-oral hormone treatment The investigators hypothesis is that a different genotypes in the receptor estrogen gene and FTO may have an influences on treatment response in metabolic markers and cardiovascular risk
Influence of 2 polymorphisms (rs9939609 and rs8050136) on the effect of different treatment regimens.
Description: Influence of 4 polymorphisms (PVUII, ALUI, RSAI and BSTUI) on the effect of different treatment regimens. Change from Baseline in weight, waist circumference, BMI, systolic and diastolic blood pressure, fasting glucose, glucose at 120 min, Fasting insulin, HOMA, Cholesterol, HDL-c, LDL-c, Triglycerides, Von Willebrand Factor, Fibrinogen, Testosterone and C-reactive protein at six months.
Measure: Polymorphisms of estrogen receptor Time: six monthsDescription: Influence of 2 polymorphisms (rs9939609 and rs8050136) on the effect of different treatment regimens. Change from Baseline in weight, waist circumference, BMI, systolic and diastolic blood pressure, fasting glucose, glucose at 120 min, Fasting insulin,HOMA, Cholesterol, HDL-c, LDL-c, Triglycerides, Von Willebrand Factor, Fibrinogen, Testosterone and C-reactive protein at six months.
Measure: Polymorphisms in the fat mass-and obesity-associated (FTO) gene Time: Six MonthsDescription: To assess the effects of oral low-dose and non-oral hormone therapy (HT) on ultra-sensitive C reactive protein (CRP), atrial natriuretic peptide (ANP), and cardiovascular risk factors in postmenopause.
Measure: Effects of hormone therapy on C reactive protein, atrial natriuretic peptide and cardiovascular risk factors in postmenopause. Time: Six monthsObesity is a widespread disease with increasing prevalence and associated with serious secondary complications. So far, the origin of the disease, regardless of an existing positive energy balance, is not fully understood. In addition to environmental factors, the genetic background plays an important role in the pathogenesis of obesity. Of common genetic polymorphisms, variants in the fat mass and obesity associated gene (FTO) locus have the highest effect size on body weight. Animal and first clinical studies indicate that FTO variants interact with dopamine signaling in the brain, thus influencing the risk of overweight. In fact, preliminary results indicate that enhancing dopamine signaling with the dopamine agonist bromocriptine, depending on the FTO genotype, either induces weight loss or has a neutral effect on body weight. The planned clinical trial serves to develop a genotype-specific and thus individualized therapy approach for obesity. The influence of dopamine agonist therapy on weight loss as a function of the FTO (rs8050136) genotype is to be tested. Here, the greatest weight loss is expected to occur in subjects carrying the homozygous risk-allele (AA). So far, there are only a few established conservative therapy forms of obesity, so that bariatric interventions with an increasing rate are necessary to achieve weight loss and thus a reduction in overall morbidity and mortality. Among the approved drug therapies for obesity, bromocriptine is commonly used. In addition, some interventions require injections. An early, conservative individualized, genotype-specific treatment with little side-effects would enable simple treatment of obesity. Study design: 150 obese (BMI > 30) subjects (50 / study center) will be enrolled in the study. The subjects will be stratified according to their FTO genotype (rs8050136). Subjects will be randomized into placebo or bromocriptine treatment group. Treatment will last for 18 weeks and a follow-up will be performed 30 weeks after baseline.
The influence of dopamine agonist therapy on weight loss as a function of the FTO (rs8050136) genotype is to be tested.
The subjects will be stratified according to their FTO genotype (rs8050136).
Interaction between FTO genotype and treatment on change in body weight.. Interaction between FTO (single nucleotide peptide) SNP rs8050136 genotype and treatment (bromocriptine or placebo) on change in body weight.. Effect of bromocriptine vs. placebo on body weight.
Description: Interaction between FTO (single nucleotide peptide) SNP rs8050136 genotype and treatment (bromocriptine or placebo) on change in body weight.
Measure: Interaction between FTO genotype and treatment on change in body weight. Time: 18 weeksDescription: Dietary intake will be monitored by food diaries
Measure: Effect of bromocriptine vs. placebo on dietary intake Time: 18 weeksDescription: Processing of food cues in the brain will be assessed by functional magnetic resonance imaging before and after treatment with bromocriptine or placebo
Measure: Effect of bromocriptine vs. placebo on processing of food cues in the brain Time: 18 weeksDescription: Body fat distribution will be assessed by magnetic resonance imaging and magnetic resonance spectroscopy before and after treatment with bromocriptine or placebo
Measure: Effect of bromocriptine vs. placebo on body fat distribution Time: 18 weeksDescription: Whole body insulin sensitivity will be quantified from 5 point 75g oral glucose tolerance test before and after treatment with bromocriptine or placebo
Measure: Effect of bromocriptine vs. placebo on whole body insulin sensitivity Time: 18 weeksDescription: Insulin secretion will be quantified from 5 point 75g oral glucose tolerance test before and after treatment with bromocriptine or placebo
Measure: Effect of bromocriptine vs. placebo on insulin secretion Time: 18 weeksDescription: Glucose tolerance will be assessed by 75g oral glucose tolerance test before and after treatment with bromocriptine or placebo
Measure: Effect of bromocriptine vs. placebo on glucose tolerance Time: 18 weeksDescription: Brain insulin sensitivity will be assessed by functional magnetic resonance imaging combined with intranasal insulin administration before and after treatment with bromocriptine or placebo
Measure: Effect of bromocriptine vs. placebo on brain insulin sensitivity Time: 18 weeksDescription: Resting energy expenditure will be assessed by indirect calorimetry before and after treatment with bromocriptine or placebo
Measure: Effect of bromocriptine vs. placebo on resting energy expenditure Time: 18 weeksDescription: Physical activity will be monitored using an accelerometer
Measure: Effect of bromocriptine vs. placebo on physical activity Time: 18 weeks