Hypoandrogenism, Obesity
Conditions
Keywords
Flow-mediated dilatation, Clomiphene citrate, sICAM-1, sVCAM-1, sE- Selectin, Endothelial function, Cardiovascular risk, Endocrine System Diseases, Selective Estrogen Receptor Modulators, Estrogen Receptor Modulators, Infertility, Male, Endothelial Progenitor Cells, Obesity, Testosterone
Brief summary
Hypogonadism is a clinical condition that can be associated with obesity in man. Controversy exists regarding if its a condition that needs to be treated. The standard Testosterone Therapy is associated with increase in cardiovascular risks, according to some studies, and leads to infertility. The use of Clomiphene Citrate in this sub population of obese man as an alternative treatment option is not well studied. The aim of this protocol is to evaluate the cardiovascular risks, metabolic and hormonal parameters in a double blinded randomized placebo trial.
Detailed description
Hypogonadism (low testosterone level) in obese man is a clinical condition which treatment is controversial. Most of this controversy remains regarding the association between cardiovascular risk elevation and Testosterone replacement therapy in some studies. This protocol is a double blinded randomized placebo trial and 2 groups will be followed. The primary end-point of this research is the correlation between the serum testosterone and flow-mediated dilatation of the brachial artery (FMDAB), circulating levels of sICAM-1, sVCAM-1, E-selectin and progenitor endothelial cells. The secondary end-points include: (1) the evaluation of metabolic parameters: weight, abdominal circumference, glycaemia, total cholesterol, fractions and triglycerides, homeostasis model assessment index (HOMA) and bioelectrical impedance parameters; and (2) hormonal parameters: total testosterone levels, sex hormone-binding globulin (SHBG), Luteinizing Hormone (LH) , Follicle stimulating hormone (FSH) and Estradiol.
Interventions
DRUGClomiphene Citrate
50 mg orally daily during 12 weeks
DRUGPlacebo
1 pill orally daily during 12 weeks
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
University of Sao Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
randomized, double blinded, placebo-controlled, parallel group, single-center study
Intervention model description
78 patients were randomized (1:1) to receive Clomiphene Citrate (CC) 50 mg during 12 weeks or placebo (PLB). MAIN OUTCOME MEASURES: flow-mediated dilatation of the brachial artery (FMDAB), circulating levels of sICAM-1, sVCAM-1, E-selectin and progenitor endothelial cells. Secondary endpoints: Body mass index (BMI), abdominal circumference (AC), glycaemia, total cholesterol, fractions and triglycerides, HOMA-IR index, bioelectrical impedance parameters, Adam questionnaire and hormonal parameters (total testosterone levels, SHBG, LH, FSH and Estradiol).
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* ADAM questionnaire positive for 3 or more questions * Total serum Testosterone lower than 300 ng/dL in two different occasions, within a 1-week minimum interval. This blood sample must be collected between 8 and 11 a.m. * Low or Inappropriate normal serum Luteinizing hormone (LH) level * ATP III Metabolic Syndrome Criteria * Obesity - BMI over 30 kg/m2
Exclusion criteria
* Systemic illness, such Rheumatoid Arthritis, Cushing disease, liver insufficiency or renal insufficiency. -Use of certain medications (opiates, high-dose glucocorticoid therapy, methadone) * Eating disorders * Testicular volume below 4 mL * Use of recreational drugs * Excessive exercise practice * Men in treatment for prostatic cancer * Hyperprolactinaemia * Hemochromatosis * History of headache * Systolic blood pressure lower than 100 mmHg * Previous adverse reactions to nitrate compounds * Diabetes over 10 years of diagnosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Function | baseline up to 12 weeks | 1. Flow-mediated dilatation of the brachial artery (FMDAB): Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter. 2. Icam, vcam and selectin 3. Endothelial progenitor cels |
| Total Testosterone | baseline up to 12 weeks | electrochemical luminescence analysis in blood sample |
Countries
Brazil
Outcome results
None listed