Influence of Aromatase Inhibition on Hepatic- and Cardiac Function in Severe Obese Men

Study Overview
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Brief Summary
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It seems plausible that increased aromatase activity in obese men, as a result of a larger fat mass, is responsible for decreased levels of testosterone. Therefore aromatase inhibition increases testosterone levels, which may affect hepatic and cardiac function. In this intervention study two groups of hypogonadal obese men are compared. Group A is treated with Letrozole 2.5 mg (aromatase inhibitor) once every two days during four months; a group with normal testosterone and low oestrogen concentrations. Group B is treated with placebo once every two days during four months; this group will retain low testosterone - and high oestrogenic concentrations. The primary objective of the study is to evaluate effects of changed sex steroids in obese men on hepatic and cardiac function.

Official Title
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Influence of the Aromatase Inhibitor Letrozole on Heart and Liver Function in Obese Men

Conditions
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Obesity

Intervention / Treatment
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* Drug: Letrozole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese male subjects Planned for gastric bypass (BMI > 30 kg/m²) low testosterone levels age between 20 and 65 Exclusion Criteria: Primary hypogonadism or secondary hypogonadism due to genetic causes (Kallman syndrome etc.), tumours, infiltrative diseases, infections, pituitary apoplexy, trauma, critical illness, chronic systemic illness or intentional. Treatment with corticoids, opiates (on a daily basis), androgen- or estrogen analogs or CYP2A6 substrates (Dexmedetomidine, Ifosfamide, Methoxsalen, Miconazole, Tranylcypromine). Impaired renal function defined as serum-creatine > 1.5 mg/dL Clinically significant active cardiovascular disease including history of myocardial infarction within the past 6 months and/or heart failure (NYHA class III or IV) at the discretion of the investigator Cancer or any clinically significant disease or disorder, which in the investigator's opinion could interfere with the results of the trial Palpable prostate nodule or induration, Prostate-specific antigen (PSA) > 3 ng/mL, prostatism, untreated sleep apnea syndrome, erythrocytosis (hematocrit > 50%) or hyperviscosity. (cfr. Endocrine Society Clinical Practice Guideline by Bhasin S et al.) Known or suspected abuse of alcohol or narcotics

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole<br> | Drug: Letrozole<br>* One Letrozole 2.5 mg capsule every two days during four months<br>* Other names: Femara;|
| Placebo Comparator: Placebo comparator<br> | Drug: Placebo<br>* One placebo capsule every two days during four months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiac function parameters | heart function will be measured by echocardiography. | after 4 months intervention | 
| Hepatic function parameters | Baseline sex steroids will be measured by Liquid chromatography-mass spectrometry (LC-MS/MS) in fasting blood samples, before 10:00 am. Liver function will be analysed by a Nuclear Magnetic Resonance (NMR) recording | before intervention | 
| Hepatic function parameters | Baseline sex steroids will be measured by Liquid chromatography-mass spectrometry (LC-MS/MS) in fasting blood samples, before 10:00 am. Liver function will be analysed by a Nuclear Magnetic Resonance (NMR) recording | after 4 months intervention | 
| cardiac function parameters | heart function will be measured by echocardiography. | before intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucose metabolism | Glucose metabolism will be estimated by an oral glucose tolerance test (OGTT). | Before four months intervention. | 
| weight |  | Before intervention. | 
| weight |  | after four months intervention. | 
| glucose metabolism | Glucose metabolism will be estimated by an oral glucose tolerance test (OGTT). | Before intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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with disturbed glucose metabolism, without disturbed glucose metabolism