Effects of Testosterone and Fat Utilization

Testosterone Effects on Systemic Lipolysis and Whole Body Lipid Utilization

Evidence is accumulating that there are sex differences in energy and substrate metabolism. The positive or negative consequences of such metabolic differences between men and women need to be evaluated with respect to health outcomes. The importance of aberrant lipid metabolism in metabolic diseases such as obesity, diabetes and cardiovascular disease, makes understanding the distinction between "normal" vs aberrant critical to future treatment and prevention strategies. Sex differences in the effects of catecholamines on lipid metabolism and substrate oxidation in non-obese, healthy individuals, have been consistently observed. In addition, distinct differences in men and women exist in the distribution of body fat, with men typically having greater central adiposity than women. Accumulation of fat in the abdomen is associated with an increased risk for metabolic abnormalities such as hyperlipidemia and insulin resistance. In the current study, therefore, the role of testosterone in determining the sex differences in catecholamine mediated substrate metabolism and deposition of dietary fat into upper versus lower body adipose tissue depots will be addressed.

Study Overview

• Status: Completed
• Conditions: Healthy; Volunteers
• Intervention / Treatment: Drug: Aromatase Inhibitors; Drug: GnRH antagonist; Drug: Testosterone gel

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• normal weight (BMI of 23-29.9 kg/m2)
• not be highly trained (< 5hrs of moderate intensity, planned exercise per week).

Exclusion Criteria:

• Patients will be excluded if they have one or more of the following out-of-range values measured on a fasting blood sample:
• glucose <65 or > 110 mg/dl,
• insulin > 20 uU/ml,
• thyroid stimulating hormone <0.5 or >5.0 uU/ml,
• growth hormone >2.5 ng/ml.
• Subjects who may be:
• anemic (hemoglobin < 14.5 g/dl men ),

• have abnormal liver function tests:

  • alanine amino transferase > 47 U/l,
  • aspartate aminotransferase, > 47 U/l,
  • alkaline phosphatase <39 or >117 U/l) or
  • creatinine (<0.6 or >1.1 mg/dl).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Placebo Comparator: GnRH antagonist + Placebo Gel	Drug: Aromatase Inhibitors; Drug: GnRH antagonist
Active Comparator: GnRH antagonist + Testosterone Gel	Drug: Aromatase Inhibitors; Drug: GnRH antagonist; Drug: Testosterone gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dietary fat tracer for storage of meal derived fatty acids	50 uCi of [1-14C] oleic acid administered with an inpatient test meal	4 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Daniel Bessesen, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Rynders CA, Schmidt SL, Bergouignan A, Horton TJ, Bessesen DH. Effects of short-term sex steroid suppression on dietary fat storage patterns in healthy males. Physiol Rep. 2018 Jan;6(2):e13533. doi: 10.14814/phy2.13533.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2006
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 19, 2017
• First Posted (Actual): September 21, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2017
• Last Update Submitted That Met QC Criteria: September 19, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Androgens; Testosterone; Aromatase Inhibitors
• Other Study ID Numbers: 06-0010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No