Aging, Insulin Resistance
Conditions
Keywords
Aging, Hormones, Insulin resistance
Brief summary
The goal of this research study is to study the effect of testosterone or estrogen on blood sugar control and fat metabolism. Changes in hormone levels with age may affect risk factors for heart disease such as diabetes. Diabetes is a glandular condition associated with lack of the hormone insulin or an insensitivity to it resulting in problems with blood sugar control and fat metabolism. The effect of commonly used hormonal supplements such as testosterone by older adults on insulin and body composition is not well understood. In this study, the role of testosterone and estrogen on your ability to control blood sugar and your body composition will be assessed. The investigators plan to study 60 subjects. All of these subjects will be healthy older men between the ages of 60-85 years old who are not on testosterone therapy. Subjects that are screened who have any clinically significant abnormalities detected on their screening physical exam or laboratory testing (e.g. Prostate Specific Antigen \> 4), who have a history of prostate cancer, polycythemia, or who cannot take testosterone will not be included. If a subject is eligible to participate after initial screening, that subject will take medications to adjust their hormone levels and have tests performed that measure insulin sensitivity and adiposity before and after these hormone medications. The outcomes that will be measured are: 1) insulin sensitivity, 2) hormone levels (total and free testosterone levels, sex hormone-binding globulin levels) and 3) body composition and abdominal adiposity.
Interventions
DRUGTestosterone
Testosterone gel
DRUGEstrogen
Estrogen patch
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
60 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* males age 60-85 years * non-diabetic fasting glucose and 2-hour oral glucose tolerance test (OGTT) * overall good general medical health and signed informed consent * willing to travel to West Los Angeles VA and University of California, Los Angeles in Los Angeles, California
Exclusion criteria
* any clinically significant abnormalities detected on screening physical exam or laboratory testing (e.g. prostate specific antigen \> 4) * or other symptom or history of a significant underlying medical or psychiatric illness * BMI \< 20 or \> 40 * subjects already on testosterone therapy or medications that might influence glucose regulation or hormone levels * subjects with a history of deep venous thromboses, pulmonary embolism, breast cancer, prostate cancer, polycythemia or other contraindications to estrogen or testosterone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 6 weeks | As measured by change in insulin levels pre- and post-hormone changes |
Countries
United States
Participant flow
Recruitment details
Recruitment methods included flyers and advertisement in local newspapers. Healthy Veteran and community participants who responded to to advertisement were screened by telephone for exclusion criteria. If no exclusion criteria were reported, participants were scheduled for a screening history and physical.
Participants by arm
| Arm | Count |
|---|---|
| +T +E +Testosterone, +Estrogen
Testosterone: Testosterone gel
Estrogen: Estrogen patch | 9 |
| +T -E +Testosterone, -Estrogen
Testosterone: Testosterone gel | 8 |
| -T +E -Testosterone, +Estrogen
Estrogen: Estrogen patch | 8 |
| -T -E -Testosterone, -Estrogen | 8 |
| Total | 33 |
Baseline characteristics
| Characteristic | +T +E | +T -E | -T +E | -T -E | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 5 Participants | 6 Participants | 4 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 3 Participants | 2 Participants | 4 Participants | 14 Participants |
| Age, Continuous | 67 years STANDARD_DEVIATION 8 | 66 years STANDARD_DEVIATION 5 | 69 years STANDARD_DEVIATION 6 | 63 years STANDARD_DEVIATION 3 | 66 years STANDARD_DEVIATION 6 |
| Body-Mass-Index | 27.1 kilogram/meter squared STANDARD_DEVIATION 4.9 | 28.6 kilogram/meter squared STANDARD_DEVIATION 4.3 | 28.2 kilogram/meter squared STANDARD_DEVIATION 4.1 | 29.0 kilogram/meter squared STANDARD_DEVIATION 2.9 | 28.2 kilogram/meter squared STANDARD_DEVIATION 4 |
| Region of Enrollment United States | 9 participants | 8 participants | 8 participants | 8 participants | 33 participants |
| Sex/Gender, Customized Male | 9 participants | 8 participants | 8 participants | 8 participants | 33 participants |
| Total testosterone | 419.6 nanogram/deciliter STANDARD_DEVIATION 146.5 | 418.9 nanogram/deciliter STANDARD_DEVIATION 207.7 | 480.0 nanogram/deciliter STANDARD_DEVIATION 231.7 | 558.3 nanogram/deciliter STANDARD_DEVIATION 362.9 | 467.7 nanogram/deciliter STANDARD_DEVIATION 242 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 8 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Insulin Sensitivity
As measured by change in insulin levels pre- and post-hormone changes
Time frame: 6 weeks
Population: Two participants had missing values post-intervention therefore number of participants analyzed total 31.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| +T +E | Insulin Sensitivity | -0.16 micro International Units/mL | Standard Deviation 10.8 |
| +T -E | Insulin Sensitivity | 2.62 micro International Units/mL | Standard Deviation 5.47 |
| -T +E | Insulin Sensitivity | -0.50 micro International Units/mL | Standard Deviation 2.54 |
| -T -E | Insulin Sensitivity | 1.83 micro International Units/mL | Standard Deviation 4.24 |
Comparison: The major outcome variable being presented is changes in insulin levels. Changes in insulin levels were analyzed using an ANCOVA model that adjusted for baseline insulin and age.p-value: 0.042ANCOVA
Comparison: The major outcome variable being presented is changes in insulin levels. Changes in insulin levels were analyzed using an ANCOVA model that adjusted for baseline insulin and age.p-value: 0.023ANCOVA