Anabolic and Inflammatory Responses to Short-Term Testosterone Administration in Older Men
| Status: | Completed |
|---|---|
| Conditions: | Orthopedic |
| Therapuetic Areas: | Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 60 - 85 |
| Updated: | 5/10/2018 |
| Start Date: | March 2009 |
| End Date: | December 2015 |
Skeletal muscle loss is a common consequence of aging and in some individuals reaches a level
that compromises health and quality of life. Age-associated increases in cytokine and
inflammatory signaling may be important contributors to this process.
The investigators will assess the practical question of whether testosterone injection and
gel application elicit similar responses. Resistance exercise will be used as a means of
stimulating both inflammatory and anabolic responses in skeletal muscle. In order to assess
the effects of testosterone on these responses, subjects will perform resistance exercise on
two occasions separated by 7 days. The first session will be performed prior to the
initiation of testosterone and/or medrol therapy and the second session will be performed
after receiving therapy for 7 days.
that compromises health and quality of life. Age-associated increases in cytokine and
inflammatory signaling may be important contributors to this process.
The investigators will assess the practical question of whether testosterone injection and
gel application elicit similar responses. Resistance exercise will be used as a means of
stimulating both inflammatory and anabolic responses in skeletal muscle. In order to assess
the effects of testosterone on these responses, subjects will perform resistance exercise on
two occasions separated by 7 days. The first session will be performed prior to the
initiation of testosterone and/or medrol therapy and the second session will be performed
after receiving therapy for 7 days.
4 groups of healthy men aged 60 - 85 years were studied over 15 days, in 2 distinct time
periods, pre-treatment and treatment.
Pre treatment week from study day -7 to study day -1. Treatment week from study day 1 to
study day 8.
Groups:
1. Testosterone by injection (100mg testosterone enanthate) administered on study day 1.
2. Testosterone by gel application (10g/day Androgel 1%) administered daily beginning on
study day 1 through study day 7.
3. Methylpredisone (Medrol) dose pack beginning on study day 1 (24mg) and decreasing by 4mg
each day, with an additional 4mg taken on study day 7. Study day 1 (24mg), study day 2
(20mg), study day 3 (16mg), study day 4 (12mg), study day 5 (8mg), study day 6 (4mg),
study day 7 (4mg).
4. Testosterone by injection (100mg testosterone enanthate) administered on study day 1 and
Methylpredisone (Medrol) dose pack beginning on study day 1 (24mg) and decreasing by 4mg
each day, with an additional 4mg taken on study day 7. Study day 1 (24mg), study day 2
(20mg), study day 3 (16mg), study day 4 (12mg), study day 5 (8mg), study day 6 (4mg),
study day 7 (4mg).
Subjects were asked to fill out the Brief Fatigue Inventory daily for all 15 days.
Subjects were studied at the clinical research center before treatment (study day 1) and
after treatment (study day 8). Resistance exercise was performed on study days 1 and 8. Blood
was drawn before and after exercise for measurement of serum cortisol. Subjects were asked to
return to the clinical research center each day during the treatment week (study days 1-8)
for blood draws for measurement of total testosterone, estradiol and C-reactive protein
(CRP). Labs were drawn on study days 1 and 8 for complete blood count, comprehensive
metabolic panel and lipid panel.
Part 1:
In this part of the project we will study the acute response to testosterone treatment
between two groups of subjects, comparing two methods of administration (injection vs.
topical gel) in order to obtain pilot information for a subsequent, randomized, blinded
long-term investigation.
Part 2:
In this part of the project we will study the acute response to Medrol (methylprednisolone)
taken over 7 days with or without testosterone (given as 100mg IM) in order to obtain pilot
information for a subsequent, randomized, blinded long-term investigation.
periods, pre-treatment and treatment.
Pre treatment week from study day -7 to study day -1. Treatment week from study day 1 to
study day 8.
Groups:
1. Testosterone by injection (100mg testosterone enanthate) administered on study day 1.
2. Testosterone by gel application (10g/day Androgel 1%) administered daily beginning on
study day 1 through study day 7.
3. Methylpredisone (Medrol) dose pack beginning on study day 1 (24mg) and decreasing by 4mg
each day, with an additional 4mg taken on study day 7. Study day 1 (24mg), study day 2
(20mg), study day 3 (16mg), study day 4 (12mg), study day 5 (8mg), study day 6 (4mg),
study day 7 (4mg).
4. Testosterone by injection (100mg testosterone enanthate) administered on study day 1 and
Methylpredisone (Medrol) dose pack beginning on study day 1 (24mg) and decreasing by 4mg
each day, with an additional 4mg taken on study day 7. Study day 1 (24mg), study day 2
(20mg), study day 3 (16mg), study day 4 (12mg), study day 5 (8mg), study day 6 (4mg),
study day 7 (4mg).
Subjects were asked to fill out the Brief Fatigue Inventory daily for all 15 days.
Subjects were studied at the clinical research center before treatment (study day 1) and
after treatment (study day 8). Resistance exercise was performed on study days 1 and 8. Blood
was drawn before and after exercise for measurement of serum cortisol. Subjects were asked to
return to the clinical research center each day during the treatment week (study days 1-8)
for blood draws for measurement of total testosterone, estradiol and C-reactive protein
(CRP). Labs were drawn on study days 1 and 8 for complete blood count, comprehensive
metabolic panel and lipid panel.
Part 1:
In this part of the project we will study the acute response to testosterone treatment
between two groups of subjects, comparing two methods of administration (injection vs.
topical gel) in order to obtain pilot information for a subsequent, randomized, blinded
long-term investigation.
Part 2:
In this part of the project we will study the acute response to Medrol (methylprednisolone)
taken over 7 days with or without testosterone (given as 100mg IM) in order to obtain pilot
information for a subsequent, randomized, blinded long-term investigation.
Inclusion Criteria:
- Age: 60-85
- Gender: Male
Exclusion Criteria:
- Exclusionary medications will be an anticoagulant (Coumadin) because of the risk of
bleeding during the biopsy procedure. Additional medications which will be disallowed
for participation include: anabolic steroids, nitrates, antihistamines, and
glucocorticoids.
- The subjects must be able to successfully complete an exercise stress test using the
Bruce protocol . Subjects will be excluded without exercise testing, with a history of
angina that occurs with exertion or at rest, or a myocardial infarction within the
last 12 months. Subjects that demonstrate ³0.1 milliVolts (mV) horizontal or
downsloping ST segment depression, a drop in systolic blood pressure of ³10 mm Hg,
and/or frequent or repetitive arrhythmias (defined as ³10 premature ventricular
contractions (PVC)/min, or couplets) during the stress test will be excluded.
- Subjects with LDL cholesterol above 200 mg/dL will be excluded .
- Any man with a history of breast cancer or prostate cancer, or any indication of an
occult carcinoma from an elevation of prostate specific antigen (PSA) above 4.0 mg/L
(53), or severe benign prostatic hypertrophy (BPH) by history (frequent urination,
reduced stream) will be excluded.
- Subjects with liver dysfunction evidenced by a history of hepatitis B or hepatitis C,
or by a three-fold elevation of liver enzymes (Alk phos, alanine aminotransferase
(ALT), aspartate amino-transferase (AST) above normal on screening will be excluded
from the study.
- Any subject with a blood pressure on three consecutive measurements taken at one week
intervals that has a systolic pressure ³ 140 or a diastolic blood pressure ³ 90 will
be excluded.
- Any subject who has a major medical illness such as diabetes, chronic obstructive
pulmonary disease, or sleep apnea will be excluded. Moreover, subjects will not have a
recent history of smoking tobacco. Morbidly obese older men (BMI > 35) will also be
excluded.
- Subjects will evidence of kidney disease (serum creatinine > 2.0mg/dl) will be
excluded from participation.
- Any subject with thyroid disease as determined by an abnormal thyroid stimulating
hormone (TSH) level will be excluded from participation.
- Any subject testing positive for HIV will be excluded .
- Allergy to iodine, a component of Betadine which is used to prepare the subject's skin
for invasive procedures, will be cause for exclusion from this study.
- Men with serum total testosterone concentrations greater than 500 ng/dL will be
excluded.
- Subjects who engage in high intensity resistance training on a regular basis will be
excluded.
- Subjects with a known coagulation disorder or with clinical evidence indicative of a
bleeding disorder (easy bruising, "free bleeders") will not be enrolled in this study
due to potential problems that could arise from muscle biopsy procedures.
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