Remember When You Had Energy ?

Remember When You were happy? Remember When You were Not Depressed?

Remember When You Had Passion? Remember When You were Confident About Your Sexual Performance?

 Remember When You were Leaner and Stronger? Remember When You had Better Body

 You Can Make Those Memories into a Reality!

AndroGel

Side Effects May Include:

Testosterone

History
Berthold in 1849 - castrated roosters In 1889 Charles-douard Brown-Sequard injected testicular extracts from testicles of dogs and guinea pigs on himself at the age of 72. He claimed a remarkable return of physical strength and endurance, a rejuvenated bowel system, and enhanced mental capacity. Butenandt in 1931 isolation of steroidal androgens Butenandt and Hanish in 1935 chemically synthesized testosterone

Background
Oral T (1930s) - Quickly eliminated by first pass effect Oral versions were replaced by its alkylated form: 17 alpha-methyl testosterone Compressed into pellets and implanted SubQ Injectable T esters (1950s) Transdermal patches (1990s) First gel (2000) Injectable form under clinical trials (2004-2009)

T Gel
When an open system of hydroalcoholic gel of a steroid is applied to the skin, the steroid is rapidly absorbed into the stratum corneum, which forms a reservoir and acts as a rate-controlling membrane. The steroid then gradually diffuses from this skin reservoir over several hours, reaching steady-state levels in the serum

Mechanism

 Objective: To determine the effects of a 12-week long-acting testosterone by measuring functional capacity and ventilatory efficiency in individuals with chronic heart failure.

 Hypothesis: Relative hypotestosteronemia is involved in impairment of skeletal function and exercise tolerence in heart failure. The hypothesis is that treatment will improve FC and VE via muscle performance.

Methods
- 70 elderly male patients with moderate to severe CHF - At baseline and end of study, tests and measurements included: blood sample, ECG, muscle strength assessment, cardiopulmonary exercise test, 6-minute walk test, BRS - Patients received either IM long-acting testosterone or IM saline

Results
- Changes in T correlated significantly with changes in peak VO2 and MVC, improves VE/VCO2 slope, largemuscle performance, glucose metabolism and BRS - Greater increase in peak VO2 and MVC in those with lower baseline T than normal T, but not significant

Changes from baseline after 3 months of TST

Significant Change Insignificant Change

VO2
MVC VE/VCO2 slope 6MWT Hematocrit

PSA levels
Liver and renal function Hemoglobin levels Total cholesterol Triglycerides

Body weight, BMI

BRS

CRP

Conclusions and Caveats

- Long-term testosterone supplementation DOES improve functional capacity and baroreflex control of heart rate, muscle strength, and glucose metabolism in elderly patients with CHF

- Medications taken through study - Short follow up, cannot generalize through clinical outcomes

Purpose
Determine the effects of 6 month treatment with testosterone gel on intermediate-frail and frail elderly men
o Muscle mass and Strength o Physical Function o Quality of life

Criteria for Frailty

1. Unintentional Weight Loss of More than 10lb in the preceding year 2. Self reported exhaustion 3. Low physical activity 4. Slow walk time 5. Low handgrip strength Intermediate-Frail = 1 to 2 criteria Frail = 3 or more criteria

Population
8260 community-dwelling men over the age of 65 were recruited Exclusion criteria:
o o o o o Not Frail Raised PSA Prostate Pathology T>12nmol/l Moderate to severe peripheral vascular disease

274 were were candidates for the trial

o 130 received testosterone gel o 132 received placebo gel.

Intervention
Study Group Received T gel at a dose of 50mg/day for 6 months The dose was adjusted to 75mg/day or 25mg/day according to serum T at day 10 and 3 months Target Range of T levels 18-30nmol/l

Took measurements at baseline and 6 months of:

Muscle Strength
o o o o o Isokinetic knee extension Isometric knee extension Isokinetic knee flexion Isometric knee flexion Grip Strength

Methods

Physical Function Body Composition

o LBM o FM

Quality of Life (The aging males' symptoms (AMS)

rating scale)

o Somatic Subscale o Psychological Subscale o Sexual Subscale

Methods
Monitoring:
o T, LH, FSH and SHBG o Performed at baseline, 10days, 3 months, and 6 months

Total Testosterone

Free Testosterone

Luteinizing Hormone

Adjusted Difference T-Placebo

P-Value

IME LBM

8.6 Nm 1.1 lb

.04 <.001

FM
Somatic Subscale Sexual Subscale

-.6 lb -1.2

.02 .04

-1.3

.02

Authors Conclusions
increasing low or borderline-low testosterone concentrations to the middle of the normal range in elderly men for 6 months improved lower limb muscle strength compared with placebo. Testosterone increased LBM and decreased FM along with improvement of somatic and sexual symptoms

 Free Testosterone (T) should be higher to prevent mobility limit (disability, institutionalized life, quality of life, death)

Study Methods
Patients: from Framingham study Age range (51-70 yr)
o Mobility (N=1111) o Walking speed (N=693)

Study length: 6.6 years

Mobility Limitation
Using modified Roscow-Breslau questionaire
o Heavy works o Half-mile walk, unassisted o Walk up and down stairs

Responses:
o No help o Use device o Human assistance Minimal or maximal o Almost never

Physical Performance
Hand grip:
o Each hand o Jamar hydraulic dynamometer

SPBB:
o Standing balance o Walking speed o Chair stand

Cross-sectional analyses of low FT association with SPBB

Longitudinal analyses of low FT association with mobility limitation

They conclude: Low FT = 57% higher risk of mobility limitation 68% higher risk of worsening limitation no data

Authors conclusion
Lower Free Testosterone (FT) = higher risk of mobility limitation (disability, institutionalized life, quality of life, death) FT is associated with SPBB and walking speed Small but significant effect No conclusion whether T therapy might work

Advantage Wider age range Included age, disease history

Limitations
Only in white men Some patients did not return (possible, really sick patients) Can only consider association, not causal relationship

Patients Wave 1996, 12,203 Wave 1

1999

Wave 2 Wave 3

2001, 2004 20082009

10,940 3,274

Frailty Assessment
Domains:
Fatique Resistance (can you climb a flight of stairs) Ambulation (walk one block) >5 illnesses >5% weight loss

Cross-sectional association of low FT and frailty

Longitudinal association of low FT and frailty

Authors Conclusion
Frailty is associated with:
o Lower FT o Higher LH

From correlation of FT and weight loss, sarcopenia patients may get benefit from therapy.