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Taken from WWW.pubmed.gov (testosterone studies)
JAMA. 2008 Jan 2;299(1):39-52.
Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men:
a randomized controlled trial.
Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, Aleman A, Lock TM, Bosch JL, et al
Department of Geriatric Medicine, University Medical Center Utrecht, The Netherlands
CONTEXT: Serum testosterone levels decline significantly with aging. Testosterone supplementation to older men might
beneficially
affect the aging processes.
OBJECTIVE: To investigate the effect of testosterone supplementation on functional mobility, cognitive function, bone
mineral density,
body composition, plasma lipids, quality of life, and safety parameters in older men with low normal testosterone levels.
DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial of 237 healthy men between the
ages of 60 and
80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university
medical center in
the Netherlands.
INTERVENTION: Participants were randomly assigned to receive 80 mg of testosterone undecenoate or a matching placebo
twice daily
for 6 months.
MAIN OUTCOME MEASURES: Functional mobility (Stanford Health Assessment Questionnaire, timed get up and go test,
isometric handgrip strength, isometric leg extensor strength), cognitive function (8 different cognitive instruments),
bone mineral
density of the hip and lumbar spine (dual-energy x-ray absorptiometry scanning), body composition (total body
dual-energy x-ray
absorptiometry and abdominal ultrasound of fat mass), metabolic risk factors (fasting plasma lipids, glucose,
and insulin), quality
of life (Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules), and safety parameters
(serum prostate-specific
antigen level, ultrasonographic prostate volume, International Prostate Symptom score, serum levels of
creatinine, aspartate
aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, hemoglobin, and hematocrit).
RESULTS: A total of 207 men completed the study. During the study, lean body mass increased and fat mass
decreased in the
testosterone group compared with the placebo group but these factors were not accompanied by an increase
of functional mobility or
muscle strength. Cognitive function and bone mineral density did not change. Insulin sensitivity improved
but high-density
lipoprotein cholesterol decreased; by the end of the study, 47.8% in the testosterone group vs 35.5% in the
placebo group had
the metabolic syndrome (P = .07). Quality-of-life measures were no different except for one hormone-related
quality-of-life measure
that improved. No negative effects on prostate safety were detected.
CONCLUSION: Testosterone supplementation during 6 months to older men with a low normal testosterone
concentration did not affect
functional status or cognition but increased lean body mass and had mixed metabolic effects.
PMID: 18167405 [PubMed - in process]
Dr. Gordon's comments:
I applaud these researchers for their interest but lament their study design.
This is a good example of looking for the right
thing - benefit from testosterone (T) replacement - but, because of a lack of understanding, failing to
conduct a really meaningful study. In my experience oral T supplementation
is markedly inferior to injected T, and six months is not nearly enough time to allow the full benefits
of this therapy to appear.
Four to five months is often when beneficial changes begin. A study like this should last at least
fourteen to eighteen months.
I question:
Why was the study done on men who, by the authors' definitions,
had “low normal” T levels as opposed
to low levels?
Why was their criteria for inclusion in the study in part based on a “total” T level?
Compared to a free T
this is a poor test at any age, and essentially worthless in elderly men (See: "Testosterone Blood Tests").
Of interest, they excluded men who likely
had much more severe T deficiency, those with a recent stroke or heart attack, congestive heart
failure, diabetes, or an enlarged prostate.
What did the study find?
The study found a significant increase in muscle mass and decrease in fat
mass, but not an increase in leg or
hand strength. It is hard to understand how an increase in muscle bulk cannot result in more strength.
Indeed, an increase in strength, especially
leg strength, is one of the most frequently reported benefits of T replacement in my practice.
“I can get up
now without holding on to anything.” "I can walk up the stairs without pulling myself." Again,
the problem here is likely an inadequate T replacement
method and duration, and probably an insufficiently sensitive leg strength testing procedure.
I vigorously question the wisdom of the authors’ use of handgrip strength
to determine an effect of T therapy.
While it is true that most of our hand strength comes from the muscles of the forearm, some does come
from muscles within the hand.
The older we get the more of us
develop some of the very common Carpal Tunnel Syndrome (CTS) (pressure on the nerve in the wrist)
One consistent consequence of the
CTS is hand weakness. Although most people are unaware of it, muscle shrinkage in the thumb side of
the heel of the hand is
very common as we age. It is
very likely that a number of these men had a degree of the CTS, and one cannot expect
T replacement to correct an unrelated neurological problem.
The authors report that the T treated men suffered from a “significant”
fall in their HDL (good) cholesterol, from
an average of 46 to 38. The LDL
(bad) cholesterol fell only from 151 to 147 - not significant. In my experience T replacement often
ultimately results in substantial lowering of
the LDL, but this is with injections and not in just six months. The starting level of a 46 HDL is
not very good to begin with. What I find
appalling is that the men in this study had very high LDL levels, an average of 151, and apparently were
not being treated. The N.I.H.
and major health foundations all recommend an LDL below 100 if otherwise healthy, and below 70 if diabetes or
vascular disease is present. As a matter of
fact, I generally don’t treat patients with T if they refuse to address, with medication, LDL
levels above 110.
The authors reported a non-significant increase in the number of men
having the metabolic syndrome. This was found
in both the treated and placebo groups. I think this is a
result of a basic flaw in their definition of the metabolic syndrome.
The authors reported an increase in insulin sensitivity.
A decrease in insulin sensitivity is a fundamental component
of adult onset (type II) diabetes, a widespread and devastating
disease. They thought so little of this critically important link between T deficiency and diabetes,
however, that they neglected to mention it in
their conclusions.
What did the study not find?
The lack of finding an increase in strength is addressed above.
They also found no detectable difference in
bone density or in cognitive function. I question the use of bone density
as an effect parameter in men who usually have minimal problems with osteoporosis, and any
potential change is certainly going to take much longer than
six months. I have had many
patients tell me of improvement in mental ability, but again this is with injected T.
The authors reported that: “Quality-of-life measures were no different
except ...” I’m guessing from their
inference that the “except”
had something to do with sex. Aside from that almost universal benefit, my patients
routinely report profound changes in their lives, that they’re different people, that they have new lives.
In summary, these men were treated with inadequate T replacement therapy
for a much too brief period of time.
The authors did find the well documented relationship between T deficiency and type II diabetes and,
I presume, loss of sexuality. Their
finding of significant fat loss and muscle gain, but without an improvement in strength, is
self-contradictory and not believable.
Finally, in the study itself the authors stated, “... ; most of the
participants were healthy and had no
important preexisting
health problems.” This assertion is mind boggling in the face of an average LDL cholesterol of 151.
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