| Mr. Softy 2005-12-20, 5:51 pm |
| Testosterone Replacement May Be Helpful in Alzheimer Disease CME
http://www.medscape.com/viewarticle/519806
News Author: Laurie Barclay, MD
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Dec. 15, 2005 - Testosterone replacement therapy improves quality of life
for patients with Alzheimer disease (AD), according to the results of a
randomized, double-blind study reported in the December 12 Early Release
issue of the Archives of Neurology.
"There is a compelling need for therapies that prevent, defer the onset,
slow the progression, or improve the symptoms of AD," write Po H. Lu, PsyD,
from the university of California, Los Angeles, and colleagues. "Hormonal
therapies for AD have been the focus of research attention in recent
years.... In the male brain, testosterone is converted to estrogen by
aromatase enzymes; therefore, testosterone can exert its effects on
cognition independently or indirectly via conversion to estrogen."
In this 24-week, parallel-group study, 16 male patients with AD and 22
healthy male control subjects were randomized to receive testosterone or
placebo in the form of hydroalcoholic gel (75 mg) applied daily to the skin.
Primary outcomes were cognitive functioning measured with the Alzheimer's
Disease Assessment Scale-Cognitive Subscale, California Verbal Learning
Test, Block Design Subtest, Judgment of Line Orientation, Developmental Test
of Visual-Motor Integration; neuropsychiatric symptoms measured with the
neuropsychiatric inventory; global functioning measured with the Clinician's
Interview-Based Impression of Change; and quality of life measured with the
Quality of Life-Alzheimer Disease Scale.
For the men with AD, those receiving testosterone had greater improvements
in the scores on the caregiver version of the quality-of-life scale (P =
..01). At end of study, there were no significant treatment group differences
in the cognitive scores. However, on measures of visuospatial functions,
testosterone treatment was associated with numerically greater improvement
or less decline than with placebo.
In the healthy control group, there was a nonsignificant trend toward
greater improvement in self-rated quality of life with testosterone than
with placebo (P = .09). For the remaining outcome measures, there was no
apparent difference between the treatment groups. Testosterone treatment was
well tolerated, and there were few adverse effects compared with placebo.
"Results suggest that testosterone replacement therapy improved overall
quality of life in patients with AD," the authors write. "Testosterone had
minimal effects on cognition."
Study limitations include possibly suboptimal compliance with treatment or
poor absorption of the testosterone gel; small sample sizes; large number of
outcome variables; failure to use low testosterone level as an inclusion
criterion; predominantly white sample; study instruments lacking sensitivity
to detect small changes; short duration; and use of proxy reports of quality
of life.
"The present results should be considered preliminary and do not warrant
routine treatment of AD and healthy control men with testosterone," the
authors conclude. "Future studies with larger sample sizes are needed before
clinical decisions regarding testosterone therapy can be rationally based.
For men with compromised quality of life, as reflected on the type of
measure employed in this study, and who suffer from low serum T levels,
testosterone therapy may be a reasonable consideration."
The John Douglas French Alzheimer's Foundation, National Institute on Aging,
and the Sidell-Kagan Foundation supported this study. Unimed
Pharmaceuticals, Inc, supplied testosterone and placebo gel.
Arch Neurol. Posted online December 12, 2005.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Identify neuropsychological outcomes associated with higher testosterone
levels in older men.
Specify neuropsychiatric, quality-of-life, and cognitive outcomes improved
with testosterone therapy in older men.
Clinical Context
Testosterone appears to have multiple neuropsychiatric effects, and these
effects might be particularly evident among older men. In a study of 407 men
between the ages of 50 and 91 years, which was published in the November
2002 issue of the Journal of Clinical Endocrinology and Metabolism, higher
free testosterone index values were associated with improved measures of
visual and verbal memory, visuospatial functioning, and the rate of decline
in visual memory. However, this research by Moffat and colleagues failed to
demonstrate an association between testosterone levels and measures of
verbal knowledge, mental status, or depressive symptoms.
The current study examines whether testosterone therapy could improve
neuropsychiatric and cognitive outcomes among a small cohort of older men
with or without AD.
Study Highlights
Patients eligible for study participation were men at least 50 years old who
scored at least a 15 on the Mini-Mental State Examination (MMSE). The
authors recruited matching cohorts of patients with and without AD. Patients
with a recent history of psychiatric illness, non-AD neurologic illness,
prostate disease, or substance abuse were excluded from study participation.
Study subjects were randomized to receive either 75 mg of testosterone 1%
gel applied daily or matching placebo. They were followed up for 24 weeks
for measures of cognition, neuropsychiatric functioning and levels of
depression, clinicians' global assessment of improvement, and quality of
life. Only subjects who completed the study protocol were analyzed for
outcomes.
The AD group comprised 18 men, while the non-AD cohort numbered 29. The
respective mean ages of subjects in the AD and non-AD groups were 70 and 62
years, and the mean scores on the baseline MMSE were 22 and 29.7,
respectively. The respective rates of hypogonadism at baseline were 28% and
21%. Baseline data between participants treated with testosterone vs placebo
were similar.
2 (22%) of 9 subjects in the testosterone-treated group with AD discontinued
the study, whereas 4 (29%) of 14 in the testosterone-treated group without
AD dropped out. There were more adverse events and study discontinuations
associated with testosterone therapy than placebo.
Serum testosterone levels significantly increased from baseline to week 24
in only 53% of subjects assigned to receive testosterone therapy. Among
subjects with AD, there were positive associations between changes in
testosterone levels and measures of visual recognition and quality of life.
There were no significant differences in cognitive outcomes between subjects
treated with placebo or testosterone in either the AD or non-AD cohorts.
However, subjects treated with placebo had a generally faster decline in
visual-motor integration than those treated with testosterone.
Neuropsychiatric and depression inventories were not improved with
testosterone therapy in either the AD or non-AD groups.
While testosterone therapy was not effective in improving the clinicians'
global assessment of change in the AD group, it was associated with an
improved quality-of-life score from caregivers when compared with placebo.
There was a trend toward improved self-reported quality of life among
participants in the non-AD group receiving testosterone vs placebo. Improved
quality of life associated with testosterone treatment was particularly
prominent after study week 12.
Pearls for Practice
Previous research indicates that higher values of the free testosterone
index were associated with improved measures of visual and verbal memory,
visuospatial functioning, and the rate of decline in visual memory among
older men. However, there was no significant association between
testosterone levels and measures of verbal knowledge, mental status, or
depressive symptoms.
Testosterone therapy may improve some quality-of-life measures among older
men with and without AD, but it appears to have minimal effects on
cognition, neuropsychiatric functioning, levels of depression, or global
assessment of improvement
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