Prescribing
testosterone to relatively healthy older men with low or low to normal
testosterone levels does not improve cognitive function and is not justified,
new research suggests.
"Testosterone
administration for 3 years to raise testosterone concentrations into a range
that is mid-normal for healthy young men was not associated with improvement in
any domain of cognitive function," Grace Huang, MD, of Brigham and Women's
Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues
report.
The results
are from a prespecified secondary analysis of data from the Testosterone
Effects on Atherosclerosis in Aging Men (TEAAM) trial and were published online
July 1 in the Lancet Diabetes and Endocrinology.
The
original results from the TEAAM trial showed no significant rate of change in
common carotid artery intima-media thickness or coronary artery calcium levels
(coprimary outcomes), overall sexual function, or health-related quality of
life in the testosterone group in comparison with the placebo group.
The
prespecified analysis of cognitive function included 280 men aged 60 years and
older with low or low to normal testosterone concentrations (3.47 to 13.9
nmol/L, or free testosterone < 173 pmol/L) and normal cognitive function who
were randomly allocated to receive either 7.5 g of 1% testosterone gel or
placebo gel for 3 years. The testosterone dose was adjusted to achieve
concentrations of 17.3 to 31.2 nmol/L. Men receiving testosterone experienced
androgenic effects consistent with overall compliance with daily testosterone
gel application.
In men
using testosterone gel, mean serum concentrations of total testosterone rose
from 10.6 nmol/L to 19.7 nmol/L, and free testosterone concentrations increased
from 222 pmol/L to 364 pmol/L. In contrast, men receiving placebo gel had no
marked increase in serum total testosterone concentrations (10.7 nmol/L at
baseline vs 11.1 nmol/L post intervention) or free testosterone concentraitons
(210 pmol/L to 364 pmol/L).
Performance
on a broad range of domains of cognitive function did not differ significantly
between groups at any time point, after adjusting for age, education, and
baseline cognitive function, the researchers report. In both the
intention-to-treat and per-protocol populations, changes in cognitive function
scores were not related significantly to changes in total or free testosterone
concentrations or estradiol concentrations, they note.
"With
an intervention duration of 3 years, our trial is one of the longest and
largest randomized placebo-controlled trials so far of testosterone in older
men," the authors say. Unlike other studies, multiple domains of cognitive
function, including visuospatial ability, verbal memory, verbal fluency,
attention, executive function, and manual dexterity, were assessed using a
comprehensive battery of standardized neuropsychological tests, including
measures known to be sensitive to gonadal steroids.
The data,
the authors conclude, "do not support use of testosterone for improvement
in cognitive function in older men with age-related decline in testosterone
concentrations."
"These
negative findings are the best evidence so far regarding the effect of
testosterone treatment on cognition in asymptomatic, fairly healthy older men
with low testosterone," write Bradley Anawalt, MD, and Stephanie Page, MD,
PhD, of the University of Washington, Seattle, in a linked commentary.
"For older men with clinically normal cognitive function, low to
low-to-normal serum total testosterone concentrations, and no known cause for hypogonadism,
testosterone treatment is not an elixir for the brain," they say.
In an
interview with Medscape Medical News, Dr Page said the findings are not
surprising given the characteristics of the men who were included in the study.
"They
were highly educated and didn't have any cognitive dysfunction. This tells us
is that if you supplement men with testosterone that are healthy otherwise, at
least in terms of their cognitive function, that there aren't gains to be
had," she said.
Dr Page
also noted that "many men are being prescribed testosterone without
adequate screening, for sort of unclear reasons. I think there is a notion out
there that testosterone can be a panacea for a number of age-associated
declines, and I think what this [study] tells us is that while testosterone may
have some significant benefits for some individuals, it's not a panacea."
Several
important clinical questions regarding testosterone and cognitive function were
not addressed by this study, Dr Anawalt and Dr Page write in their commentary.
"First,
what are the cognitive effects of testosterone treatment for men with known
causes of hypogonadism, such as Klinefelter syndrome; second, does long-term
testosterone treatment prevent cognitive impairment, decline, or dementia in
young and middle-aged men with low serum testosterone concentrations; and
third, what effects of testosterone are mediated via androgen effects and what
are mediated via its metabolite, oestradiol?"
The study was supported by a grant from Solvay
Pharmaceuticals and by AbbVie Pharmaceuticals (after AbbVie acquired the
Androgel brand from Solvay Pharmaceuticals). Testosterone and placebo gels for
the study were provided by Solvay Pharmaceuticals and later by AbbVie
Pharmaceuticals. One investigator has received research grant support from
AbbVie. Dr Page has disclosed no relevant financial relationships.
Lancet
Diab Endocrinol.
Published online July 1, 2016. Abstract, Commentary
Megan
Brooks
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