|
|
|
Testosterone: A Great Antidepressant! |
|
|
|
|
Written by Dave Palumbo
|
|
Tuesday, 11 March 2008 |
March 10, 2008 - Researchers have uncovered a link between low free
testosterone levels and depression. Their study, which appears in the March
issue of the Archives of General Psychiatry, shows that older men with
abnormally low free testosterone levels, or hypogonadism, were, on average, 271%
more likely to display clinically significant signs of depression than men with
higher testosterone levels.
"Importantly, these results could not be explained by increasing age,
education level, smoking, obesity or poor physical health - all factors that are
known to dampen testosterone and are associated with depression," said lead
author Osvaldo P. Almeida, MD, PhD, director of research, Western Australian
Centre for Health and Ageing, and professor and chair of geriatric psychiatry,
School of Psychiatry and Clinical Neurosciences, University of Western
Australia, Perth, Australia.
The results of this study could have important implications for the
treatment of depression in certain men, he said. "Older men with depression
should be assessed for hypogonadism, and older hypogonadal men who fail to
respond to standard antidepressant therapy may benefit from testosterone
replacement," said Dr. Almeida.
Results Independent of Physical Health
The study sample of 3987 men aged 71 to 89 years was taken from a community
sample of older male residents of Perth, Western Australia, who were part of the
larger prospective Health in Men Study.
To determine their physical health, the researchers used the weighted
Charlson index, which takes into account 17 common medical conditions including
myocardial infarction, congestive hart failure, peripheral arterial disease,
cerebrovascular disease, and chronic pulmonary disease. They retrieved linked
data for all participants from the Health in Men Study. As well, the
participants used the 36-Item Short Form Health Survey to rate their own
health.
The men were screened for cognitive impairment and depression, completing
the Standardized Mini-Mental State Examination and the 15-Item Geriatric
Depression Scale (GDS-15). In the sample, 203 (5.1%) had a total GDS-15 score
within the depression range (scores ≥ 7). Men with depression were older than
their counterparts without depression, had lower educational levels, and were
more likely to be former or current smokers and to have a body mass index (BMI)
of 30 kg/m2 or greater.
Researchers took blood samples to test serum concentrations of total and
free testosterone and divided the men into quintiles according to these
concentrations. Compared with men in the highest quintile, the odds ratio for
depression in men in the lowest quintile for total testosterone levels was 1.94.
However, the association between depression and total testosterone levels was
not significant after the analysis was adjusted for age, educational level,
smoking, BMI, and other factors.
Link With Free Testosterone Levels Remained Significant When
Adjusted
When the researchers looked at free testosterone levels, they found that
men in the lowest quintile also had an increased risk for depression in
relationship to men in the highest quintile (odds ratio, 3.12). However, this
association remained significant after the analysis was adjusted for age,
educational level, smoking, BMI, and other factors (odds ratio, 2.71).
"The findings of this study are compelling in suggesting a causal
relationship between low free testosterone and depression in older men," Dr.
Almeida told Medscape Psychiatry in an email. "The association is
biologically plausible; there is evidence from lab work that testosterone may
increase the bioavailability of serotonin and noradrenaline in the brain and
this could explain its antidepressogenic effect."
Current evidence suggests that free testosterone, or testosterone that is
not bound to the proteins albumin and sex hormone-binding globulin, is
biologically active (also called bioavailable testosterone). "In other
words, if we wish to clarify what testosterone does, we need to look at free
testosterone," said Dr. Almeida.
Twenty Percent of Men Older Than 70 Years Develop Hypogonadism
The study results do not mean that all older men should receive
testosterone replacement therapy, but they do suggest that this therapy should
be considered for the significant number of older men with low male hormone
levels, said Dr. Almeida. "The association between depression and free
testosterone is limited to hypogonadal men or men with abnormally low free
testosterone," he added. "After age 70 years, approximately 20% of men develop
hypogonadism. This particular group may benefit from testosterone
replacement."
Dr. Almeida added that randomized trials are now needed to determine if
testosterone replacement is effective and safe to treat depression in this
group.
He stressed that the association between free testosterone levels and
depression is a "risk" association rather than a cause-consequence effect. "Not
all older men with depression are hypogonadal, and not all hypogonadal men have
depression. But there is a dramatic increase in the risk of depression among
hypogonadal men."
As the population ages, there is likely to be an increase in the number of
men with hypogonadism, said Dr. Almeida.
He noted, too, that although depression is more prevalent among women, the
gap between the sexes "all but disappears" later in life. "Our findings may
partly explain why that is so," he said.
The study was supported by grants from the National Health and Medical
Research Council of Australia. Biochemical analyses were funded by a Sylvia and
Charles Viertel Charitable Foundation Clinical Investigator Award. The study
authors have disclosed no relevant financial relationships.
Arch Gen Psychiatry. 2008;65:283-289.
Clinical Context
Depression is a leading cause of disability worldwide, affecting 2% to 5%
of the population. The prevalence of depression in women is higher vs men
throughout the lifespan, but sex differences disappear after the age of 65
years. Serum concentrations of gonadal hormones have been associated with
various measures of well-being. In men, relative androgen deficiency in later
life has been linked to decreased lean mass and increased fat mass, osteopenia,
decreased muscle strength, fatigue, decreased hematocrit values, systemic
illness, increased risk for coronary heart disease, and poor concentration. It
has been postulated that the association of low testosterone concentrations and
mood is confounded by concurrent physical morbidity.
The aim of this study was to determine whether the association between
serum testosterone concentrations and mood in older men is independent of
physical comorbidity.
|
|
Research and Review 