[Pharmwaste] A population-level decline in serum testosterone levels in American men.

[DeBiasi,Deborah]

http://www.ourstolenfuture.org/NewScience/reproduction/2006/2006-1210tra
visonetal.html

Travison, TG, AB Araujo, AB O'Donnell, V Kupelian, JB McKinlay. 2007. A
population-level decline in serum testosterone levels in American men.
Journal of Clinical Endocrinology and Metabolism 92:196-202.


In one of the largest study of its kind, Travison et al. report a
population-wide decline in Massachusetts's men's testosterone levels
during the last 20 years that is not related to normal aging or to
health and lifestyle factors known to influence testosterone levels. 

They found that testosterone concentrations dropped about 1.2% per year,
or about 17% overall, from 1987 to 2004. The downward trend was seen in
both the population and in individuals over time. 

The decline is consistent with other long-term trends in male
reproductive health, including decreases in sperm quality and increases
in testicular cancer, hypospadias and cryptorchidism. 

The strongest association was observed in same-aged men from different
sampling years. For example, a 65-year-old in 2002 had lower
testosterone levels than a 65-year-old in 1987. 

Lower concentrations of testosterone can increase a man's risk for
age-related diseases, depression and infertility.
 
Also, the younger and older men in the study experienced similar hormone
declines that dropped faster than would be predicted by normal aging. 

Context: In men, the hormone testosterone guides behavior and
reproduction. It controls growth and development of sex organs and other
typically male characteristics, such as facial hair and a deep voice. 

Normally, levels fluctuate from conception through puberty then level
out during adulthood before declining as men age. Some chronic health
problems typically seen in older adults, such as diabetes, depression
and obesity, are associated with lower testosterone levels.

Recent studies have that found environmental impacts on testosterone
levels. For example, testosterone levels were lower in US Air Force
veterans exposed to dioxins while spraying Agent Orange during the
Vietnam War, as well as in men exposed to phthalates at work. 

What did they do?

Travison et al. used blood hormone data and personal information
collected from men living in Boston, MA, as part of the Massachusetts
Male Aging Study (MMAS). The MMAS examined men's health and endocrine
function. Data were gathered during three home visits from 1987-89 (T1),
1995-97 (T2), and 2002-04 (T3). Total testosterone (TT) and serum sex
hormone-binding globulin were measured in the blood and available
testosterone (BT) was calculated. The men self-reported such things as
basic demographics, health status, and smoking and alcohol use. 

In this study, Travison et al. analyzed data from 1,532 men (1,383, 955,
and 568, respectively, from T1, T2 and T3) that met age and birth year
requirements. Participants ranged from 45 to 79 years old and were born
between 1916 and 1945. The researchers excluded high and low T levels,
missing data, and unidentified prostate cancer treatment. Within the
sample, they calculated and compared three separate but related
associations among concentration, age, and time. They looked at changes
in testosterone concentrations in the group of men at different years
and ages associated with T1, T2, and T3; testosterone declines in
individual men as they aged during the study; and testosterone
concentrations of men of the same age but in different years
(age-matched). 

What did they find?

Travison et al. found strong evidence of a decline of more than 1% per
year in men's blood testosterone levels during the last two decades. The
graph to the right shows average levels for each for men of different
ages in each of the three measurement periods (T1-T3).

Dotted lines are 95% confidence bands. Adapted from Travison et al. 
The first comparison to make is that within a cohort, older men tend to
have lower testosterone levels. Compare, for example, 80 yr old men in
T3 compared to 60 yr old men.

The crucial comparison to make is from one cohort to the next, comparing
men of the same age. For example, 60 yr old men during the first
measurement period (red line, 1987-1989) had total testosterone levels
over 500 ng/dL. Men aged 60 yrs old in the third cohort (blue line,
measured 2002-2004) had TT below 450 ng/dL. There is no overlap between
the confidence bands of T1 vs T3: T3 (measured 2002-2004) is always
lower than T1.

The trend holds regardless of the men's age. Similar declines over the
17 years were seen in all ages of men in the study. 

Travison et al. note that the decline within the cohorts related to age
is less than the decrease observed across cohorts. For example, men aged
70 in T1 had TT only 6% less than men aged 45 in the same cohort. But 60
yr old men in T3 had TT concentration approximately 13% lower than men
the same age in T1. 

To illustrate this point another way, Travison et al. compared the
average decline of testosterone levels in T1 vs T2 as a function of age,
and then contrast that with differences in testosterone between men of
the same age in T1 vs T2. Note that T1 and T2 were only separated by 9
years. The average declines in T1 and T2 per decade of life were 17 and
20 ng/mL, respectively. But 65 yr old men in T2 had total testosterone
levels 50 ng/mL lower than those in T1, even though the samples were
separated by less than a decade.

Travison et al. then estimated the decline over time, from the first
cohort to the third, for men of the same age (what they called the
age-matched decline). They found that testosterone declined by 1.2% per
year (95% CI 1.0% to 1.4%). 

Bioavailable testosterone (BT) also showed similar declines over time.
The strongest associations again held for age-matched trends with
declines of 1.3% per year (95% CI 1.7% - 1.1%).

None of the health and lifestyle factors examined were associated with
either age-matched declines in either TT or BT: The age-matched declines
remained essentially the same after controlling for chronic illness,
general health, medications, smoking, body mass index, employment,
marital status, and other indicators. 

Finally, the trends held when analyzing the data in a number of
different ways, including by interview date, study cohort, restricting
to men of certain ages or birth cohorts, and considering incomplete
versus complete data.

What does it mean?

Travison et al. find that testosterone levels declined in Massachusetts
men by approximately 1.2% per year from the late 1980s through 2004,
controlling for the age of the men and other possible confounding
variables. 

This study is important because of its large sample size and long
duration. Few studies have looked directly at testosterone levels over
time. 

The results are surprisingly consistent with another set of long-term
human epidemiology studies. Those studies also show a long-term decline
in male reproductive functions, such as decreased sperm health and
increased infertility, which are highly associated with or controlled by
testosterone and other androgen hormones. The rate of decline reported
in this study is roughly comparable to the rate of decline of sperm
count reported first by Carlson et al. in 1992 and then reanalyzed by
Swan et al.in 2000. 

In commentary accompanying Travison et al.'s study in the Journal of
Clinical Endocrinology and Metabolism, Dr. Shalender Bhasin (Boston
Medical Center) writes: The data in this study are "important because
they provide independent support for the concerns raised earlier about
the reproductive health of men." ... "it would be unwise to dismiss
these reports as mere statistical aberrations because of the potential
threat these trends-- if confirmed-- pose to the survival of the human
race and other living residents of our planet." 



Deborah L. DeBiasi
Email:   dldebiasi at deq.virginia.gov
WEB site address:  www.deq.virginia.gov
Virginia Department of Environmental Quality
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