Male Infertility Right Up There with Smoking,
Diabetes as Death Risk
Stanford study finds two abnormalities in semen
equals doubled mortality risk in 8 years
May 16, 2014 – Most of us are aware that smoking
and diabetes double our risk of death. Now, you can add a third to this
deadly list – defective semen. Men with two or more abnormalities in
their semen were more than twice as likely to die over a roughly
eight-year period as men who had normal semen, the study found.
Smoking and diabetes — either of which doubles
mortality risk — both get a lot of attention, noted the study's lead
author, Michael Eisenberg, MD, PhD, assistant professor of urology and
director of male reproductive medicine and surgery at Stanford
University School of Medicine.
"But here we're seeing the same doubled risk with
male infertility, which is relatively understudied."
Infertility is a widespread medical complaint in
developed countries, where about one in seven couples is affected at
some point. But this is only the third study worldwide, and the first in
the United States, to address the question of a connection between male
infertility and mortality, said Eisenberg.
Results from the two earlier studies, one in
postwar Germany and another of more recent vintage in Denmark, were
In the new study titled "Semen quality, infertility
and mortality in the USA," to be published online May 16 in Human
Reproduction, Eisenberg and his colleagues examined records of men
ages 20 to 50 who had visited one of two centers to be evaluated for
In all, about 12,000 men fitting this description
were seen between 1994 and 2011 at Stanford Hospital & Clinics or
between 1989 and 2009 at the Baylor College of Medicine in Houston. At
both clinics, data were available for several aspects of a patient's
semen quality, such as total semen volume and sperm counts, motility and
shape. (Dolores Lamb, PhD, and Larry Lipshultz, MD, of Baylor were
senior authors of the study.)
By keying identifiers for the patients to data in
the National Death Index and the Social Security Death index, the
investigators were able to monitor these men's mortality for a median of
about eight years.
"We were able to determine with better than 90
percent accuracy who died during that follow-up time," Eisenberg said.
"There was an inverse relationship. In the years following their
evaluation, men with poor semen quality had more than double the
mortality rate of those who didn't."
While no single semen abnormality in itself
predicted mortality, men with two or more such abnormalities had more
than double the risk of death over the eight-year period following their
initial fertility examination compared with those with no semen
abnormalities. The greater the number of abnormalities, the higher the
mortality rate, the study found.
"Eisenberg and colleagues provide empirical
evidence in support of the evolving literature suggesting that human
fecundity influences health and disease across the life span," Germaine
Buck Louis, PhD, director of the division of intramural population
health research at the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, wrote in an accompanying editorial,
"Male fecundity and its implications of health and
disease across the lifespan," in Human Reproduction. "Human fecundity
may be both informative and predictive about continual health status and
Of the 11,935 men who were followed, 69 died during
the follow-up period — a seemingly small number. This reflects, first
and foremost, the patients' relative youth: Their median age was 36.6
years. But it also reflects the fact that men who get evaluated for
infertility tend to have a higher-than-average socio-economic status and
have accordingly better diets, education and access to health care.
Moreover, men who are concerned about infertility
are men who want to have children. "If you're trying to have a child,
you're probably reasonably healthy at the moment and in mental shape to
be planning for your future," Eisenberg said. In fact, the men seen at
the two medical centers — both those with and those without semen
abnormalities — tended to die at slower rates than the general U.S. male
Nevertheless, within this select group, the
difference in death rates between those who had semen abnormalities and
those who didn't was statistically significant. Those with two or more
semen abnormalities were more than twice as likely to die during the
follow-up period as those without any. This difference remained despite
the investigators' efforts to control, where possible, for baseline
health differences between the two sets of patients. They corrected for
age and known diseases.
"It's plausible that, even though we didn't detect
it, infertility may be caused by pre-existing general health problems,"
Eisenberg said. The true cause of increased mortality risk, then, would
be not infertility per se, but those health problems.
"But we controlled for this factor as best we
could, and while that did attenuate the measured risk somewhat, there
seems to be something else going on. Could it be genetic, developmental
or hormonal factors? Or could it be that something about the experience
of having and raising kids — even though you may sometimes feel like
they're killing you — actually lowers mortality?"
Eisenberg and his associates are trying to figure
out why this is happening. "Is their blood pressure rising? What about
their blood sugar, or other measures? We are starting to do prospective
data collections now, through a collaboration involving several centers
in the United States and Canada," he said.
Other Stanford co-authors of the study were Barry
Behr, PhD, professor of obstetrics and gynecology; Mark Cullen, MD,
professor of medicine; and Shufeng Li, a statistical programmer.
Researchers from Baylor and Yale University also contributed to the
study, which was funded by the National Institutes of Health (grants
P01HD36289 and UL1 RR025744).
The Stanford University School of Medicine reports
it consistently ranks among the nation's top medical schools,
integrating research, medical education, patient care and community
service. For more news about the school, please visit
The medical school is part of Stanford Medicine, which includes Stanford
Hospital & Clinics and Lucile Packard Children's Hospital Stanford. For
information about all three, please visit
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