Dioxin Alters Development of Male Reproductive System

DALLAS, Nov. 16 -- A dioxin in the Vietnam War-era herbicide Agent Orange affects the normal growth of the male reproductive system, according to researchers here.

Increased exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin -- or TCDD -- decreases the risk of benign prostatic hyperplasia and lowers testosterone levels, reported Amit Gupta, M.D., of the University of Texas Southwestern Medical Center in the November issue of Environmental Health Perspectives.

"Until now, we did not have very good evidence whether or not dioxins affect the human reproductive system," Dr. Gupta said. "Now we know that there is a link between dioxins and the human prostate."

On the other hand, he cautioned that reducing the risk of BPH through exposure to TDCC is probably not a good idea, because the compound is a known carcinogen.

"Several effective treatments are available for BPH," Dr. Gupta said, "and thus reduction of BPH by a toxic compound is not a desirable effect."

The finding comes from a prospective longitudinal cohort study, comparing Air Force veterans who were involved in the spraying the jungles of Vietnam with Agent Orange with age-matched veterans who were in Vietnam but not involved in the so-called Operation Ranch Hand.

The study has accumulated data on 971 Operation Ranch Hand and 1,266 comparison veterans, and more than 20 years of follow-up, including several detailed medical examinations, Dr. Gupta and colleagues reported.

TCDD is a byproduct of the production of one of the components of Agent Orange, so that exposure to the herbicide itself entailed exposure to TCDD, Dr. Gupta and colleagues noted.

The researchers divided the cohorts into quartiles, based on serum TCDD levels. Not surprisingly, the Operation Ranch Hand veterans had higher mean levels in each quartile.

Most dramatically, Operation Ranch Hand veterans in the highest quartile had a mean TCDD level of 76.16 parts per trillion, compared to a mean of 7.87 parts per trillion in the highest quartile of the comparison cohort.

Among the comparison cohort, the multivariate relative risk for benign prostatic hyperplasia was 0.84, with a 95% confidence interval from 0.73 to 0.98. There was a similar trend among the Operation Ranch Hand veterans, at least in the three lower quartiles, Dr. Gupta and colleagues said.

But the risk of the condition was higher in the highest TCDD quartile among those involved with spraying Agent Orange, compared with those in the lowest quartile. The relative risk of BPH was 1.35, with a 95% confidence interval from 1.05 to 1.74, which was statistically significant at P=0.02.

Over all the Operation Ranch Hand veterans, there was a trend toward an increased risk of BPH, but the risk was almost entirely for men with the highest exposure to TCDD, the researchers found.

"We found that the risk of developing BPH decreased with increasing exposure to dioxins in the comparison group," said study co-author Arnold Schecter, M.D., of the University of Texas School of Public Health Regional Campus in Dallas, and an authority on the effects of dioxins.

"The risk of developing BPH was 24% lower in the group with the highest dioxin levels compared to the group with the lowest levels," he said.

"In the Ranch Hand group, the risk of BPH tended to decrease with increased exposure to dioxins, but at extremely high exposure levels there was a tendency for the risk to increase," he added.

The BPH finding is not good news, Dr. Gupta said, even though the condition is associated with considerable morbidity.

"It may be construed that a decrease in the risk of BPH is not a harmful effect," he said, "but the larger picture is that dioxins are affecting the normal growth and development of the reproductive system."

In both groups, there was a consistent decrease in serum testosterone as levels of TCDD increased.

Lower testosterone levels are associated with decreased sexual function, decreased muscle mass and strength, infertility, increased fatigue, depression and reduced bone density, Dr. Gupta said.

But he said the researchers were unable to "conclude from this study that dioxin exposure did lead to any of these adverse affects in the veterans in the study."

The study was prospective and loss to follow-up was minimized, the researchers noted. On the other hand, the study only included data on TCDD and not on other dioxins and dioxin-like chemicals. Also, they said, the study population was predominantly white, so that the result may not generalize to other groups, and BPH was determined from medical records, which may have led to misclassification.