November 15, 2006 — A dioxin in the herbicide Agent Orange damages male reproductive health by lowering testosterone levels, researchers at UT Southwestern Medical Center have found in a cohort study of more than 2,000 Air Force veterans who served during the Vietnam War.

Exposure to this Agent Orange dioxin, called TCDD, also reduces growth of the prostate gland, the study found. Older men heavily exposed to Agent Orange may have smaller prostates and less tendency to develop BPH.

Published in the November issue of the journalEnvironmental Health Perspectives, the study indicates that exposure to TCDD, the most toxic dioxin contained in Agent Orange, may disrupt the male endocrine and reproductive systems in several ways.

An earlier study found that even Vietnam veterans who were not involved in spraying Agent Orange experience higher levels of dioxin contamination, which is linked to an increased overall risk of cancer (see sidebar below)

In 1996, acting on a recommendation from the U.S. Veterans' Affairs Department, President Bill Clinton added prostate cancer and peripheral neuropathy (nerve damage) to a list of seven diseases for which Agent Orange victims can receive disability payments. Clinton,according to CNN, said the nation must "never stop trying" to help Vietnam veterans "damaged" by Agent Orange. At that time the National Academy of Sciences reconfirmed a limited association between Agent Orange and prostate cancer. Academy scientists also raised the possibility of a link between the herbicide and spina bifida. But the VA has never admitted any such links.

In 2005 a group of U.S. Air Force and other researchers analyzed cancer rates among nearly 1,500 Air Force veterans who served in Southeast Asia during the Vietnam War, but did not actually spray Agent Orange or other herbicides. The men served as a comparison group in a previous study of cancer risk in veterans of Operation Ranch Hand, the unit responsible for spraying Agent Orange. Even though they didn't work with Agent Orange, veterans in the comparison group had significant blood levels of TCDD, the highly toxic dioxin contaminant of Agent Orange.

Now the current study has found that TCDD lowers levels of the male hormone testosterone slows the growth of the prostate gland.

"Until now, we did not have very good evidence whether or not dioxins affect the human reproductive system," said Dr. Amit Gupta, a urologist at UT Southwestern and the study's lead author. "Now we know that there is a link between dioxins and the human prostate leading us to speculate that dioxins might be decreasing the growth of the prostate in humans like they do in animals."

Almost 20 million gallons of herbicides were dumped on Vietnam between 1962 and 1971 to kill jungle foliage with the aim of exposing enemy targets.  Shortly following their military service in Vietnam, some veterans reported a variety of health problems and concerns which some of them attributed to exposure to Agent Orange or other herbicides.

Dr. Gupta's team of researchers found that veterans exposed to dioxin had lower rates of benign prostate hyperplasia (BPH), better known as enlarged-prostate disease. BPH is a disease in humans that is caused by an enlargement of the prostate. Patients must strain to pass urine and they also must urinate frequently. BPH can lead to complications such as an inability to urinate and urinary tract infection. Surgery is sometimes needed.

Dr. Claus Roehrborn, professor and chairman of urology at UT Southwestern and a study author, said, "We know that dioxin causes many endocrine disturbances in the human body. The study indirectly proves that BPH is an endocrine disorder."

Dr. Gupta cautioned that decreased risk for BPH found in the veterans groups should not be interpreted as a positive result.

"It may be construed that a decrease in the risk of BPH is not a harmful effect, but the larger picture is that dioxins are affecting the normal growth and development of the reproductive system. Moreover, several effective treatments are available for BPH and thus reduction of BPH by a toxic compound is not a desirable effect."

The study was based on data from the Air Force Health Study (AFHS). The AFHS is an epidemiologic study of more than 2,000 Air Force veterans who were responsible for spraying herbicides including Agent Orange during the Vietnam War. This group is called the Ranch Hand group because the spray program was called Operation Ranch Hand. Agent Orange was contaminated by a dioxin called 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD).

The veterans were interviewed and underwent physical examinations and lab tests during six examination cycles. The first cycle was conducted in 1982, so the veterans were followed for more than 20 years.

"We found that the risk of developing BPH decreased with increasing exposure to dioxins in the comparison group," said Dr. Arnold Schecter, professor of environmental sciences at the UT School of Public Health Regional Campus at Dallas and a study author. "The risk of developing BPH was 24 percent lower in the group with the highest dioxin levels compared to the group with the lowest levels. 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."

In addition, the study shows that higher dioxin exposure is associated with decreased testosterone levels, Dr. Gupta said.

"It is known that 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. "However, we could not conclude from this study that dioxin exposure did lead to any of these adverse affects in the veterans in the study."

Most of the study participants were whites, so, the researchers say, " the results may not be generalized to the entire population." In addition, "BPH was determined by use of medical records, which may result in some misclassification."

The study points out the necessity to conduct additional environmental studies of the impact of dioxins and other toxins on the male reproductive system. Previous research was largely based on animal models, Dr. Gupta said, noting that the urgency of further research is underlined by a rise in disorders of the male reproductive tract over the past several decades.

These include a decrease in sperm production by almost 50 percent, a three- to four-fold increase in testicular cancer, an increase in the incidence of cryptorchidism (undescended testes, a condition where the testes are not in their normal location in the scrotum) and hypospadias (abnormality of the urethra).

The reason for this increase is not known, but it is thought that these disorders might be caused by environmental chemicals that are estrogenic and have endocrine-disrupting effects, Dr. Gupta said.

Dioxins are among the most toxic substances known and are thought to be partially responsible for this increase in male reproductive tract disorders. They are formed as byproducts of processes such as incineration, smelting, paper and pulp manufacturing as well as pesticide and herbicide production.

Humans are exposed to these chemicals primarily through consumption of animal fat and dairy products. Babies are exposed to the highest levels of dioxins through breast milk. Dioxins are eliminated extremely slowly from the body and they tend to stay in the body for several years to several decades after exposure.

Researchers contributing to the study came from UT Southwestern Medical Center, UT Health Science Center at San Antonio and the Air Force Research Laboratory, Brooks City-Base, Texas.

Read the research article:

Serum Dioxin, Testosterone, and Subsequent Risk of Benign Prostatic Hyperplasia: A Prospective Cohort Study of Air Force VeteransAmit Gupta, et al.Environmental Health Perspectives Volume 114, Number 11, November 2006