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Amit Gupta,^1,2 Norma Ketchum,³ Claus G. Roehrborn,¹ Arnold Schecter,² Corinne C. Aragaki,² and Joel E. Michalek⁴

¹Department of Urology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA; ²The University of Texas School of Public Health, Regional Campus at Dallas, Dallas, Texas, USA; ³Air Force Research Laboratory, Brooks City-Base, Texas, USA; ⁴Center for Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Abstract

Background: Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange, during the Vietnam War in 1962–1971 ; Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) . It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias.

Objectives: In this study, our objective was to assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels.

Methods: This study was a longitudinal, prospective cohort study made up of U.S. Air Force veterans involved in Operation Ranch Hand. Other Air Force veterans who did not spray herbicides were included as comparisons. BPH was determined by medical record review and by medical examinations conducted during the study. Data were available for 971 Ranch Hand and 1,266 comparison veterans. We investigated the relationship between BPH and serum TCDD level using the Cox proportional hazards models adjusted for testosterone levels, body mass index (BMI) , and the percentage change in BMI per year.

Results: In univariate and multivariate analyses, the risk of BPH decreased with increasing serum TCDD in the comparison group. The multivariate risk ratio for BPH in the comparison group was 0.84 (95% confidence interval, 0.73–0.98) . Excluding men with prostate cancer, inflammatory or other prostatic diseases did not substantially alter the association. Serum testosterone levels were inversely associated with serum TCDD levels in both Ranch Hand and comparison groups.

Conclusions: TCDD exposure at general population levels is associated with a decreasing risk of BPH with higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels.

Key words: benign prostatic hyperplasia, BPH, dioxins, endocrine disruptors, persistent organic pollutants, Ranch Hand, testosterone, TCDD, Vietnam veterans. Environ Health Perspect 114:1649–1654 (2006) . doi:10.1289/ehp.8957 available via http://dx.doi.org/ [Online 20 July 2006]

Address correspondence to A. Gupta, Department of Urology, University of Texas Southwestern Medical Center at Dallas, J8.130, 5323 Harry Hines Blvd., Dallas, TX 75390-9110 USA. Telephone: (972) 900-0362. Fax: (214) 648-8786. E-mail: amit.gupta@utsouthwestern.edu

We thank all of the veterans who participated in the Air Force Health Study.

This study was supported by the U.S. Air Force under contract 276700F1.

The authors declare they have no competing financial interests.

Received 25 December 2005 ; accepted 20 July 2006.

Correction

In the original manuscript published online, “BMI at the start of the Southeast Asia tour” was incorrect. It has been corrected here (in the text and in Tables 1, 4, and 5) . “BMI_tour” is now defined as the BMI at the end of the Southeast Asia tour. Veterans were excluded from the study if the BMI was not available for the end of the Southeast Asia tour.