Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study

Julie R Palmer; Arthur L Herbst; Kenneth L Noller; Deborah A Boggs; Rebecca Troisi; Linda Titus-Ernstoff; Elizabeth E Hatch; Lauren A Wise; William C Strohsnitter; Robert N Hoover

doi:10.1186/1476-069x-8-37

Lifestyle and Environment · Environmental Exposures

Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study

Palmer JR, Herbst AL, Noller KL, Boggs DA, Troisi R, Titus-Ernstoff L, Hatch EE, Wise LA, Strohsnitter WC, Hoover RN

Published August 18, 2009 Environmental health : a global access science source

DOI 10.1186/1476-069x-8-37 PMID 19689815 PMC PMC2739506

RRM Academy Synopsis

Sons exposed to DES before birth reported more undescended testes

A cohort study of three U.S. groups found that sons exposed to DES before birth reported more undescended testes and epididymal cysts. DES, or diethylstilbestrol, is a synthetic estrogen once prescribed in pregnancy. The associations were strongest when exposure began before week 11 of pregnancy.

Key Findings

Researchers combined three U.S. cohorts and mailed questionnaires to 3067 eligible men (1638 exposed, 1429 unexposed). Responses came from 71 percent of exposed and 69 percent of unexposed men.
Prenatal DES exposure was associated with cryptorchidism (risk ratio 1.9, 95% CI 1.1-3.4) and epididymal cyst (risk ratio 2.5, 95% CI 1.5-4.3).
Before the 11th week, exposure carried a risk ratio of 3.5 (2.0-6.0) for epididymal cyst, 2.9 (1.6-5.2) for cryptorchidism, and 3.0 (1.7-5.4) for testicular inflammation/infection.
When exposure began after the 11th week, the risk ratio for cryptorchidism was 1.1 (0.5-2.5).
No association appeared with varicocele, urethral stenosis, structural penile abnormalities, benign prostatic hypertrophy, or inflammation or infection of the prostate, urethra, and epididymis.

Interpretation

This cohort study combined three U.S. groups of men whose mothers' DES exposure was documented in medical records. For cryptorchidism, epididymal cyst, and testicular inflammation, the associations grew stronger with earlier and higher exposure. The authors link earlier conflicting results to differences in timing and dose among cohorts. The authors note that the men reported their own outcomes. The findings support further study of prenatal exposure timing and male urogenital outcomes.

RRM Context

Restorative reproductive medicine looks for what lies behind a reproductive problem in both partners. DES, a synthetic estrogen given to pregnant women, was followed by reproductive abnormalities in their children. The authors tie their findings to a hypothesis about endocrine disrupting chemicals and rising cryptorchidism. A root-cause view of a man's health reaches back to his time in the womb.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters. Studies of prenatally-exposed males have yielded conflicting results.

Methods

In data from a collaborative follow-up of three U.S. cohorts of DES-exposed sons, we examined the relation of prenatal DES exposure to occurrence of male urogenital abnormalities. Exposure status was determined through review of prenatal records. Mailed questionnaires (1994, 1997, 2001) asked about specified abnormalities of the urogenital tract. Risk ratios (RR) were estimated by Cox regression with constant time at risk and control for year of birth.

Results

Prenatal DES exposure was not associated with varicocele, structural abnormalities of the penis, urethral stenosis, benign prostatic hypertrophy, or inflammation/infection of the prostate, urethra, or epididymus. However, RRs were 1.9 (95% confidence interval 1.13.4) for cryptorchidism, 2.5 (1.54.3) for epididymal cyst, and 2.4 (1.54.4) for testicular inflammation/infection. Stronger associations were observed for DES exposure that began before the 11th week of pregnancy: RRs were 2.9 (1.65.2) for cryptorchidism, 3.5 (2.06.0) for epididymal cyst, and 3.0 (1.75.4) for inflammation/infection of testes.

Conclusion

These results indicate that prenatal exposure to DES increases risk of male urogenital abnormalities and that the association is strongest for exposure that occurs early in gestation. The findings support the hypothesis that endocrine disrupting chemicals may be a cause of the increased prevalence of cryptorchidism that has been seen in recent years.

Topics

Lifestyle and Environment Environmental Exposures Endocrine Disrupting Chemicals

Lifestyle and Environment › Environmental Exposures › Endocrine Disrupting Chemicals

Julie R Palmer, Arthur L Herbst, Kenneth L Noller, Deborah A Boggs, Rebecca Troisi, Linda Titus-Ernstoff, Elizabeth E Hatch, Lauren A Wise, William C Strohsnitter, Robert N Hoover

J Palmer, A Herbst, Ken Noller, K Noller, Debbie Boggs, Deb Boggs, D Boggs, Becky Troisi, R Troisi, L Titus-Ernstoff, Liz Hatch, Beth Hatch, Betsy Hatch, E Hatch, L Wise, Bill Strohsnitter, Will Strohsnitter, Billy Strohsnitter, W Strohsnitter, Bob Hoover, Rob Hoover, Bobby Hoover, R Hoover

PMID 19689815 19689815 DOI 10.1186/1476-069x-8-37 10.1186/1476-069x-8-37 Palmer et al. 2009, Palmer 2009

Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study

Sons exposed to DES before birth reported more undescended testes

Key Findings

Interpretation

RRM Context

Abstract

Topics

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