Birth defects in children of men exposed in utero to diethylstilbestrol (DES).

OBJECTIVE: Prenatal exposure to diethylstilbestrol (DES) is associated with adverse effects, including genital anomalies and cancers in men and women. Animal studies showed birth defects and tumors in the offspring of mice prenatally exposed to DES. In humans, birth defects, such as hypospadias were observed in children of prenatally exposed women. The aim of this research was to assess the birth defects in children of prenatally exposed men. METHODS: In a retrospective study conceived by a patients' association (Réseau DES France), the reports of men prenatally exposed to DES on adverse health effects in their children were compared with those of unexposed controls and general population. RESULTS: An increased incidence of two genital anomalies, cryptorchidism (OR=5.72; 95% CI 1.51-21.71), and hypoplasia of the penis (OR=22.92; 95% CI 3.81-137.90), was observed in the 209 sons of prenatally exposed men compared with controls, but hypospadias incidence was not increased in comparison with either the controls or the general population. No increase of genital anomalies was observed in daughters. CONCLUSION: With caution due to the methods and to the small numbers of defects observed, this work suggests an increased incidence of two male genital tract defects in sons of men prenatally exposed to DES. This transgenerational effect, already observed in animals and in the offspring of women prenatally exposed to DES, could be the result of epigenetic changes transmitted to the subsequent generation through men.

Adverse health effects in children of women exposed in utero to diethylstilbestrol (DES).

OBJECTIVE: Exposure to diethylstilbestrol (DES) in utero is associated with adverse health effects, including genital anomalies in women and men, and cancers in women. Animal studies showed birth defects and tumors in the offspring of DES exposed mice, revealing transgenerational transmission of DES effects. In humans, birth defects, such as hypospadias were observed in children of prenatally exposed women. The aim of this research was to further assess the health effects in children of prenatally exposed women. METHODS: In a retrospective cohort study, the reports of women exposed to DES in utero on their 4409 children were compared with those of unexposed women on their 6203 children. Comparisons used odd ratios (OR) between children of exposed and unexposed women and standardized incidence rate (SIR) with the general population. These cohorts were recruited on a voluntary basis to answer questionnaires. RESULTS: There was a global increase of defects in children born to exposed women when compared with those born to unexposed (OR 2.29, 95% CI: 1.80-2.79, P<0.001) and with the general population (SIR 2.39, 95% CI: 2.11-2.68). Increased defects were observed in male genital tract, esophagus, lip or palate, musculoskeletal and circulatory systems. For female genital tract anomalies, there was no significant increase. However, this cohort being relatively young, further follow-up is needed. An increase of cerebral palsy was revealed. The incidence of cancers was not increased, in particular for breast, uterus and ovary. CONCLUSION: Our results confirmed a transgenerational transmission of defects in male genital tract. With caution due to possible bias associated with this method, our data suggest an increase of defects for esophagus, lip or palate, musculoskeletal and circulatory system in children of exposed women.

Cancer Risk in Women Exposed to Diethylstilbestrol in Utero.

OBJECTIVE: To evaluate the overall cancer risk, primarily breast cancer, for women exposed to diethylstilbestrol (DES) in utero in France. METHODS: A cohort of 3 436 prenatally DES exposed women and a comparable cohort of 3256 unexposed women were recruited retrospectively from voluntary responses to questionnaires, and cases were ascertained by medical history at the time of recruitment. RESULTS: One hundred ninety-five cancers were observed in exposed women (136 breast cancers, and 59 in other sites) and 141 cancers in unexposed women (90 breast cancers, and 51 others). A significant increase of breast cancers was found in exposed women, with a multivariate incidence rate ratio of 2.10 (95% CI 1.60-2.76) when compared with unexposed women. When exposed women were compared with the general population in France, the standardized incidence ratio was 2.33 (95% CI 1.93-2.72). CONCLUSION: Our results suggest a significant increase of breast cancer in prenatally DES exposed women when compared with unexposed women and with the general population. For other cancers, except clear cell carcinoma of the cervix or vagina, there was a global non-significant increase.