Confirmed Health Effects of DES Exposure
There are few known health effects of in utero DES exposure for men. There have been only a few studies, and they have produced conflicting results.
Non-neoplastic Genital Abnormalities
Non-neoplastic changes have been described in men exposed to DES in utero (Bibbo et al., 1977; Conley et al., 1983; Gill et al., 1979; Leary et al., 1984; Niculescu, 1985; Vessey et al., 1983; Wilcox et al., 1995). The most common health effect for DES sons is the occurrence of benign epididymal cysts. The likelihood of DES sons having epididymal cysts ranges from 21% to 30%, in comparison with 5% to 8% of unexposed men (Gill, 1988; Gill et al., 1979).
It is unclear whether there are higher rates of other abnormalities—cryptorchidism, hypospadias, and microphallus—among DES sons. Gill and colleagues (1979), and Wilcox and colleagues (1995), estimated that about 15% to 30% of men exposed to DES in utero have one or more of these structural abnormalities, in comparison with 5% to 8% of unexposed men. Other studies have shown no differences (Leary et al., 1984; Vessey et al., 1983).
Suspected Effects and Emerging Research
An association between DES exposure and testicular cancer is not certain. Previous studies have shown no association between DES exposure in utero and testicular cancer (Brown et al., 1986; Gershman et al., 1988; Leary et al., 1984). Others, however, have found an increased risk (Depue et al., 1983; Henderson et al., 1979; Moss et al., 1986; Schottenfeld et al., 1980).
The only definitive prospective study to date of the association between in utero exposure to DES and testicular cancer indicated that levels of testicular cancer were elevated, though not to a statistically significant extent, among DES-exposed men (Strohsnitter et al., 2001). The study found it unlikely that DES exposure is heavily associated with testicular cancer, but concluded that the findings did “lend support to the hypothesis that the prenatal hormonal environment may influence the development of testicular cancer in adults” and suggest follow-up study of DES men for increased risk of testicular cancer (Strohsnitter et al., 2001, p. 550).
Up until recently, there had been little research on the impact of DES on male fertility. One controlled clinical trial indicated that some DES-exposed sons had a higher rate of abnormal sperm and low sperm counts (Gill et al., 1979). The average total dosage of DES received by these sons’ mothers was more than 12,000 mg. A second observational study found no increase in sperm abnormalities in men exposed to lower doses of DES (Leary et al., 1984). In this second study, the total average DES dosage was 1,429 mg.
In 1995, Wilcox and colleagues conducted a 40-year follow-up of subjects from a prospective, blind, placebo-controlled study (Dieckmann et al., 1953) and found no de facto impairment of fertility. Despite earlier findings to the contrary, this study showed that DES sons were able to father children at approximately the same rate as non-exposed men.
Mouse studies have demonstrated an association between DES exposure and an increased rate of rete testis cancer and prostate cancer (McLaughlan et al., 1998; Newbold et al., 1985, 1987). No human studies have found similar risks in DES sons. However, these cancers have been found in older mice; if DES sons are at increased risk, they may not yet have reached a comparable age.
Studies of cancer, heart disease, and autoimmune diseases among DES sons are ongoing.
Screening and Treatment
Conditions decreasing male fertility frequently progress and worsen over time. DES sons may wish to have a semen analysis to help them plan the timing of their family.
Researchers are currently examining the effects of DES exposure on the grandchildren of women prescribed DES while pregnant. Some animal studies have shown increased tumor rates in third-generation mice as they age. A small clinical study did not find evidence of structural reproductive abnormalities in 28 DES granddaughters (Kaufman et al., 2000). A larger survey is under way to determine if there are increased risks of reproductive problems and cancer. The findings of Klip and associates (2002), who studied the sons of a Dutch cohort of women who had been exposed to DES in utero, suggested that these sons may have an increased risk of hypospadias; however, further study is necessary.
There are several DES resources for clinicians and patients.
DES Action USA
610 16th Street, Suite 301
Oakland, CA 94612
Voice: (510) 465-4011
Fax: (510) 465-4815
A national consumer organization representing DES mothers, daughters, and sons. Dedicated to informing the public and health professionals about the effects of DES and what can be done about them, and to promoting DES research. Offers physician referrals, special publications, and a quarterly newsletter (DES Action Voice).
DES Cancer Network
514 10th Street, NW
Washington, D.C. 20004-1403
Voice: (800) DESNET-4, (202) 628-6330
Fax: (202) 628-6217
Web site: www.descancer.org
A national network for DES-exposed women and men with a special focus on DES research advocacy, programs for DES-exposed people coping with cancer, and communication about DES issues. Offers information, peer support, medical referrals, and a newsletter (DES Issues).
DES Sons Network
DES Action/DES Sons Network
104 Sleepy Hollow Place
Cherry Hill, NJ 08003
Voice: (856) 795-1658
Fax: (856) 795-1658
A national network providing information and support for men exposed to DES before birth (DES Sons), and counseling for men with testicular cancer.
DES Third Generation Network
Mahwah, NJ 07430
An advocacy network designed to collect and share information about the health of children born to DES Daughters (women exposed to DES before birth [in the womb]) and DES Sons (men exposed to DES before birth [in the womb]).
National Cancer Institute
Cancer Information Service
M-F 9:00 a.m. to 7:00 p.m.
(800) 4-CANCER or (800) 422-6237
A national service providing free, accurate, up-to-date information on cancer to patients and their families, to health professionals, and to the general public.
Registry for Research on Hormonal Transplacental Carcinogenesis
Department of Obstetrics and Gynecology
The University of Chicago
5841 South Maryland Avenue
Mail Code 2050
Chicago, IL 60637
Voice: (773) 702-6671
Fax: (773) 702-0840
An international research registry of cancer patients with clear cell adenocarcinoma (CCA) of the vagina and/or cervix or other gynecologic cancer who may or may not have been exposed to DES or other synthetic hormones while in utero. A resource for clinicians and scientists, the Registry was established in 1971 to centralize data collection on CCA and enable us to learn more about the epidemiology and pathology of these tumors.
Nonsteroidal Estrogen-Androgren Combination
Vaginal Cream Suppositories with Nonsteroidal Estrogens
Source: National Cancer Institute. Exposure in utero to diethylstilbestrol and related synthetic hormones. JAMA 1976 Sept 6; 236 (10): 1107-1109.
Bibbo, M., et al. (1977). Follow up study of male and female offspring of DES exposed mothers. Obstetrics and Gynecology, 49, 1–8.
Brown, L. M., et al.(1986). Prenatal and perinatal risk factors for testicular cancer. Cancer Research, 46, 4812–4816.
Conley, G. R., et al. (1983). Seminoma and epididymal cysts in a young man with known diethylstilbestrol exposure in utero. Journal of the American Medical Association, 249, 1325–1326.
Depue, R. H., et al. (1983). Estrogen exposure during gestation and risk of testicular cancer. Journal of the National Cancer Institute, 71, 1151–1155.
Gershman, S. T., et al. (1988). A case control study of testicular cancer using Connecticut Tumor Registry data. International Journal of Epidemiology, 17, 738–742.
Gill, W. B. (1988). Effects on human males of in utero exposure to exogenous sex hormones. In T. Mori & H. Nagasawa (Eds.), Toxicity of hormones in perinatal life. Boca Raton, FL: CRS Press.
Gill, W. B., et al. (1979). Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia, and semen abnormalities. Journal of Urology, 122, 36–39.
Henderson, B. E., et al. (1979). Risk factors for cancer of the testis in young men. International Journal of Cancer, 23, 598–602.
Kaufman, R. H., et al. (2000). Pregnancy outcomes in diethylstilbestrol-exposed offspring: Continued follow-up. Obstetrics and Gynecology, 96, 483–489.
Klip, H., et al. (2002). Hypospadias in sons of women exposed to diethylstilbestrol in utero: A cohort study. Lancet, 359, 1081–1082.
Leary, F. J., et al. (1984). Males exposed in utero to diethylstilbestrol. Journal of the American Medical Association, 252, 2984–2989.
McLaughlan, J. A., et al.(1998). Are estrogens carcinogenic during development of the testes? APMIS, 106, 240–244.
Moss, A. R., et al. (1986). Hormonal risk factors in testicular cancer: A case-control study. American Journal of Epidemiology, 124, 39–52.
Newbold, R. R., et al. (1985). Lesions of the rete testis in mice exposed prenatally to diethylstilbestrol. Cancer Research, 45, 5145–5150.
Newbold, R. R., et al. (1987). Testicular tumors in mice exposed in utero to diethylstilbestrol. Journal of Urology, 138, 1446–1450.
Niculescu, A. (1985). Effects of in utero exposure to DES on male progeny. Journal of Obstetric, Gynecologic, and Neonatal Nursing, 14, 468–470.
Schottenfeld, D., et al. (1980). The epidemiology of testicular cancer in young adults. American Journal of Epidemiology, 112, 232–246.
Strohsnitter, W. C., et al. (2001). Cancer risk in men exposed in utero to diethylstilbestrol. Journal of the National Cancer Institute, 93, 545–551.
Vessey, M. P., et al. (1983). A randomized double blind controlled trial of the value of stilbestrol therapy in pregnancy: Long term follow up of mothers and their offspring. British Journal of Obstetrics and Gynaecology, 90, 1007–1017.
Wilcox, A. J., et al. (1995). Fertility in men exposed pre-natally to diethylstilbestrol. New England Journal of Medicine, 332, 1411–1416.