Follow-up of DES Exposed Cohorts
The Slone Epidemiology Center is participating in a collaborative follow-up study of the long-term health effects of diethylstilbestrol (DES) exposure, with 4 other academic research centers and the National Cancer Institute. All previously studied cohorts of DES-exposed and unexposed persons were identified and combined in 1992 to create a cohort of mothers, a cohort of daughters, and a cohort of sons. The mothers’ cohort received one questionnaire (1994) and has been followed passively for deaths since that time. The sons’ and daughters’ cohort have been followed by periodic mailed questionnaire (1994, 1997, 2001, 2006, 2011, and 2016) for assessment of changes in health status and changes in exposures. Disease rates in the exposed cohorts will be compared with disease rates in the unexposed cohorts. The principal aim is to evaluate whether DES exposure increases the incidence of cancer in the offspring of women who took DES while pregnant. In particular, we will evaluate the relation of prenatal DES exposure to risk of breast cancer in the daughters and risk of prostate cancer in the sons. Because many DES daughters have expressed concerns about whether their own daughters will experience health problems due to the DES exposure, we have begun the Third Generation Study. As with our earlier studied cohorts, we compare two groups of women: those whose mothers were exposed to DES in utero and those whose mothers were not. Investigators at the Slone Center have led analyses and manuscript preparation on DES in relation to infertility in the daughters, breast cancer in the daughters, and hypospadias in the grandsons.
For more information, please visit the DES Follow-up Study website.
Investigators and Study Staff
Investigators:
Julie R. Palmer, Sc.D., Principal Investigator
Professor of Epidemiology
Slone Epidemiology Center at Boston University
Elizabeth E. Hatch, Ph.D., Co-Investigator
Professor of Epidemiology
Boston University School of Public Health
Kimberly A. Bertrand, Sc.D., Co-Investigator
Assistant Professor of Medicine
Slone Epidemiology Center at Boston University
Study Staff:
Hannah Lord, Research Coordinator
Study Details
Collaborating Centers:
- Baylor College of Medicine (Ervin Adam, M.D.)
- Tufts Medical Center (William C. Strohsnitter, D.Sc.)
- Dartmouth-Hitchcock Medical Center (Linda Titus-Ernstoff, Ph.D.)
- University of Chicago (Arthur L. Herbst, M.D.)
- National Cancer Institute (Robert N. Hoover, M.D.)
Source of Funding:
National Cancer Institute
Study Period:
1992 to present
Presentations
- Palmer JR. American Association for Cancer Research Annual Meeting, Anaheim, CA, April 2005. Prenatal DES exposure and risk of breast cancer.
- Palmer JR. Harvard School of Public Health Seminar, Boston, MA, January 15, 2003. The relation of prenatal DES exposure to risk of breast cancer.
- Palmer JR. Society of Epidemiologic Research, Seattle, WA, June 16, 2000. Infertility among women exposed prenatally to diethylstilbestrol.
Publications
- Troisi R, Hyer M, Titus L, Palmer JR, Hatch EE, Huo D, Aagaard KM, Strohsnitter WC, Hoover RN. Prenatal diethylstilbestrol exposure and risk of diabetes, gallbladder disease, and pancreatic disorders and malignancies. J Dev Orig Health Dis 2020. doi: 10.1017/S2040174420000872 (epub ahead of print).
- Troisi R, Palmer JR, Hatch EE, Strohsnitter WC, Huo D, Hyer M, Fredriksen-Goldsen KI, Hoover R, Titus L. Gender identity and sexual orientation identity in women and men prenatally exposed to diethylstilbestrol. Arch Sex Behav 2020;49(2):447-54. doi: 10.1007/s10508-020-01637-7.
- Titus L, Hatch EE, Palmer JR, Huo D, Strohsnitter WC, Adam E, Ricker W, Hyer M, Hoover RN, Troisi R. Prenatal diethylstilbestrol exposure and risk of depression in women and men. Epidemiology 2019. doi: 10.1097/EDE.0000000000001048 (epub ahead of print).
- Titus L, Hatch EE, Drake KM, Parker SE, Hyer M, Palmer JR, Strohsnitter WC, Adam E, Herbst AL, Huo D, Hoover RN, Troisi R. Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): a report from the US National Cancer Institute DES Third Generation Study. Reprod Toxicol 2019;84:32-8. doi: 10.1016/j.reprotox.2018.12.008. PMCID: PMC6382553.
- Troisi R, Hatch E, Palmer JR, Titus L, Sampson J, Xu X, Hoover RN. Estrogen metabolism in postmenopausal women exposed in-utero to diethylstilbestrol. Cancer Epidemiol Biomarkers Prev 2018;27(10):1208-13. doi: 10.1158/1055-9965.EPI-18-0135. PMCID: PMC6170707.
- Strohsnitter WC, Bertrand KA, Troisi R, Scott CG, Cheville AL, Hoover RN, Palmer JR, Vachon CM. Prenatal diethylstilbestrol exposure and mammographic density. Int J Cancer 2018;143(6):1374-8. doi: 10.1002/ijc.31524. PMCID: PMC Journal – In Process.
- Troisi R, Hatch EE, Titus L, Strohsnitter W, Gail MH, Huo D, Adam E, Robboy SJ, Hyer M, Hoover RN, Palmer JR. Prenatal diethylstilbestrol exposure and cancer risk in women. Environ Mol Mutagen 2019;60(5):395-403. doi: 10.1002/em.22155.
- Troisi R, Titus L, Hatch EE, Palmer JR, Huo D, Strohsnitter WC, Adam E, Ricker W, Hyer M, Hoover RN. A prospective cohort study of prenatal diethylstilbestrol exposure and cardiovascular disease risk. J Clin Endocrinol Metab 2018;103(1):206-12. doi: 10.1210/jc.2017-01940. PMCID: PMC5761490.
- Huo D, Anderson D, Palmer JR, Herbst AL. Incidence rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: update after 40-year follow-up. Gynecol Oncol 2017;146(3):566-71. doi: 10.1016/j.ygyno.2017.06.028. PMCID: PMC Journal – In Process.
- Troisi R, Hatch EE, Palmer JR, Titus L, Robboy SJ, Strohsnitter WC, Herbst AL, Adam E, Hyer M, Hoover RN. Prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract. Am J Obstet Gynecol 2016;215(3):322.e1-8. doi: 10.1016/j.ajog.2016.03.007. PMCID: PMC5003722.
- Hatch EE, Troisi R, Palmer JR, Wise LA, Titus L, Strohsnitter WC, Ricker W, Hyer M, Hoover RN. Prenatal diethylstilbestrol exposure and risk of obesity in adult women. J Dev Orig Health Dis 2015;6(3):201-7. doi: 10.1017/S2040174415000033.
- Parker SE, Troisi R, Wise LA, Palmer JR, Titus-Ernstoff L, Strohsnitter WC, Hatch EE. Menarche, menopause, years of menstruation, and the incidence of osteoporosis: the influence of prenatal exposure to diethylstilbestrol. J Clin Endocrinol Metab 2014;99(2):594-601. doi: 10.1210/jc.2013-2954.
- Palmer JR, Boggs DA, Hatch EE, Troisi R, Titus-Ernstoff L, Strohsnitter WC, Adam E, Hoover RN. Prenatal DES exposure in relation to breast size. Cancer Causes Control 2013;24(9):1757-61. doi: 10.1007/s10552-013-0248-3.
- Troisi R, Hyer M, Hatch EE, Titus-Ernstoff L, Palmer JR, Strohsnitter WC, Herbst AL, Adam E, Hoover RN. Medical conditions among adult offspring prenatally exposed to diethylstilbestrol. Epidemiology 2013;24(3):430-8. doi: 10.1097/EDE.0b013e318289bdf7.
- Hoover RN, Hyer M, Pfeiffer RM, Adam E, Bond B, Cheville AL, Colton T, Hartge P, Hatch EE, Herbst AL, Karlan BY, Kaufman R, Noller KL, Palmer JR, Robboy SJ, Saal RC, Strohsnitter W, Titus-Ernstoff L, Troisi R. Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med 2011;365:1304-14.
- Hatch EE, Troisi R, Wise LA, Titus-Ernstoff L, Hyer M, Palmer JR, Strohsnitter WC, Robboy SJ, Anderson D, Kaufman R, Adam E, Hoover RN. Preterm birth, fetal growth, and age at menarche among women exposed prenatally to diethylstilbestrol (DES). Reprod Toxicol 2011;31(2):151-7. doi: 10.1016/j.reprotox.2010.11.006. PMCID: PMC3057340.
- Titus-Ernstoff L, Troisi R, Hatch EE, Palmer JR, Hyer M, Kaufman R, Adam E, Noller K, Hoover RN. Birth defects in the sons and daughters of women who were exposed in utero to diethylstilbestrol (DES). Int J Androl 2010;33(2):377-84. doi: 10.1111/j.1365-2605.2009.01010.x. PMCID: PMC2874639.
- Strohsnitter WC, Noller KL, Troisi R, Robboy SJ, Hatch EE, Titus-Ernstoff L, Kaufman RH, Palmer JR, Anderson D, Hoover RN. Autoimmune disease incidence among women prenatally exposed to diethylstilbestrol. J Rheumatol 2010;37(10):2167-73. doi: 10.3899/jrheum.091092.
- Palmer JR, Herbst AL, Noller KL, Boggs DA, Troisi R, Titus-Ernstoff L, Hatch EE, Wise LA, Strohsnitter WC, Hoover RN. Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study. Environ Health 2009;8:37. doi: 10.1186/1476-069X-8-37. PMCID: PMC2739506.
- Titus-Ernstoff L, Troisi R, Hatch EE, Hyer M, Wise LA, Palmer JR, Kaufman R, Adam E, Noller K, Herbst AL, Strohsnitter W, Cole BF, Hartge P, Hoover RN. Offspring of women exposed in utero to diethylstilbestrol (DES): a preliminary report of benign and malignant pathology in the third generation. Epidemiology 2008;19:251-7. doi: 10.1097/EDE.0b013e318163152a.
- Strohsnitter WC, Hatch EE, Hyer M, Troisi R, Kaufman R, Robboy SJ, Palmer JR, Titus-Ernstoff L, Anderson D, Hoover RN, Noller KL. The association between in utero cigarette smoke exposure and age at menopause. Am J Epidemiol 2008;167(6):727-33.
- Troisi R, Titus-Ernstoff L, Hyer M, Hatch EE, Robboy SJ, Strohsnitter W, Palmer JR, Øgloend B, Adam E, Kaufman R, Herbst AL, Hoover RN. Preeclampsia risk in women exposed in utero to diethylstilbestrol. Obstet Gynecol 2007;110(1):113-20.
- Troisi R, Hatch EE, Titus-Ernstoff L, Hyer M, Palmer JR, Robboy SJ, Strohsnitter WC, Kaufman R, Herbst AL, Hoover RN. Cancer risk in women prenatally exposed to diethylstilbestrol. Int J Cancer 2007;121(2):356-60. doi: 10.1002/ijc.22631.
- Wise LA, Palmer JR, Hatch EE, Troisi R, Titus-Ernstoff L, Herbst AL, Kaufman R, Noller KL, Hoover RN. Secondary sex ratio among women exposed to diethylstilbestrol in utero. Environ Health Perspect 2007;115(9):1314-9. PMCID: PMC1964903.
- Wise LA, Titus-Ernstoff L, Palmer JR, Hoover RN, Hatch EE, Perez KM, Strohsnitter WC, Kaufman R, Anderson D, Troisi R. Time to pregnancy and secondary sex ratio in men exposed prenatally to diethylstilbestrol. Am J Epidemiol 2007;166:765-74.
- Titus-Ernstoff L, Troisi R, Hatch EE, Palmer JR, Wise LA, Ricker W, Hyer M, Kaufman R, Noller K, Strohsnitter W, Herbst AL, Hartge P, Hoover RN. Mortality in women given diethylstilbestrol during pregnancy. Br J Cancer 2006;95(1):107-11. doi: 10.1038/sj.bjc.6603221.
- Larson PS, Ungarelli RA, de las Morenas A, Cupples LA, Rowlings K, Palmer JR, Rosenberg CL. In utero exposure to diethylstilbestrol (DES) does not increase genomic instability in normal or neoplastic breast epithelium. Cancer 2006;107:2122-6.
- Palmer JR, Wise LA, Hatch EE, Troisi R, Titus-Ernstoff L, Strohsnitter W, Kaufman R, Herbst AL, Noller KL, Hyer M, Hoover RN. Prenatal diethylstilbestrol exposure and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2006;15(8):1509-14.
- Hatch EE, Troisi R, Wise LA, Hyer M, Palmer JR, Titus-Ernstoff L, Strohsnitter WC, Kaufman R, Adam E, Noller K, Herbst A, Robboy S, Hartge P, Hoover RN. Age at natural menopause in women exposed to diethylstilbestrol in utero. Am J Epidemiol 2006;164(7):682-8.
- Titus-Ernstoff L, Troisi R, Hatch EE, Wise LA, Palmer JR, Hyer M, Kaufman R, Adam E, Strohsnitter W, Noller K, Herbst AL, Gibson-Chambers J, Hartge P, Hoover RN. Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES). Int J Epidemiol 2006;35:862-8.
- Troisi R, Hatch EE, Titus-Ernstoff L, Palmer JR, Hyer M, Strohsnitter WC, Robboy SJ, Kaufman R, Herbst A, Adam E, Hoover RN. Birth weight and breast cancer risk. Br J Cancer 2006;94(11):1734-7.
- Perez KM, Titus-Ernstoff L, Hatch EE, Troisi R, Wactawski-Wende J, Palmer JR, Noller K, Hoover RN, and the National Cancer Institute’s DES Follow-up Study Group. Reproductive outcomes in men with prenatal exposure to diethylstilbestrol. Fertil Steril 2005;84(6):1649-56.
- Palmer JR, Wise LA, Robboy SJ, Titus-Ernstoff L, Noller KL, Herbst AL, Troisi R, Hoover RN. Hypospadias in sons of women exposed to diethylstilbestrol in utero. Epidemiology 2005;16(4):583-6.
- Wise LA, Palmer JR, Rowlings K, Kaufman RH, Herbst AL, Noller KL, Titus-Ernstoff L, Troisi R, Hatch EE, Robboy SJ. Risk of benign gynecologic tumors in relation to prenatal diethylstilbestrol exposure. Obstet Gynecol 2005;105(1):167-73.
- Titus-Ernstoff L, Perez K, Hatch EE, Troisi R, Palmer JR, Hartge P, Hyer M, Kaufman R, Adam E, Strohsnitter W, Noller K, Pickett K, Hoover R. Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol. Epidemiology 2003;14:155-60.
- Palmer JR, Hatch EE, Rosenberg CL, Hartge P, Kaufman RH, Titus-Ernstoff L, Noller KL, Herbst AL, Rao RS, Troisi R, Colton T, Hoover RN. Risk of breast cancer in women exposed to diethylstilbestrol in utero: preliminary results (United States). Cancer Causes Control 2002;13:751-8.
- Hatch EE, Herbst AL, Hoover RN, Noller KL, Adam E, Kaufman RH, Palmer JR, Titus-Ernstoff L, Hyer M, Hartge P, Robboy SJ. Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States). Cancer Causes Control 2001;12:837-45.
- Palmer JR, Hatch EE, Rao RS, Kaufman RH, Herbst AL, Noller KL, Titus-Ernstoff L, Hoover RN. Infertility among women exposed prenatally to diethylstilbestrol. Am J Epidemiol 2001;154:316-21.
- Strohsnitter WC, Noller KL, Hoover RN, Robboy SJ, Palmer JR, Titus-Ernstoff L, Kaufman RH, Adam E, Herbst AL, Hatch EE. Cancer risk in men exposed in utero to diethylstilbestrol. J Natl Cancer Inst 2001;93:545-51.
- Titus-Ernstoff L, Hatch EE, Hoover RN, Palmer JR, Greenberg ER, Ricker W, Kaufman R, Noller K, Herbst AL, Colton T, Hartge P. Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy. Br J Cancer 2001;84:126-33.
- Hatch EE, Herbst AL, Hoover RN, Noller KL, Adam E, Kaufman RH, Palmer JR, Titus-Ernstoff L, Hyer M, Hartge P, Robboy SJ. Incidence of squamous neoplasia of the cervix and vagina in DES-exposed daughters [abstract]. Ann Epidemiol 2000;10(7):467.
- Kaufman RH, Adam E, Hatch EE, Noller K, Herbst AL, Palmer JR, Hoover RN. Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring. Obstet Gynecol 2000;96:483-9.
- Palmer JR, Anderson D, Helmrich SP, Herbst AL. Risk factors for diethylstilbestrol-associated clear cell adenocarcinoma. Obstet Gynecol 2000;95:814-20.
- Hatch EE, Palmer JR, Titus-Ernstoff L, Noller KL, Kaufman RH, Mittendorf R, Robboy SJ, Hyer M, Cowan CM, Adam E, Colton T, Hartge P, Hoover RN. Cancer risk in women exposed to diethylstilbestrol in utero. J Am Med Assoc 1998;280:630-4.