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Prenatal diethylstilbestrol exposure and risk of obesity in adult women

Published online by Cambridge University Press:  20 February 2015

E. E. Hatch Open the ORCID record for E. E. Hatch [Opens in a new window] ,
R. Troisi ,
J. R. Palmer Open the ORCID record for J. R. Palmer [Opens in a new window] ,
L. A. Wise ,
L. Titus ,
W. C. Strohsnitter ,
W. Ricker ,
M. Hyer  and
R. N. Hoover
E. E. Hatch*
Affiliation:
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
R. Troisi
Affiliation:
Division of Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
J. R. Palmer
Affiliation:
Slone Epidemiology Center, Boston University, Boston, MA, USA
L. A. Wise
Affiliation:
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA Slone Epidemiology Center, Boston University, Boston, MA, USA
L. Titus
Affiliation:
Geisel School of Medicine at Dartmouth, Hood Center for Children and Families, Lebanon, NH, USA
W. C. Strohsnitter
Affiliation:
Department of Obstetrics and Gynecology, Tufts New England Medical Center, Boston, MA, USA
W. Ricker
Affiliation:
Information Management Services, Rockville, MD, USA
M. Hyer
Affiliation:
Information Management Services, Rockville, MD, USA
R. N. Hoover
Affiliation:
Division of Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
*
*Address for correspondence: E. E. Hatch, Department of Epidemiology, Boston University School of Public Health, 715 Albany Street Talbot 318E, Boston, MA 02118, USA. (Email [email protected])
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Abstract

Diethylstilbestrol (DES) is a non-steroidal estrogen that was commonly prescribed during pregnancy from the late 1940s to 1971. A potent endocrine disruptor, prenatal DES exposure has been linked with reproductive tract malformations, adverse pregnancy outcomes, cancer, infertility and earlier menopause. DES was used for years as a growth promoter in animal production. Some animal studies suggest that prenatal DES exposure is associated with obesity and metabolic disturbances. Using data from the National Cancer Institute DES Follow-Up Study, we evaluated the association between DES and adult obesity, weight gain from age 20 to mid-life, central adiposity and height among 2871 prenatally exposed and 1352 unexposed women between 23 and 52 years of age (median 41.5) at baseline in 1994. DES exposure status was confirmed by prenatal medical record review. We used multivariable log-binomial models to calculate risk ratios (RRs) for obesity in 2006, and linear regression to calculate mean differences in body mass index, weight gain, waist circumference and height. The adjusted RR for DES and obesity was 1.09 [95% confidence interval (CI): 0.97, 1.22], and RRs were 1.23 (CI: 1.07, 1.42) and 1.05 (CI: 0.91, 1.20) for low and high estimated total DES dose, respectively, compared with no exposure. DES-exposed women gained slightly more weight than unexposed women [mean difference, 0.70 kg (CI: −0.27, 1.66)]. This study suggests that prenatal DES exposure may be associated with a small increase in adult obesity.

Keywords

adultepidemiology/public healthhumanpregnancy
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 6 , Issue 3 , June 2015 , pp. 201 - 207
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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References

1. Herbst, AL, Ulfelder, H, Poskanzer, DC. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971; 284, 878–881, [Epub 15 April 1971].Google Scholar
2. Hoover, RN, Hyer, M, Pfeiffer, RM, et al. Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med. 2011; 365, 1304–1314, [Epub 14 October 2011].Google Scholar
3. Noller, KL, Fish, CR. Diethylstilbestrol usage: its interesting past, important present, and questionable future. Med Clin North Am. 1974; 58, 793–810, [Epub 1 July 1974].Google Scholar
4. McMartin, KE, Kennedy, KA, Greenspan, P, et al. Diethylstilbestrol: a review of its toxicity and use as a growth promotant in food-producing animals. J Environ Pathol Toxicol. 1978; 1, 279–313, [Epub 1 January 1978].Google Scholar
5. Newbold, RR, Padilla-Banks, E, Jefferson, WN, Heindel, JJ. Effects of endocrine disruptors on obesity. Int J Androl. 2008; 31, 201–208, [Epub 5 March 2008].Google Scholar
6. Newbold, RR, Padilla-Banks, E, Snyder, RJ, Jefferson, WN. Perinatal exposure to environmental estrogens and the development of obesity. Mol Nutr Food Res. 2007; 51, 912–917, [Epub 3 July 2007].Google Scholar
7. Ryan, KK, Haller, AM, Sorrell, JE, et al. Perinatal exposure to bisphenol-a and the development of metabolic syndrome in CD-1 mice. Endocrinology. 2010; 151, 2603–2612, [Epub 31 March 2010].Google Scholar
8. Grun, F, Blumberg, B. Endocrine disrupters as obesogens. Mol Cell Endocrinol. 2009; 304, 19–29, [Epub 13 May 2009].Google Scholar
9. Heindel, JJ. Endocrine disruptors and the obesity epidemic. Toxicol Sci. 2003; 76, 247–249, [Epub 18 December 2003].Google Scholar
10. Newbold, RR, Padilla-Banks, E, Jefferson, WN. Environmental estrogens and obesity. Mol Cell Endocrinol. 2009; 304, 84–89, [Epub 13 May 2009].Google Scholar
11. Hao, CJ, Cheng, XJ, Xia, HF, Ma, X. The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice. Toxicol Appl Pharmacol. 2012; 263, 102–110, [Epub 20 June 2012].Google Scholar
12. Hatch, EE, Nelson, JW, Stahlhut, RW, Webster, TF. Association of endocrine disruptors and obesity: perspectives from epidemiological studies. Int J Androl. 2010; 33, 324–332, [Epub 2 February 2010].Google Scholar
13. Tang-Peronard, JL, Andersen, HR, Jensen, TK, Heitmann, BL. Endocrine-disrupting chemicals and obesity development in humans: a review. Obes Rev. 2011; 12, 622–636, [Epub 5 April 2011].Google Scholar
14. Jensen, ET, Longnecker, MP. Pharmacologic sex hormones in pregnancy in relation to offspring obesity. Obesity (Silver Spring). 2014; 22, 2406–2412, [Epub 25 April 2014].Google Scholar
15. Hatch, EE, Palmer, JR, Titus-Ernstoff, L, et al. Cancer risk in women exposed to diethylstilbestrol in utero. J Am Med Assoc. 1998; 280, 630–634, [Epub 26 August 1998].Google Scholar
16. Labarthe, D, Adam, E, Noller, KL, et al. Design and preliminary observations of National Cooperative Diethylstilbestrol Adenosis (DESAD) Project. Obstet Gynecol. 1978; 51, 453–458, [Epub 1 April 1978].Google Scholar
17. Dieckmann, WJ, Davis, ME, Rynkiewicz, LM, Pottinger, RE. Does the administration of diethylstilbestrol during pregnancy have therapeutic value? Am J Obstet Gynecol. 1953; 66, 1062–1081.CrossRefGoogle ScholarPubMed
18. Greenberg, ER, Barnes, AB, Resseguie, L, et al. Breast cancer in mothers given diethylstilbestrol in pregnancy. N Engl J Med. 1984; 311, 1393–1398, [Epub 29 November 1984].Google Scholar
19. Smith, OW, Smith, GVS, Hurwitz, D. Increased excretion of pregnanediol in pregnancy from diethylstilbestrol with special reference to the prevention of late pregnancy accidents. Med Rec Ann. 1946; 40, 1669–1671, [Epub 1 December 1946].Google Scholar
20. Palmer, JR, Wise, LA, Hatch, EE, et al. Prenatal diethylstilbestrol exposure and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2006; 15, 1509–1514, [Epub 10 August 2006].Google Scholar
21. SAS Institute. I. SAS/STAT ® 9.2 User’s Guide . 2008. SAS Institute: Cary, NC.Google Scholar
22. Hatch, EE, Troisi, R, Wise, LA, et al. Preterm birth, fetal growth, and age at menarche among women exposed prenatally to diethylstilbestrol (DES). Reprod Toxicol. 2011; 31, 151–157, [Epub 7 December 2010].Google Scholar
23. D’Aloisio, AA, DeRoo, LA, Baird, DD, Weinberg, CR, Sandler, DP. Prenatal and infant exposures and age at menarche. Epidemiology. 2013; 24, 277–284, [Epub 26 January 2013].Google Scholar
24. Troisi, R, Hyer, M, Hatch, EE, et al. Medical conditions among adult offspring prenatally exposed to diethylstilbestrol. Epidemiology. 2013; 24, 430–438, [Epub 12 March 2013].Google Scholar
25. Reagan-Shaw, S, Nihal, M, Ahmad, N. Dose translation from animal to human studies revisited. FASEB J. 2008; 22, 659–661, [Epub 19 October 2007].Google Scholar
26. Poissonnet, CM, Burdi, AR, Garn, SM. The chronology of adipose tissue appearance and distribution in the human fetus. Early Hum Dev. 1984; 10, 1–11, [Epub 1 September 1984].Google Scholar
27. Poissonnet, CM, Burdi, AR, Bookstein, FL. Growth and development of human adipose tissue during early gestation. Early Hum Dev. 1983; 8, 1–11, [Epub 1 March 1983].Google Scholar
28. Sarr, O, Yang, K, Regnault, TR. In utero programming of later adiposity: the role of fetal growth restriction. J Pregnancy. 2012; 2012, 134758, [Epub 20 December 2012].Google Scholar
29. Andersen, CS, Fei, C, Gamborg, M, et al. Prenatal exposures to perfluorinated chemicals and anthropometric measures in infancy. Am J Epidemiol. 2010; 172, 1230–1237, [Epub 14 October 2010].Google Scholar
30. Halldorsson, TI, Rytter, D, Haug, LS, et al. Prenatal exposure to perfluorooctanoate and risk of overweight at 20 years of age: a prospective cohort study. Environ Health Perspect. 2012; 120, 668–673, [Epub 7 February 2012].Google Scholar
31. Mendez, MA, Garcia-Esteban, R, Guxens, M, et al. Prenatal organochlorine compound exposure, rapid weight gain, and overweight in infancy. Environ Health Perspect. 2011; 119, 272–278, [Epub 7 October 2010].Google Scholar
32. Smink, A, Ribas-Fito, N, Garcia, R, et al. Exposure to hexachlorobenzene during pregnancy increases the risk of overweight in children aged 6 years. Acta Paediatr. 2008; 97, 1465–1469, [Epub 31 July 2008].Google Scholar
33. Hurst, CH, Waxman, DJ. Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol Sci. 2003; 74, 297–308.Google Scholar
34. Grun, F, Blumberg, B. Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Rev Endocr Metab Disord. 2007; 8, 161–171, [Epub 28 July 2007].Google Scholar
35. Oken, E, Levitan, EB, Gillman, MW. Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis. Int J Obes (Lond). 2008; 32, 201–210, [Epub 19 February 2008].Google Scholar
36. Newbold, RR, Padilla-Banks, E, Jefferson, WN. Adverse effects of the model environmental estrogen diethylstilbestrol are transmitted to subsequent generations. Endocrinology. 2006; 147(Suppl. 6), S11–S17, [Epub 13 May 2006].Google Scholar
37. McLachlan, JA, Burow, M, Chiang, TC, Li, SF. Gene imprinting in developmental toxicology: a possible interface between physiology and pathology. Toxicol Lett. 2001; 120, 161–164, [Epub 27 April 2001].Google Scholar
38. Nelson, KG, Sakai, Y, Eitzman, B, Steed, T, McLachlan, J. Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen-regulated genes. Cell Growth Differ. 1994; 5, 595–606, [Epub 1 June 1994].Google Scholar
39. Peress, MR, Tsai, CC, Mathur, RS, Williamson, HO. Hirsutism and menstrual patterns in women exposed to diethylstilbestrol in utero. Am J Obstet Gynecol. 1982; 144, 135–140, [Epub 15 September 1982].Google Scholar
40. Wise, LA, Troisi, R, Hatch, EE, Titus, LJ, Rothman, KJ, Harlow, BL. Prenatal exposure to diethylstilbestrol and reproductive hormones in premenopausal women. Am J Epidemiol . 2013; S53, accepted January 2015, JDOHAD.Google Scholar
41. Wu, CH, Mangan, CE, Burtnett, MM, Mikhail, G. Plasma hormones in DES-exposed females. Obstet Gynecol. 1980; 55, 157–162, [Epub 1 February 1980].Google Scholar
42. Rothman, KJ. BMI-related errors in the measurement of obesity. Int J Obes (Lond). 2008; 32(Suppl. 3), S56–S59, [Epub 21 August 2008].Google Scholar
43. Colton, T, Greenberg, ER, Noller, K, et al. Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up. JAMAJ Am Med Assoc. 1993; 269, 2096–2100, [Epub 28 April 1993].Google Scholar
44. Tie, HT, Xia, YY, Zeng, YS, et al. Risk of childhood overweight or obesity associated with excessive weight gain during pregnancy: a meta-analysis. Arch Gynecol Obstet. 2014; 289, 247–257, [Epub 22 October 2013].Google Scholar