Biomaterial Database

Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES). 2006

Linda Titus-Ernstoff, and Rebecca Troisi, and Elizabeth E Hatch, and Lauren A Wise, and Julie Palmer, and Marianne Hyer, and Raymond Kaufman, and Ervin Adam, and William Strohsnitter, and Kenneth Noller, and Arthur L Herbst, and Jennifer Gibson-Chambers, and Patricia Hartge, and Robert N Hoover

Department of Community and Family Medicine, Dartmouth Medical School, and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA. Linda.Titus-Ernstoff@Dartmouth.edu

BACKGROUND In women, prenatal exposure to diethylstilbestrol (DES) is associated with adult reproductive dysfunction. The mouse model, which replicates many DES outcomes, suggests DES causes epigenetic alterations, which are transmissable to daughters of prenatally exposed animals. We report menstrual and reproductive characteristics in a unique cohort comprising daughters of women exposed prenatally to DES. METHODS Menstrual and reproductive outcomes and baseline characteristics were assessed by mailed questionnaire in 793 women whose mothers had documented information regarding in utero DES exposure. RESULTS Mean age at menarche was 12.6 years in both groups, but daughters of the exposed women attained menstrual regularization later (mean age of 16.2 years vs. 15.8 years; P = 0.05), and were more likely to report irregular menstrual periods, odds ratio (OR) = 1.54 [95% confidence interval (95% CI 1.02-2.32)]. A possible association between mothers' DES exposure and daughters' infertility was compatible with chance, age, and cohort adjusted OR = 2.19 (95% CI 0.95-5.07). We found limited evidence that daughters of the exposed had more adverse reproductive outcomes, but daughters of exposed women had fewer live births (1.6) than the unexposed (1.9) (P = 0.005). CONCLUSIONS The high risk of reproductive dysfunction seen in women exposed to DES in utero was not observed in their daughters, but most women in our cohort have not yet attempted to start their families, and further follow-up is needed to assess their reproductive health. Our findings of menstrual irregularity and possible infertility in third-generation women are preliminary but compatible with speculation regarding transgenerational transmission of DES-related epigenetic alterations in humans.

UI	MeSH Term	Description	Entries
D007247	Infertility, Female	Diminished or absent ability of a female to achieve conception.	Sterility, Female,Sterility, Postpartum,Sub-Fertility, Female,Subfertility, Female,Female Infertility,Female Sterility,Female Sub-Fertility,Female Subfertility,Postpartum Sterility,Sub Fertility, Female
D008599	Menstruation Disturbances	Variations of MENSTRUATION which may be indicative of disease.	Hypomenorrhea,Menstruation Disorders,Menstruation, Retrograde,Polymenorrhea,Irregular Menses,Irregular Menstruation,Menstrual Irregularities,Menstrual Irregularity,Disorder, Menstruation,Disorders, Menstruation,Disturbance, Menstruation,Disturbances, Menstruation,Irregularity, Menstrual,Menses, Irregular,Menstruation Disorder,Menstruation Disturbance,Menstruation, Irregular,Retrograde Menstruation
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011297	Prenatal Exposure Delayed Effects	The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH.	Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D004054	Diethylstilbestrol	A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)	Stilbestrol,Agostilben,Apstil,Diethylstilbestrol, (Z)-Isomer,Diethylstilbestrol, Disodium Salt,Distilbène,Stilbene Estrogen,Tampovagan,Estrogen, Stilbene
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D012306	Risk	The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome.	Relative Risk,Relative Risks,Risk, Relative,Risks,Risks, Relative
D016016	Proportional Hazards Models	Statistical models used in survival analysis that assert that the effect of the study factors on the hazard rate in the study population is multiplicative and does not change over time.	Cox Model,Cox Proportional Hazards Model,Hazard Model,Hazards Model,Hazards Models,Models, Proportional Hazards,Proportional Hazard Model,Proportional Hazards Model,Cox Models,Cox Proportional Hazards Models,Hazard Models,Proportional Hazard Models,Hazard Model, Proportional,Hazard Models, Proportional,Hazards Model, Proportional,Hazards Models, Proportional,Model, Cox,Model, Hazard,Model, Hazards,Model, Proportional Hazard,Model, Proportional Hazards,Models, Cox,Models, Hazard,Models, Hazards,Models, Proportional Hazard