Reproductive
Menstrual and reproductive outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): An updated report from the National Cancer Institute (NCI) DES Third Generation Study Stephanie Ho* Stephanie Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho NIH/NCI
Background
Diethylstilbestrol (DES), a human carcinogen, was used from the 1940s-70s for women at risk of miscarriage. Adverse health effects have been well documented in women who were given DES during pregnancy and their exposed children. Within the NCI DES Third Generation Study, we followed daughters of prenatally exposed and unexposed women to study menstrual and reproductive outcomes in the third generation.
Methods
In 2000, daughters of women who were prenatally exposed or unexposed to DES in the U.S. were identified through their mothers’ parity records; daughters were eligible for study enrollment at age 18. Baseline (n=964 exposed, 529 unexposed) and up to 2 follow-up questionnaires (n=839 exposed, 585 unexposed) were administered from 2001-2019. We estimated prevalence ratios (PRs) and 95% CIs for menstrual and reproductive outcomes associated with DES exposure by age groups (18-<20;20-<30;30-<40;40-<50;50-59), using log-binomial regression models. Repeated questionnaires from the same woman were accommodated via a robust variance estimate.
Results
Compared with daughters of unexposed women, daughters of prenatally DES-exposed women had increased prevalence of irregular menstrual cycles, notably at age 18-<20 (PR=1.82, 95% CI:1.05-3.15). Among women age 20-<30, DES exposure was associated with decreased prevalence of ever being pregnant (PR=0.81, 95% CI:0.67-0.99). Among women age 30-<40, DES exposure was related to increased prevalence of amenorrhea, defined as lack of menstruation for >6 weeks (PR=1.29, 95% CI:1.03-1.61).
Conclusions
Continued follow-up of women whose mothers were prenatally exposed to DES suggests they may be at an increased risk for adverse menstrual outcomes. Decreased pregnancy prevalence in exposed women may signal an effect of DES on infertility; analyses with more direct measures of infertility are ongoing. We plan to study the association of DES and menopause and whether effects differ by DES dose.