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The human ovarian carcinoma cell line NIH-OVCAR-3 grown in immunodeficient mice has been reported to be sensitive to estrogen medications and to express progestin receptor. To assess the effects of sex steroids on CA 125 production and survival times in these mice, we administered Tamoxifen, estrogen, and progestin. During the first 28 days after inoculation of mice with 2.3 million tumor cells ip, serum CA 125 rose exponentially, reaching 4308 +/- 776 and 3905 +/- 1013 units/ml (mean +/- SEM, P greater than 0.1) in placebo- and Tamoxifen-treated mice, respectively; median survival times were 41 and 39 days, respectively (P greater than 0.1). Uninoculated mice had nondetectable CA 125, and all outlived the inoculated mice. In tumor-inoculated mice, serum CA 125 levels and survival were similar when estrogen or progestin was injected alone and when both were given in combination. We detected no significant differences in production of CA 125 in vitro by tumor cells harvested from ascites fluid when the mice were treated with placebo, estrogen, or progestin. We conclude that, for our model, serial measurements of serum CA 125 provide excellent estimates of the relationship between tumor burden and survival, and that CA 125 production appears unaffected by estrogen, progestin, or Tamoxifen.

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Factors related to the risk of developing clear cell adenocarcinoma in diethylstilbestrol-exposed women were investigated in 156 patients in the United States with clear cell adenocarcinoma and documented diethylstilbestrol exposure (Registry cases) and 1848 diethylstilbestrol-exposed women of similar age without cancer (National Cooperative Diethylstilbestrol Adenosis Project). Diethylstilbestrol dosage patterns, the use of other hormones, mother's age and pregnancy history, and daughter's birth month, birth weight, and age at menarche were compared. The relative risk was higher for those whose mothers began diethylstilbestrol before the twelfth week of pregnancy and for those who were born in the fall (winter conception). Maternal history of at least one prior spontaneous abortion elevated the risk. Supportive evidence for the difference in birth month distribution was also found by a comparison with United States vital statistics. Each factor was confirmed to be significant in a multivariate logistic model that examined all of them with region and year of birth adjusted.

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Twenty-eight black females with clear cell adenocarcinoma of the vagina and cervix have been accessioned in the Registry for Research on Hormonal Transplacental Carcinogenesis. Most were born in the southern United States and histories of prenatal exposure to diethylstilbestrol were less frequent than with white patients. The characteristics of these cases were similar to those among whites in stage, variety of cell type, and patient survival.

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Information on reproductive history, gynecologic operations, and examinations was analyzed for 338 diethylstilbestrol (DES)-exposed and 298 unexposed women whose mothers participated in an evaluation of DES use in pregnancy 28 years ago. A history of infrequent menses (less often than every 36 days) was reported more commonly by the exposed women (32%) than by the unexposed women (15%) and the mean duration of menstrual flow was also less. A greater number of exposed women than unexposed women experienced primary infertility (53 versus 19). The reasons for these differences are not currently known. Comparison of the outcomes of first pregnancies showed a higher proportion of premature births, spontaneous abortions, and ectopic pregnancies in the exposed women (P less than 0.001). The difference in the occurrence of ectopic pregnancies was statistically significant (8 versus 0; P less than 0.005). An adverse pregnancy outcome was more likely in DES-exposed women with cervicovaginal ridges. However, when the outcome of all pregnancies were considered, 81% of the exposed women had at least one living child. More exposed women than unexposed women had gynecologic surgical procedures, which may, in part, be due to the increased medical surveillance of the exposed group. The spectrum of diseases at operation in both groups was similar. Adnexal masses and pelvic inflammatory disease were more commonly reported among the exposed women while the occurrence of endometriosis in both groups was similar. For the exposed women who had been examined at the Chicago Lying-In Hospital over a 4-year period, epithelial changes in the vagina had disappeared in 32% and cervicovaginal ridges had disappeared in 57%.

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Reproductive histories were compared for 226 DES-exposed and 203 -unexposed daughters whose mothers participated in a double-blind evaluation 27 years before. Irregular menstruation was slightly more common among the exposed (10%) than among the unexposed (4%). Nineteen of the exposed and only four of the unexposed had primary infertility. Among those at risk, 86% of the unexposed and 67% of the exposed had become pregnant. The reasons for these differences are not known. Comparison of evaluable first pregnancy outcome revealed full-term live birth to be more common among the unexposed (85%) than the exposed (47%). Premature live birth was experienced by 22% of the exposed but only 7% of the unexposed. Nonviable outcomes of stillbirth, neonatal death, miscarriage and ectopic pregnancy occurred in 31% of the exposed and 8% of the unexposed. The difference in pregnancy outcomes between the groups is highly significant. The DES-exposed with transverse cervicovaginal ridges were more likely to experience a nonviable outcome. Overall 82% of the exposed and 93% of the unexposed had at least one live offspring.

PIP: Reproductive histories were compared for 226 diethylstilbestrol (DES) exposed and 203 unexposed daughters whose mothers participated in a double-blind evaluation 27 years earlier. Complete prenatal medication records were available for 389 DES exposed and 395 unexposed daughters from the original study. Interviews were conducted from January 1978 to August 1979 at the time of follow-up gynecologic visits or by telephone or mail for those unable to come for an examination. Irregular menstruation was slightly more common among the exposed (10%) than among the unexposed (4%). 19 of the exposed and 4 of the unexposed had primary infertility. Among those at risk, 86% of the unexposed and 67% of the exposed had become pregnant; the reasons for these differences are unknown. Comparison of evaluable 1st pregnancy outcome revealed full-term live birth to be more common among the unexposed (85%) than the exposed (47%). Premature live birth was experienced by 22% of the exposed and 7% of the unexposed. Non-viable outcomes of stillbirth, neonatal death, miscarriage and ectopic pregnancy occurred in 31% of the exposed and 8% of the unexposed. The difference in pregnancy outcomes between the exposed and the unexposed groups is highly significant. The DES-exposed with transverse cervicovaginal ridges were more likely to experience a non-viable outcome. 82% of the exposed and 93% of the unexposed had at least 1 live offspring.

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