Exogenous Estrogens and Endometrial Cancer: A Case-Control Study and Assessment of Potential Biases

Abstract

Eighty-eight cases with newly diagnosed carcinoma of the endometrium and 177 age-matched neighborhood controls were interviewed to test the hypothesis that exogenous estrogens lead to an increased risk of endometrial cancer. Forth-five per cent of the cases and 22% of the controls reported a history of estrogen use which yielded an odds ratio of 2.9 (confidence interval (Cl) 1.7-5.1). Women with five or more years of estrogen use had an odds ratio of 8.6 (Cl 3.2-23.0). Approximately 80% of the estrogen users had used conjugated equine estrogens. For these women the odds ratio was 4.0 (Cl 1.9-8.4) for daily dosages of more than 1 mg of estrogen. Several sources of bias which might affect the estrogen association were investigated. These included comparability of cases and controls, selection procedures, difference between estrogen users and nonusers, exclusion of controls who had hysterectomy, source of estrogen information, and differential recall. The concept or medical surveillance was evaluated by access to medical care and prior history of dilatation and curettage. The strong association between exogenous estrogen use and endometrial cancer remained after consideration for the effects of these biases.

Risk factors of female cancers in ragusa population (sicily) - I. Endometrium and cervix uteri cancers

“…With respect to oestrogen replacement therapy, the results of present study are comparable to those of others (14,28), in that women who use these drugs show an elevated risk of endometrial cancer. Although the frequency of oestrogen users was quite similar to that found in another study conducted in Italy (17) (27% among cases and 12% among controls), the shorter length of oestrogen use (mean 13 months among cases and 16 among controls) does not allow assessment of the relationship between length of use and magnitude of risk.…”

Menstrual and Reproductive Factors and Fracture Risk: The Leisure World Cohort Study

“…[58][59][60] Several studies have compared self-reports of menopausal estrogen use with physician/pharmacy records, 56,60-67 and most have shown moderate to good agreement on ever/never use. 56,[60][61][62]64,67 Two studies evaluated age at first replacement estrogen; agreement was 58% within 3 years in one 64 and 53% within 2 years for the other. 66 Similar to age at menopause, misclassification of the timing and duration of menopausal hormone exposure is more likely for women who are older and naturally menopausal and whose last use was a distant event.…”

Comparison of questionnaire information and pharmacy data on drug use

“…Most studies focused on reproduction-related drug use, like oral contraceptives [2], estrogen use [3] and pregnancyrelated drug use [4]. Very few studies have evaluated non-hormonal or non-pregnancy-related medication [5 6].…”