For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p.280)
A. Evidence for carcinogenicity to humans (sufficient)
A number of studies, utilizing a variety of designs, have shown a consistent, strongly positive association between exposure to a number of oestrogenic substances and risk of endometrial cancer, with evidence of positive dose-response relationships both for strength of medication and duration of use [ref: 1]. Consistent findings have also been seen in more recent studies [ref: 2-16]. The rise and fall of incidence of endometrial cancer in several areas of the USA was compatible with trends in oestrogen use [ref: 1,15].
Of the 20 epidemiological studies of oestrogen replacement therapy and breast cancer risk [ref: 16-35], nine show a positive relation between oestrogen use and breast cancer [ref: 17-20,22-24,28,33]. The increased risks tend to be small; for example, a 50% increase was found with 20 years of menopausal oestrogen replacement therapy use [ref: 24]. All except one [ref: 33] of the positive studies involved use of population controls (eight of the nine studies with population controls gave positive results), and most showed increased risk after prolonged use or after ten or more years since initial exposure. One study showed a positive association with current oestrogen use [ref: 28].
One possible reason that studies with hospital controls gave negative results and those with population controls positive results is that oestrogen replacement therapy may be used more frequently in hospitalized women than in the general population. However, in two studies involving use of both hospital and population control groups, one giving positive [ref: 29] and the other largely negative [ref: 25] results, similar results were obtained when hospital and population controls were used to estimate the relative risk. Three of the studies with negative results [ref: 26,27,34] probably did not permit the authors to address satisfactorily the question of long-term use of oestrogen replacement therapy. The large hospital-based study that showed a positive finding used as controls subjects with a large spectrum of acute conditions unrelated to any of the known or suspected risk factors for breast cancer [ref: 33].
One cohort study of 1439 women initially treated for benign breast disease showed increased risk for women who took exogenous oestrogens after biopsy, but not for those who had taken them before biopsy. The increased risk in the former group appeared to be associated with epithelial hyperplasia or calcification in the initial lesion [ref: 35].
Overall evaluation
Oestrogen replacement therapy is carcinogenic to humans (Group 1).
For definition of the italicized terms, see Preamble Evaluation.
Also previous evaluations: Vol. 6 (1974); Vol. 21 (1979)
Subsequent evaluation: Vol. 72 (1999)
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See Also:
Toxicological Abbreviations