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International Agency for Research on Cancer (IARC) - Summaries & Evaluations

ORAL CONTRACEPTIVES, SEQUENTIAL
(Group 1)

For definition of Groups, see Preamble Evaluation.

Supplement 7: (1987) (p. 296)

A. Evidence for carcinogenicity to humans (sufficient)

Case reports of endometrial cancer occurring at an unusually young age in users of sequential oral contraceptives provide evidence that these preparations can cause endometrial cancer [ref: 1]. Three case-control studies have provided the following estimates of the relative risk (and 95% confidence intervals) for endometrial cancer in women who had used sequential oral contraceptives: 2.2 (0.6-7.3) [ref: 2], 2.1 (0.8-5.8) [ref: 3] and [1.9 (0.7-5.3)] [ref: 4]. One study [ref: 2] showed a relative risk of 7.3 (1.4-38.8) in users of a preparation that contained a relatively large amount of a potent oestrogen (0.1 mg ethinyloestradiol) and only a weak progestin (25 mg dimethisterone); another [ref: 4] showed a relative risk of 4.6 in users of more than two years' duration. The finding of an increased risk for endometrial cancer in relation to sequential oral contraceptives is in contrast with a reduction in risk for endometrial cancer found in association with the use of combined oral contraceptives.

B. Evidence for carcinogenicity to animals (inadequate for dimethisterone in combination with ethinyloestradiol)

Dimethisterone and oestrogen

When dimethisterone and ethinyloestradiol were given sequentially to female dogs by oral administration, a few palpable mammary nodules were reported to have occurred in treated (4/16) and in untreated animals (2/16) [ref: 5].

C. Other relevant data

No adequate data were available on the genetic and related effects of sequential oral contraceptives in humans. See, however, the summaries of data on individual compounds commonly found in sequential oral contraceptives: chlormadinone acetate, dimethistereone, ethinyloestradiol and mestranol.

Overall evaluation

Sequential oral contraceptives are carcinogenic to humans (Group 1).

For definition of the italicized terms, see Preamble Evaluation.

Also previous evaluations: Vol. 6 (1974); Vol. 21 (1979)

References

1. IARC Monographs, 21, 111-112, 133, 1979

2. Weiss, N.S. & Sayvetz, T.A. (1980) Incidence of endometrial cancer in relation to the use of oral contraceptives. New Engl. J. Med., 302, 551-554

3. Centers for Disease Control Cancer and Steroid Hormone Study (1983) Oral contraceptive use and the risk of endometrial cancer. J. Am. med. Assoc., 249, 1600-1604

4. Henderson, B.E., Casagrande, J.T., Pike, M.C., Mack, T., Rosario, I. & Duke, A. (1983) The epidemiology of endometrial cancer in young women. Br. J. Cancer, 47, 749-756

5. IARC Monographs, 21, 233-255, 377-385, 1979


Last updated: 10 February 1998






















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