To the Editor.—
The development of neoplasms of the liver in women using oral contraceptives1 could have been anticipated had results of tests in animals received more consideration. In 1966, a British pathologist reported to the Committee on Safety of Medicines in Great Britain "various stages of nodular hyperplasia and the production of hepatoma" in livers of rats that had received mestranol.2 Results of additional tests in rats and mice of several synthetic estrogens and progestins, singly and in combinations commonly used in oral contraceptives, were reported to the committee in 1972.2 Neoplasms were observed in livers in as many as 32% of male rats that received norethynodrel, in 23% that received a combination of norethisterone and mestranol, and in 17% given ethinyl estradiol. Despite these findings, the committee concluded that "the extensive tests... do not support the previous work showing liver damage progressing to nodular hyperplasia
Lingeman CH. Evaluating Carcinogenicity of Oral Contraceptives. JAMA. 1976;236(15):1690. doi:10.1001/jama.1976.03270160014004
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