The association of oral contraceptive use with liver cancer was examined in a study of 76 deaths from primary liver cancer, 22 deaths from cancer of the intrahepatic bile ducts, and 629 controls among women aged 25 to 49 years. The subjects in the study are from the 1986 National Mortality Followback Survey, which included a questionnaire sent or administered to the next-of-kin of almost 20,000 deceased individuals in the United States. Information on a number of lifestyle factors was collected, including questions on oral contraceptive use. Increased risks of primary liver cancer were found for ever-users (odds ratio [OR]=1.6, 95 percent confidence interval [CI]=0.9–2.6), and for long-term (≥10 years) users (OR=2.0, CI=0.8–4.8) of oral contraceptives. When the analysis was restricted to subjects whose spouse or parent was the respondent, more pronounced risks were seen for ever-users (OR=2.7, CI=1.4–5.3) and long-term users (OR=4.8, CI=1.7–14.0). No clear excess risk was found for cancer of the intrahepatic bile ducts. This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Higashi S, Tomita T, Mizumoto R, Nakakuki K. Development of hepatoma in rats following oral administration of synthetic estrogen and progestogen. Gann 1980; 71: 576–7.
Baum JK, Holts F, Bookstein JJ, Klein EW. Possible association between hepatomas and oral contraceptives. Lancet 1973; ii: 926–9.
Scott LD, Katz AR, Duke JH. Oral contraceptives, pregnancy, and focal nodular hyperplasia of the liver. JAMA 1984; 251: 1461–3.
O'Sullivan JP, Rosswick RP. Oral contraceptives and malignant hepatic tumors. Lancet 1976; i: 1124–5.
Tigano F, Ferlazzo B, Barrille A. Oral contraceptives and malignant hepatoma. Lancet 1976; ii: 196.
Henderson B, Preston-Martin S, Edmonson HA, Peters RL, Pike MC. Hepatocellular carcinoma and oral contraceptives. Br J Cancer 1983; 48: 437–40.
Neuberger J, Forman D, Doll R, Williams R. Oral contraceptives and hepatocellular carcinoma. Br J Cancer 1986; 292: 1355–7.
Forman D, Vincent TJ, Doll R. Cancer of the liver and the use of oral contraceptives. Br J Cancer 1986; 292: 1357–61.
Palmer JL, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, Shapiro S. Oral contraceptive use and liver cancer. Am J Epidemiol 1989; 130: 878–82.
La Vecchia C, Negri E, Parazzini F. Oral contraceptives and primary liver cancer. Br J Cancer 1989; 59: 460–1.
Vall Mayans M, Calvet X, Bruix J, et al. Risk factors for hepatocellular carcinoma in Catalonia, Spain. Int J Cancer 1990; 46: 378–81.
Prentice RL. Epidemiologic data on exogenous hormones and hepatocellular carcinoma and selected other cancers. Prev Med 1991; 20: 38–46.
The WHO collaborative study of neoplasia and steroid contraceptives. Combined oral contraceptives and liver cancer. Int J Cancer 1989; 43: 254–9.
Kew MC, Song E, Mohammed A, Hodkinson J. Contraceptive steroids as a risk factor for hepatocellular carcinoma: a case/control study in South African black women. Hepatology 1990; 11: 298–302.
Dawson DA. Trends in use of oral contraceptives—data from the 1987 National Health Interview Survey. Fam Plann Perspect 1990; 22: 169–72.
Seeman A, Poe G, McLaughlin JK. Design of the 1986 National Mortality Followback Survey: considerations on collection data on decedents. Public Health Rep 1989; 104: 183–8.
Breslow NE, Day NE. Statistical Methods in Cancer Research. Volume 1. The Analysis of Case-Control Studies. Lyon, France: International Agency for Research on Cancer, 1980; IARC Sci. Pub. No. 32.
McQuillan GM, Townsend TR, Field HA, Carroll M, Leahy M, Polk BF. Seroepidemiology of hepatitis B virus infection in the United States 1976 to 1980. Am J Med 1989; 87: 5–10.
Glass R, Johnson B, Vessey M. Accuracy of recall of histories of oral contraceptive use. Br J Prev Soc Med 1974; 28: 273–5.
Thorogood M, Vessey M. The reliability of surrogate information about oral contraceptive use, smoking, height and weight collected from men about their wives. Contraception 1989; 39: 401–8.
Percy C, Ries LG, Van Holten VD. The accuracy of liver cancer as the underlying cause of death on death certificates. Public Health Rep 1990; 105: 361–7.
International Agency for Research on Cancer. Alcohol Drinking. Lyon, France: IARC, 1988; Monogr Eval Carcinog Risk Chem Humans, Vol. 44: 208–12.
Trichopoulos D, MacMahon B, sparros L, Merikas G. Smoking and hepatitis B-negative primary hepatocellular carcinoma. JNCI 1980; 65: 111–4.
Hsing AW, McLaughlin JK, Hrubec Z, Blot WJ, Fraumeni JFJr. Cigarette smoking and liver cancer among US veterans. Cancer Causes Control 1990; 1: 217–21.
Hartz SC, Shapiro S, Kaufman DW, Rosenberg L, Slone D. Factors associated with oral contraceptive use. AJPH 1980; 70: 1105–8.
McLaughlin JK, Blot WJ, Mehl ES, Mandel JS. Problems in the use of dead controls in case-control studies: I. General results. Am J Epidemiol 1985; 121: 131–9.
McLaughlin JK, Blot WJ, Mehl ES, Mandel JS. Problems in the use of dead controls in case-control studies: II. Effect of excluding certain causes of death. Am J Epidemiol 1985; 122: 485–94.
Yager JD, Yager R. Oral contraceptive steroids as promoters of hepatocarcinogenesis in female Sprague-Dawley rats. Cancer Res 1980; 40: 3680–5.
Valla D, Benhamou J. Liver diseases related to oral contraceptives. Dig Dis 1988; 6: 76–87.
Edmonson HA, Reynolds TB, Henderson B, Benton B. Regression of liver cell adenomas associated with oral contraceptives. Ann Intern Med 1977; 86: 180–2.
Tao LC. Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma. Cancer 1991; 68: 341–7.
Nagasue N, Ito A, Yukaya H, Ogawa Y. Estrogen receptors in hepatocellular carcinoma. Cancer 1986; 57: 87–91.
Duffy MJ, Duffy GJ. Estradiol receptors in human liver. J Steroid Biochem 1978; 9: 233–5.
International Agency for Research on Cancer. Overall Evaluation of Carcinogenicity: an Updating of IARC Monographs Vols 1 to 42. Lyon, France: IARC, 1987; IARC Mongr Suppl, Vol 7: 297–308.
Authors are with the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, with the exception of Mr Co-Chion who is at Westat Inc., Rockville, MD, USA. Address reprint requests to Dr Hsing at the National Cancer Institute, Executive Plaza North, Room 415, Bethesda, MD 20892, USA.
About this article
Cite this article
Hsing, A.W., Hoover, R.N., McLaughlin, J.K. et al. Oral contraceptives and primary liver cancer among young women. Cancer Causes Control 3, 43–48 (1992). https://doi.org/10.1007/BF00051911
- Case-control study
- liver cancer
- oral contraceptive use
- United States