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Br J Cancer. 1993 Mar;67(3):635-7.

Female hormone utilisation and risk of hepatocellular carcinoma.

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Istituto di Recherche Farmacologiche Mario Negri, Milano, Italy.


The relationship between female hormone use and primary liver cancer was analysed using data from a case-control study conducted between 1984 and 1992 in Milan on 82 female incident cases with histologically or serologically confirmed hepatocellular carcinoma and 368 controls admitted to hospital for acute non-neoplastic, non-hormone-related diseases. An elevated relative risk (RR) or primary liver cancer was observed in oral contraceptive (OC) users (RR 2.6, for ever versus never users, 95% confidence interval, CI 1.0-7.0). The RR was directly related to duration of use (RR 1.5 for < or = 5 years and 3.9 for > 5 years) and persisted for longer than 10 years after stopping use (RR 4.3%, 95% CI 1.0-18.2). The RR were below unity, although not significantly, for women ever using oestrogen replacement therapy (RR 0.2, 95% CI 0.03-1.5) and female hormones for indications other than contraception and menopausal therapy (RR 0.4, 95% CI 0.1-1.5). The long-lasting, association between risk of hepatocellular carcinoma and OC use has potential implications on a public health scale, since primary liver cancer is a relatively rare disease among young women, but much more common at older ages. This study provides limited but reassuring evidence on the possible relationship between oestrogen replacement treatment and subsequent risk of hepatocellular carcinoma.


Health professionals at a network of teaching and general hospitals in the greater Milan area in Italy compared data on 43 35-59 year old female patients who had confirmed primary liver cancer with data on 194 26-59 year old females patients hospitalized for nonneoplastic diseases to quantify the risk of oral contraceptive (OC) use. They examined duration of use and time since last use. They also wanted to examine female hormone use for menopausal therapy and for indications other than contraception and menopausal therapy. 9 (21%) liver cancer patients and 21 (11%) controls has ever used OCs. The overall relative risk (RR) for primary liver cancer was 2.6. Women who had used OCs for at least 5 years had an RR of 3.9, while those who had used them for less than 5 years had an RR of 1.5. The RR of women who had taken OCs within the last 10 years was 1.1, but was considerably higher (4.3) for those women who had not taken OCs for over 10 years. Women who had ever undergone estrogen replacement therapy and used female hormones for indications other than menopausal therapy and contraception had lower RRs of acquiring primary liver cancer than those who had never used these hormones (0.2 and 0.4, respectively), but the RRs were not significant. A long-lasting increased risk of primary liver cancer in OC users raises public health concern, especially for older women. It appears that estrogen replacement therapy may reduce the risk of acquiring liver cancer.

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