Adverse effects of preventive therapy in humans.
The main adverse effects of tamoxifen, aspirin, oral contraceptives (OCs) and retinoids used as chemopreventive agents in humans are reviewed and quantified here. With regard to tamoxifen, there are suggestions of some excess risk of liver, and perhaps gastrointestinal, cancers. The public health impact of such associations, if any, is still unclear. Tamoxifen use is associated with endometrial and myometrial hyperplasia. Data from five studies based on 174 cases indicate that the overall relative risk (RR) of endometrial cancer in ever tamoxifen users is 1.73 (95% confidence interval = 1.1-2.6). However, there is a significant difference between the results of American and European studies, so the relationship between tamoxifen and endometrial cancer remains open to debate. The major side-effect of aspirin is gastrointestinal lesions; the risk of these is increased two- to tenfold, depending on the dose. Aspirin is also associated with an increased risk of haemorrhagic stroke, although its protection against other types of stroke and against myocardial infarction leads to a favourable pattern of risk for all cardiovascular conditions. Short-term side-effects of OCs include vascular diseases and a moderately increased risk of breast cancer. The RR of cervical cancer and hepatocellular carcinoma are also increased in OC users, although the public health impact of such associations is small. Toxicity associated with retinoid treatment is rarely serious as most effects observed are reversible on stopping use. Side-effects include changes in the skin and mucous membranes (dry skin, hair loss, dry nose, conjunctivitis), musculoskeletal symptoms, ophthalmological effects, changes in transaminase activity, changes in clinical chemistry markers (increase in serum triglycerides and decrease in high-density lipoproteins) and, rarely, central nervous system effects. A serious toxicological aspect of retinoid treatment is teratogenesis; its use should therefore be avoided in women with childbearing potential, and, in cases of use, conception should be delayed for a long time after stopping treatment. Thus, when considering side-effects of chemoprevention, the major issues of concern are the rare long-term effects (chiefly neoplasms), and the need for more precise overall risk-and cost-benefit assessment, particularly for healthy people.
La Vecchia
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C
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Tavani
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A
Garattini
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S
D016588:Anticarcinogenic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D003276:Contraceptives, Oral / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control; D012176:Retinoids / Q000009:adverse effects / Q000627:therapeutic use; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D003276:Contraceptives, Oral; D012176:Retinoids; D013629:Tamoxifen; D001241:Aspirin