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  • Title: Combined oral contraceptives: risks and benefits.
    Author: Thorogood M, Villard-Mackintosh L.
    Journal: Br Med Bull; 1993 Jan; 49(1):124-39. PubMed ID: 8324603.
    Abstract:
    By the age of 25 years, more than 95% of sexually active women have been exposed to combined oral contraceptives (COCs). Any effects associated with their use, therefore, carry important public health implications. COCs exert major protective effects against ovarian and endometrial cancer, which continue many years after cessation of use. COCs increase the risk of cardiovascular disease, but this risk is probably confined to current users. It is unclear whether lower dose preparations carry less risk. The precise relationship between COC use and risk of breast and cervical cancer is uncertain, although it is clear that COCs do not influence the overall risk of breast cancer. The risk-benefit equation for COC use depends crucially on assumptions about the true breast cancer risk. If there is no increased risk then COCs have a net beneficial effect on mortality, mainly due to the saving in ovarian cancer deaths. However, with more pessimistic assumptions about breast cancer, COCs have an adverse effect. The risk-benefit equation will vary for individual women. Most research has related to the developed world and extrapolation of findings to developing countries is inappropriate. The evidence of the effects of combined oral contraceptives (COCs) on mortality and morbidity is reviewed. All the 11 case-control studies published since 1980 reported and approximate halving of endometrial cancer risk among COC users. The CASH study showed that the protective effect was apparent after 12 months' use, and users had 40% of the risk of non-users after 2 years' use. A study showed that 5 patterns of self-perceived prolonged, heavy, frequent, irregular, or painful bleeding during menstruation were reported less frequently in COC users than in users of other methods. Benign breast disease is rarer, and functional ovarian cysts are less frequent in COC users. Lower-dose preparations may carry a lower risk of myocardial infarction. Smoking possibly potentiates the risk associated with oral contraceptive (OC) use, and it is a major risk factor for myocardial infarction. The Oxford/FPA study found a 2-3-fold increase in incidence of non-haemorrhagic stroke among current OC users. The epidemiologic data on the current risk of venous thromboembolism in relation to OC use are equivocal. New lower dose COCs have a smaller adverse effect on the lipid profile: they cause a smaller increase in low density lipoprotein cholesterol (LDL) and a variable but smaller decrease in high density lipoprotein cholesterol (HDL). The large CASH study, based on 2088 cases, found a significantly elevated relative risk (2.7) of breast cancer, but only in women who had used the OC for at least 11 years. Of 6 case-control studies of hepatocellular carcinoma and OC use published since 1983, all but one showed a large elevated relative risk of around 4-fold. Delayed return of fertility has been observed in nulliparous women 30 who had 2 years; continuous exposure to COCs, although this may not be associated with low-dose, modern OCs. Malignant melanoma, pituitary adenoma, gallbladder disease, and chronic inflammatory bowel disease have been possibly associated with adverse side effects, but results are so far inconclusive.
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