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Oral contraceptives and neoplasia.


 Cancer is the presumed complication of oral contraceptive (OC) use that is of greatest concern to the public, although with the exception of cancer of the endometrium, which was linked to 1 specific type of sequential preparation, Oracon, there is no convincing evidence linking OCs and cancer. Oracon was found in detailed study to be strongly associated with subsequent risk for cancer, while other sequentials and combination pills were found to reduce the risks. Oracon was different from other sequentials in that it contained a large amount of estrogen, 100 mcg of ethinyl estradiol, with only a weak progestin, 25 mg of dimethisterone, too little to reverse estrogen-induced endometrial hyperplasia. Proctection appears to increase with duration of use of combined OCs. The Centers for Disease Control (CDC) estimates that approximately 2000 cases of endometrial cancer are prevented each year in the US due to the present level of OC use. Evidence is strong that OCs are a means of preventing ovarian cancer, the 4th leading cause of cancer deaths among women in the US. Case-control studies show that women with ovarian cancer are less likely to have used OCs than are controls without cancer. Physiologically, the risk for cancer of the ovary seems to be related to what has been described as "incessant ovulation". Until recently, most women throughout history have been either pregnant or lactating for most of the time. Time spent pregnant or on OCs, with resulting blockage of ovulation, is now established as protective against ovarian cancer. The longer a women has been taking OCs, the greater the protection. Researchers at the CDC estimate that 1700 ovarian cancer deaths are prevented each year in the US by the use of OCs. Results of epidemiologic studies exploring the connection between OC use and cervical cancer are incolclusive because of methodological problems of preventing bias and controlling for confounding variables. Women taking OCs are more likely to have regular cervical cytology, giving rise to selection bias. Use of women emloying barrier contraception as a control group is another source of bias because barrier contraceptives reduce the rise of cervical neoplasia. Sexual behavior, especially age at onset of sexual activity and number of partners over time, is an important determinant of cervical cancer risk and therefore an inportant confounder that is difficult to control. On balance, there appears to be no or very little increased risk of cervical cancer from OC use; given the confounding factors, a final answer may never be obtained. The risk of developing hepatocellular adenoma is about 30 cases/million women per year.
