Oral contraceptives and neoplasia

Combined estrogen-progestogen oral contraceptives have been available in the United States since 1960. The first compound approved contained 10 mg of norethynodrel and 150 μg of mestranol. Current estimates of worldwide use range from 54 million to over 80 million and in the United States use is estimated at 8 million to over 10 million women. Clearly, to justify such wide use of potent drugs, the risk-benefit ratio must weigh substantially in favor of the drug benefits. In the past 19 years over 30 brands of combined oral contraceptives have been sold in the United States. Today, they contain one of five synthetic progestogens (all derived from 19-nortestosterone) and one of two estrogens. Most women are now using combined oral contraceptives with 0.3 to 1 mg of progestogen and 20 to 50 μg of estrogen. Since 1970 all of the newly introduced compounds have used ethinylestradiol as the estrogen fraction, and all but one have used norethindrone as the progestogen. One compound contains 0.3 mg of norgestrel. Outside the United States some of the 17α-hydroxyprogesterone derivatives are in use. However, these derivatives were withdrawn from the United States market in response to concerns regarding the occurrence of neoplastic lesions in dogs. Few issues evoke as much concern and controversy as does the suspected association between oral contraceptive use and the development of cancer. Isolated case reports and preliminary findings may give rise to overwhelming pressure to discontinue use of the drug with little attempt to weigh its possible risk-benefit ratios. This response is not confined to human evidence. Suspicion of carcinogenicity in any animal species has raised similar concerns and evoked the same demand for drug withdrawal. Other serious side effects such as cardiovascular problems with use of the oral contraceptives and severe pelvic infections with use of intrauterine devices have extensive documentation. Morbidity and mortality rates have been estimated. By and large the response of the public and the medical profession has been to evaluate the risk-benefit ratio to contraceptive therapy as related to unplanned pregnancy or induced abortion and to accept the much lower risk of these very effective methods of contraception. The authors survey some of the available data and attempt to evaluate possible association between oral contraceptives and human neoplasia in light of pregnancy risk of benefit or oral contraception.