Oral contraceptive estrogen content and adverse effects: has a dose-response relationship been established?
It is widely assumed that oral contraceptives (OCs) containing 30-35 mcg of estrogen carry a lower risk of adverse health effects than the OCs initially prescribed that contained 50 mcg of estrogen. Canadian physicians are urged to prescribe the lowest dose of estrogen possible that will provide cycle control. Lacking however is strong scientific evidence that the newer low-dose OCs are any safer than OCs with a high estrogen content. The 14 epidemiologic studies published to date that have explored the relationship between estrogen dose and side effects such as venous thromboembolism arterial thromboembolism hypertension and gallbladder disease have produced inconsistent findings and contained many biases. Studies of OC effects are made difficult by the short time period in which low-dose OCs have been on the market and the lack of standardized methods for comparing the potencies of the progestogen component of OCs. A perennial source of bias in these studies is the spurious dose response association in older women who are inherently at greater risk of disease processes because of age factors. Many studies fail to control for cigarette smoking an important confounding factor in thromboembolic disease. It must also be considered that admission for the investigation of possible OC-related conditions may be biased toward women using a higher-dose OC because of an increased index of suspicion in such cases. Overall a review of the literature suggests that the existence of a dose-response relationship between the OCs estrogen content and adverse health effects is uncertain at best. While a low-dose OC is recommended for the majority of women physicians should not hesitate to prescribe high-dose pills to women who are on antibiotics or may forget to take the pill or discontinue its use if spotting occurs.