The evolution of combined oral contraception: improving the risk-to-benefit ratio.

Since its introduction in 1960, the combined oral contraceptive (COC) pill has become one of the most widely and frequently used methods of contraception worldwide. Although highly effective, early COC formulations were associated with significant adverse effects and unacceptable cardiovascular risk. Improvements in tolerability and safety have been achieved, without compromises in effectiveness, primarily via hormone dosage reductions and the development of several new progestins. Multiphasic COCs and extended-/continuous-cycle COCs have also been introduced, although the clinical advantages of these formulations vs. traditional COCs have yet to be established. Inclusion of natural estrogens such as estradiol valerate and 17β-estradiol with selective progestins in new combinations that maintain good cycle control is the most recent evolutionary step designed to improve COC tolerability and safety. Vigorous research needs to continue to help guarantee that the unmet need for safe and effective contraception is satisfied in future generations.