Background: Over the last 50 years, there has been intense interest in the type of progestin used in combined oral contraceptives (COC) in an attempt to exploit novel properties and minimize adverse events. At the same time, the dose of synthetic estrogen, ethinylestradiol, in COC pills has been reduced to minimize risks for ischemic stroke, myocardial infarction, and venous thromboembolism. New formulations, including extended-cycle or continuous-use COCs or those that use a natural estrogen, estradiol, may offer improvements over their predecessors.
Methods: A Medline search was performed to encompass studies published since 1990 that pertain to the pharmacology of estrogens and progestins used in COCs, risks and adverse events associated with COCs, and extended or continuous-use COCs.
Results: New progestins structurally related to progesterone and spironolactone may exhibit more selective binding to the progesterone receptor and lack androgenic adverse effects associated with progestins structurally related to testosterone. Recently, COCs containing natural (17β-estradiol) or conjugated estrogen (estradiol valerate) rather than ethinylestradiol have been developed in order to move to a more natural estrogen. Although many of the new progestins incorporated into COCs have not demonstrated the negative effects on lipid metabolism and other adverse events associated with the traditional progestins, the goal of attaining good cycle control has yet to be achieved. Extended-cycle and continuous-use regimens are now available that reduce the frequency of menses, but breakthrough bleeding remains a problem.
Conclusions: Appropriate counseling to raise awareness of the specific characteristics of the different COC options available may optimize adherence and patient acceptability.