Abstract

More than 15 case–control studies and at least four large cohort studies demonstrated a decrease in the risk of endometrial cancer of about 50% for ever use of combined oral contraceptives (COCs). In most of these studies, this protective effect persisted for more than 10–15–20 years after cessation of the COC. An increasing protective effect with longer duration of COC use has been found in most studies. The beneficial effect was independent of the composition of COC, i.e. dosage and type of progestogen, combined with ethinyl estradiol 30–50 μg/day. COCs with higher progestogen potency seem to be somewhat more effective. Nonhormonal uterine devices have also been found to be strongly protective; however, data on oral or injectable progestogen-only preparations (POPs) including the levonorgestrel-releasing intrauterine system (LNG-IUS) are still rare, but also suggest similar protective action. COCs, POPs, as well as LNG-IUS can effectively reduce endometrial hyperplasia but should only be used in exceptional cases in patients with or after endometrial cancer. In contrast to nonhormonal IUS, systemic side effects cannot be excluded with LNG-IUS, but they are certainly rare, as the main effect has decreased the endometrial estrogen response because of the high endometrial tissue levels of LNG.