The high doses of EE that were used in early COCs were associated with a significantly increased risk of endometrial cancer in certain preparations, for instance those containing the progestogen dimethisterone. Unopposed estrogens like EE have carcinogenic effects in the endometrium and progestogens protect against these effects, but dimethisterone is a relatively weak progestogen and was unable to adequately antagonize the endometrial carcinogenic effects of EE, in turn resulting in the increased risk of endometrial cancer. COCs containing dimethisterone have since been discontinued (with more potent progestogens used instead) and doses of EE in COCs in general have been dramatically reduced, abrogating the risk. In turn, most studies of modern COCs have found a decreased risk of endometrial cancer.