Aside from sulfate conjugation, EE is mainly metabolized by hydroxylation into catechol estrogens. This is mainly by 2-hydroxylation into 2-hydroxy-EE, which is catalyzed primarily by CYP3A4. Hydroxylation of EE at the C4, C6α, and C16β positions into 4-, 6α-, and 16β-hydroxy-EE has also been reported, but appears to contribute to its metabolism to only a small extent. 2- and 4-methoxy-EE are also formed via transformation by catechol O-methyltransferase of 2- and 4-hydroxy-EE. Unlike the case of estradiol, 16α-hydroxylation does not occur with EE, owing to steric hindrance by its ethynyl group at C17α. The ethynylation of EE is largely irreversible, and so EE is not metabolized into estradiol, unlike estradiol esters. A review found that the range of the reported elimination half-life of EE in the literature was 13.1 to 27.0 hours. Another review reported an elimination half-life of EE of 10 to 20 hours. However, the elimination half-life of EE has also been reported by other sources to be as short as 7 hours and as long as 36 hours.