2hydroxyestrone

2-Hydroxyestrone, also known as 2-OHE1, is a catechol estrogen and a major phase I metabolite of estrone (E1) and estradiol (E2) formed by hydroxylation at the 2-position of the steroid A-ring. This metabolic step is carried out primarily by cytochrome P450 enzymes, including CYP1A1, CYP1A2, and CYP1B1, making it one of the principal routes of estrogen metabolism in humans.

The 2-hydroxylation pathway tends to produce metabolites with weaker estrogenic activity compared with products of other hydroxylation routes such as 16α- or 4-hydroxylation. 2-Hydroxyestrone can be further metabolized by catechol-O-methyltransferase (COMT) to 2-methoxyestrone and then conjugated for excretion via sulfation or glucuronidation.

Biological and clinical significance of 2-hydroxyestrone is the subject of ongoing research. It is often described as less estrogenic and potentially anti-estrogenic in some contexts, though effects can depend on concentration and receptor environment. Additionally, catechol estrogens can be oxidized to reactive quinones under certain conditions, a pathway that has been implicated in DNA damage, though this reactivity is generally lower for 2-hydroxyestrogens than for some other hydroxylation products.

In epidemiology and risk assessment, the ratio of 2-hydroxyestrone to 16α-hydroxyestrone (the 2/16α ratio) has been studied as a biomarker of estrogen metabolism. Findings linking this ratio to cancer risk are inconsistent. 2-Hydroxyestrone is detectable in urine or plasma in free and conjugated forms and can be influenced by age, sex hormone status, diet, smoking, and genetics.