Research focus is shifting toward 4-hydroxyesterone which is thought to have greater estrogenic and genotoxic potential than either 2-hydroxyestrone or 16a-hydroxyestrone. Metabolites of 4-hydroxyestrone may induce DNA damage through redox cycling, which generates reactive oxygen species and form reactive semiquinones and quinones capable of forming adducts with glutathione and purines in DNA. However, studies demonstrate that when DNA is incubated with quinones in the presence of an antioxidant, the formation of the DNA adducts is reduced.

- In patients with a low 2-hydroxylation result, metabolism may be shifted toward this pathway by dietary interventions rich in cruciferous vegetables; flax; soy; rosemary and turmeric; exercise that increases lean body mass and decreases BMI; and supplementation with broccoli derivatives indole-3-carbinol (I3C) or diindolylmethane (DIM), as well as omega-3 fatty acids, and vitamins B6, B12 and folate. 

- Support of antioxidant activity appears to be a reasonable proactive step for reducing risk of hormone-related disease. Several natural compounds have exhibited the ability to minimize DNA adduct formation/damage including, resveratrol, N-acetylcysteine, lipoic acid, and melatonin. Cruciferous and allium vegetables also demonstrate the ability to induce glutathione S-transferases.