Healthy Phase II metabolism methylates 2-hydroxy (2-OH) estrogens to the more cancer-protective 2-methoxy (2-MeO) forms, and neutralizes the potentially carcinogenic 4-OH estrogens to their 4-MeO forms.
4-Methoxyestradiol (4-ME2) is an endogenous, naturally occurring methoxylated catechol estrogen and metabolite of estradiol that is formed by catechol O-methyltransferase via the intermediate 4-hydroxyestradiol. It has estrogenic activity similarly to estrone and 4-hydroxyestrone. Estradiol is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips, and a female-associated pattern of fat distribution and is important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus, and vagina during puberty, adulthood, and pregnancy.
It also has important effects in many other tissues including bone, fat, skin, liver, and the brain. Though estradiol levels in males are much lower compared to those in females, estradiol has important roles in males as well. Levels of estradiol in premenopausal women are highly variable throughout the menstrual cycle and reference ranges widely vary from source to source.
Low levels can indicate inadequate methylation and therefore may be associated with an increased breast cancer risk.
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