Optimal Result: 0.7 - 2.6 ng/mg.

Both 16a-OHE1 and 4-OHE1 have been referred to as the “bad” estrogens.

- This estrogen metabolite is a more potent estrogen than the other two (2-OH and 4-OH). If this value is elevated, we may see estrogen dominance. 

- Estrogen is also metabolized through the ’16’ pathway. We need this route however it should be used significantly less than the 2-OH pathway. Phase 1 in the 16-Hydroxyestrone pathway is also hydroxylation. Phase 2 is a reduction phase that produces Estriol which is a weak estrogen.

16α-Hydroxyestrone (16α-OH-E1), or hydroxyestrone, also known as estra-1,3,5(10)-trien-3,16α-diol-17-one, is an endogenous steroidal estrogen and a major metabolite of estrone, as well as an intermediate in the biosynthesis of estriol. It is a potent estrogen similarly to estrone, and it has been suggested that the ratio of 16α-hydroxyestrone to 2-OH-E1, the latter being much less estrogenic in comparison and even antiestrogenic in the presence of more potent estrogens like estradiol, may be involved in the pathophysiology of breast cancer. Conversely, 16α-hydroxyestrone may help to protect against osteoporosis.

Synthetic and Natural Estrogens:

Estrone (E1), estradiol (E2) and estriol (E3) are the three estrogens. Synthetic estrogen (premarin) is made up of E1 and E2 estrogen. E1 is the main estrogen that the body makes post menopausally, and most researchers believe that high E1 levels increase the risk of breast cancer. 

Estrogen Metabolism:

The metabolism of estrogen in women changes after menopause. The body metabolizes estrogen into two major pathways and one minor. The two major are 2 and 16-hydroxyeone (2-OH and 16 OH, respectively). The minor pathway is 4-hydroxyestrone (4-OH). 2-OH is the good metabolite. 2-OH does not stimulate cell growth and it blocks the action of stronger estrogens that may be carcinogenic. 

16-OH has a significantly stronger estrogenic activity, and studies show that it may increase the risk of breast cancer. 

4-OH is also not desirable as it may directly damage DNA and cause mutations, thus it is thought to promote cancer development. Premarin breaks down exclusively into 4-hydroxyestrogen.

What does it mean if your 16-OH-E1 result is too low?

Low levels of the “bad estrogen” are typically considered beneficial.

16-OH-E1 is the immediate precursor to the weak estrogen, estriol (E3). Please also note that 16-OH-E1 is important for maintaining bone mineral density. Excessive reduction of 16-OH-E1 may reduce bone formation and increase oxidant stress.

If 16-OH-E1 is low and 2-OH-E1 is low, then total estrogen production may be low. Address underlying causes of low hormone production, as needed.

 

What does it mean if your 16-OH-E1 result is too high?

- Higher levels of the 16 pathway are associated with breast cancer, obesity, hypothyroidism, pesticide toxicity (organochlorines), high Omega-6 fatty acids, and inflammatory cytokines.

- 16-OH-E1 has been shown to encourage tumor development

Lowering levels of 16aOH-E1 have been achieved via indole-3-carbinol or one of its metabolites, di-indol methane (DIM). Soy and flax meal have also been shown to lower 16aOH-E1 levels.

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