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Estrogen Metabolism & Breast Cancer Risk

Posted by Lena Edwards MD on

 

Protect Your Breasts with DIM

There is SO much more to the breast cancer story than we are told by our doctors! It’s not as simple as hormone replacement therapy equals breast cancer!

Did you know that a major factor dictating the health of you breast tissue is NOT the absolute amount of estrogen in your body, but the way in which your body metabolizes your estrogen?

Let me break this down as simply as possible.

Basic Overview of Estrogen Metabolism

Your body makes three kinds of estrogen: Estradiol (E2), Estrone (E1), and Estriol (E3). E2 is the most potent form of estrogen followed by E1 (1/12th as potent), and E3 (1/80th as potent).

Once E2 has completed its actions on cells and tissues, it is sent to the liver where it is processed before it can be eliminated from the body. The way E2 is processed is a deal maker (or breaker) when it comes to overall health and breast cancer prevention.

Here is a basic schematic outlining how E2 is processed. It is primarily converted into E1 which is then converted into three metabolites: (1) 2-Hydroxymetabolites (2-OHM), (2) 4- Hydroxymetabolites (4-OHM), and (3) 16-Hydroxymetabolites (16-OHM).

 

 

 

 

Why Metabolites Matter

Some of the metabolites of estrogen can stimulate the growth of breast tissue and contribute to the development of breast cancer. Here’s an overview of how estrogen metabolism influences breast cancer risk:

Estrogen Metabolism Pathways Explained:

1. 2-Hydroxylation Pathway (Good): This pathway converts estrogen into metabolites that are very weak estrogens and so less carcinogenic. This pathway is protective against breast cancer.
2. 16α-Hydroxylation Pathway (Bad): The metabolites of this pathway have strong estrogenic activity which promote the growth and proliferation of breast cells. Increased levels of 16- OHM are associated with a higher risk of breast cancer.
3. 4-Hydroxylation Pathway (Bad): 4-OHM of this pathway lead to genetic mutations leading to an increased risk of breast cancer.

Factors Influencing Estrogen Metabolism

There are a boat load of factors that can affect the way your body is processing your estrogen.

Another very important disruptor of healthy estrogen metabolism is improperly dosed conventional hormone replacement therapy (HRT). Any type of estrogen in pill form (especially Premarin), Progestins (like Provera), and the combination of these two (like Prempro) have been associated with an increased risk of breast cancer because of their negative effects on estrogen metabolism. Please note that progesterone is not the same as progestin!

 

 

How DIM Reduces Breast Cancer Risk

Diindolylmethane (DIM) is a compound derived from the digestion of indole-3-carbinol, which is found in cruciferous vegetables like broccoli, Brussels sprouts, and cabbage. DIM has been shown to play a role in modulating estrogen metabolism in a way that reduces breast cancer risk.

How DIM Affects Estrogen Metabolism:

 

1. Promotion of Beneficial Estrogen Metabolites:

 

o 2-Hydroxylation Pathway: DIM promotes the conversion of estrogen to 2-OHM.Remember, these are the weaker estrogen metabolites and protective againstbreast cancer.
o Reduction of 16α-Hydroxylation Pathway: DIM reduces the formation of 16-OHM, the a "bad" estrogen metabolites that have stronger estrogenic activity andare linked to an increased risk of breast cancer.

2. Antiestrogenic Effects:

o Competitive Inhibition: DIM acts as a competitive inhibitor of estrogen at thereceptor level, potentially reducing the overall estrogenic stimulation of tissues.This can be beneficial in conditions where estrogen dominance is a concern, such as certain types of breast cancer.
o Modulation of Estrogen Receptors: DIM can influence the activity of estrogenreceptors, particularly the balance between ER-alpha and ER-beta receptors,which can have implications for tissue-specific estrogen responses.
3. Detoxification and Antioxidant Properties:
o Enhancement of Detoxification Pathways: DIM supports the liver’sdetoxification processes, aiding in the breakdown and elimination of excessestrogens and other potentially harmful substances. This detoxification can helpmaintain a healthy balance of estrogen metabolites.
o Antioxidant Activity: DIM has antioxidant properties that help reduce oxidativestress and protect cells from DNA damage, which is crucial in preventing theinitiation and progression of cancer.

DIM plays a significant role in modulating estrogen metabolism, promoting the formation of beneficial estrogen metabolites, and reducing the risk of hormone-related conditions like breast cancer. Its antioxidant and detoxification properties further enhance its potential health benefits.

The recommended dose is 100 mg to 200 mg per day.