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Estrogen - friend or foe?

Estrogen - friend or foe?
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With breast cancer awareness month fast approaching in SA, it's important that we highlight how you can take charge to prevent one of the highest occurring breast cancers - estrogen-positive breast cancer. 

While you may be desensitized to all the "pinkwashing", the truth is that breast cancer is a really BIG health issue that every woman (and man) could face either personally or together with someone close to them.

The two aspects of this disease that really stand out is that 1) we have seen 2 million new cases of breast cancer worldwide in 2018 and 2) about 85% of breast cancers occur in women who have no family history of breast cancer. These occur due to genetic mutations that happen as a result of the "ageing process" and "life in general". Not very comforting if you are facing a breast cancer diagnosis!

Not all breast cancers are the same

A good place to start is to make sure that you are aware of the different types of cancer and their etiologies. The biggest culprit is the 80% estrogen-receptor positive cancer, and this is the type of breast cancer that we can try to prevent. 

  1. Hormone receptor-positive breast cancer. About 80% of all breast cancers are “ER-positive.” That means the cancer cells grow in response to the hormone estrogen. About 65% of these are also “PR-positive.” They grow in response to another hormone, progesterone.
  2. HER2 positive breast cancer. In about 20% of breast cancers, the cells make too much of a protein known as HER2. These cancers tend to be aggressive and fast-growing.
  3. Triple-negative breast cancer. Some breast cancers - between 10% and 20% - are known as “triple negative” because they don’t have estrogen and progesterone receptors and don’t overexpress the HER2 protein. Many breast cancers associated with the gene BRCA1 are triple negative. 

What are we missing?

We believe that it starts with understanding the hormone cascade together with testing how it is working in YOUR body.

In my own personal case, even though I did biology in high school and went onto study a paramedical degree with neurology as a major. However, not once did I learn about the hormone cascade in humans. It was only AFTER I was diagnosed with an estrogen-positive ovarian cancer that I looked a little deeper and stumbled across this info at 38! I should have known about this from 12 years of age. 

Once you understand the intricate biochemistry of your hormones, they seem actually magical! And powerful too. And that's why upsetting this fine balance leads to all sorts of problems in men and women. The truth is that many of us are making daily choices that affect our endocrine system, without knowing the impact.

 

The hormone cascade

This diagram from VITAGEN-X  provides you with a great graphic to see how the hormone cascade works together with the key genes involved in estrogen detox. As you will see it all starts with cholesterol, which is sometimes referred to as the "father of all hormones" because it helps to make your sex hormones estrogen, progesterone and testosterone. 

Estrogen is one of two major female steroid sex hormones, the other being progesterone. The main source of estrogen in females prior to menopause is the ovaries, after which the main source becomes the adrenal glands and fat tissue. Estrogen is also produced by the placenta during pregnancy. Estrogen levels fluctuate throughout life, naturally increasing during puberty and pregnancy, and falling after menopause. During the menstrual cycle, estrogen levels peak during ovulation dropping off if pregnancy doesn’t occur. This is truely amazing!

The main roles of estrogen in the body are to increase the growth and production of cells, the development and regulation of the female reproductive system and secondary sex characteristics - breasts, pubic hair etc. Estrogen is also involved in maintaining bone density, plays a role in blood clotting and affects skin, hair, mucous membranes, and the pelvic muscles.

The body produces 3 different types of estrogen:

  • E1 - Estrone: medium strength, predominant after menopause (adrenal glands)
  • E2 - Estradiol: strongest form, predominant during childbearing age (ovaries & adrenal glands)
  • E3 - Estriol: weakest form, predominant during pregnancy (placenta & liver) 

Estrogen production

E1 and E2 are produced directly from the androgens androstenedione and testosterone respectively. E3 is produced from E2 according to the body's needs. Although androgens are considered male hormones, they play an important part in female physiology since all estrogens are made from androgens. In every tissue where estrogen is produced, it is made from an androgen.

Phase 1 estogen detox

The CYP17A1 enzyme initiates the first step in estrogen production by converting pregnenolone and progesterone into estrogen precursors, including DHEA. The CYP19A1 enzyme is responsible for controlling the rate at which androstenedione and testosterone are converted to estrogen.

Once produced, circulating estrogen is converted via phase I detoxification enzymes:

CYP1A1: produces 2OH estrogen which is ‘weak’ in action and thought to be neutral or even beneficial to the body. This is the most favourable pathway in terms of estrogen metabolism.

CYP1B1: produces 4OH estrogen and generates harmful free radicals in the process. 4OH estrogen has stronger oestrogenic properties than 2OH estrogen and has been associated with undesirable estrogen-linked conditions and to DNA damage. As a result, this is the least favourable pathway of estrogen metabolism.

CYP3A4: produces 16OH estrogen, thought to be stronger than 2OH and potentially harmful, although further research needs to be done. As a result, this is thought to be a less favourable pathway. 

Knowing which phase I pathway/s your body favours is useful since it gives a clue as to which forms of estrogen might be dominant in circulation and the diet and lifestyle measures you should take care to implement or avoid in order to maintain a healthy balance. This is truly empowering. 

Phase 2 estrogen detox 

Once produced, estrogen moves through the blood and exerts its influence in the body by binding to estrogen receptors (ERs). ERs are important since they are also known to bind to DNA and control gene expression.

There are two types of estrogen receptors encoded by two separate genes:

ER alpha (ESR1) - found in the highest concentration in the endometrium, ovaries, and hypothalamus (in the brain). ESR1 increases the action of the attached estrogen

ER beta (ESR2) - found in highest concentration in the ovaries, kidneys, brain, bone, heart, lungs, intestinal mucosa and endothelial cells. ESR2 weakens the action of the attached estrogen.

After phase I conversion, estrogen metabolites pass through phase II detoxification where they are neutralized and prepared for excretion via urine and bile.

The 4 main estrogen detoxification enzymes are:

COMT (Methylation): the COMT enzyme turns 2OH and 4OH into the neutral compounds, 2-meOH, and 4-meOH respectively via a process called methylation. Methylation is a major mechanism for preventing the potentially harmful effects of estrogen in the body.

GSTs (Glutathione Transferases): the GSTs are vital phase II detoxification enzymes responsible for providing protection against toxins by neutralising free radicals in the body with the help of the powerful antioxidant, glutathione.

SULT (Sulphation): estrogen metabolites are also deactivated via sulphotransferase enzymes

UGT (Glucuronidation): the UGT enzymes render estrogen more water-soluble and ready for excretion via the bile to the small intestine

Knowing which of your phase II pathways might be sluggish or in need of extra support is important to prevent your exposure to the toxic estrogen metabolites that have been linked to estrogen-positive breast cancer.

What is the DUTCH test?

The DUTCH test enables you to measure and track which pathway your body is using to metabolise estrogen.

You may suffer from hormonal imbalances. Whether it is menopause, weight gain, fatigue, low libido, premenstrual symptoms (PMS), mood swings, or depression, these symptoms can lead to more serious problems if misdiagnosed.

Identifying the root cause of chronic health issues is certainly correctable, but only if properly identified. The DUTCH test was created to provide insight into many of these concerns, working to deliver the most complete assessment of sex and adrenal hormones along with their metabolites, in one easy-to-do test.

Who should do it?

Everyone from the age of 18! As you enter into your 20s, you'll be making more choices that could really impact on your estrogen detox genes and biochemistry. These include going on contraception, increased toxicity from drinking and partying, late nights, fast foods and increased stress. All these things put pressure on your estrogen pathways. Doing the DUTCH test now will provide excellent insight into your unique body and empower you to make these decisions with knowledge.

You can order THE DUTCH TEST online here:

 

 

Genomics & Functional Medicine - putting it all together 

It's really useful to combine your estrogen genes with a real-time metabolites test to get a complete, personalised picture of your relationship with estrogen.

To find out your unique genetic variations for the key genes mentioned above, you can order the VitaFEM DNA test online here:

 

 

 

 

 

Once you have a picture of your estrogen genes together with how you are metabolising estrogen in real-time, then you will be empowered to make better nutrition, environment and lifestyle choices to ensure that you sending your estrogen down the right path! Our integrated, Functional Medicine base ESTROGEN SHOP details the which nutrients you can add in for each of the phases in estrogen detox together with how to make swap out toxic products that have an estrogen-type effect in your body. 

In essence, we now have access to advanced functional lab tests that can test for biochemical imbalances in your hormone metabolism way before the manifestation of a disease! This is truly empowering and preventative. It is still important to go for your annual pap smear and mammogram but in many cases, the disease has already manifested. Now you can couple these traditional screening methods with more advanced tests that enabled us to go more upstream, right to your biochemistry and DNA.

 Margie 

References

The World Cancer Research Fund

 

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