Estrogen is a female sex hormone that helps in the development and maintenance of the female reproductive system. There are four types of estrogens produced in the body.

• Estrone (E1)
• Estradiol (E2)
• Estriol (E3)
• Estetrol (E4) - produced only during pregnancy

This steroid hormone is produced in the ovaries, placenta, and the corpus luteum (a structure in the ovary that develops every month after the ovum is released and disappears after a few days) in premenopausal women. The liver, heart, and brain also produce minimal amounts of estrogen. 

Though estrogen is most important for women, men also need it in minimal quantities to produce sperm cells and maintain sexual drive/desire.  

Biological Functions Of Estrogen

Development Of Female Secondary Sexual Characteristics

Estrogen is essential for the growth of female secondary sexual characteristics, including:

• Formation of breasts
• Widening of hips
• Growth of body hair

Regulation And Maintenance Of Menstrual Cycle

Estradiol (E2) helps in the production of the Follicular Stimulating Hormone (FSH) and the Luteinizing Hormone (LH). Both these hormones are necessary for regular ovulation and the menstrual cycle.

Growth And Maturation Of Reproductive Organs

The female reproductive organs have to mature healthily for a successful pregnancy. Estrogen helps in the following ways.

• Encourages endometrial growth
• Thickens vaginal wall
• Increases uterine growth
• Increases lubrication in the vagina

Development Of Mammary Glands

Mammary glands help in the production of milk after delivery. Lack of estrogen leads to immature mammary glands and problems in breastfeeding. 

Bone Development And Maintenance

Estrogen helps in skeletal growth. It causes changes in the physique of girls going through puberty. Estrogen also helps maintain bone mineral density. Lack of estrogen increases the risk of osteoporosis. 

Brain Behavior 

Estrogen is important for the growth and functioning of axons and dendrites in the brain. Axons are nerve fibers, and dendrites are portions of nerve cells. Some studies also link estrogen to normal cognitive development, the ability to learn, remember, solve problems, think, and reason. 

Heart Health

Estrogen reduces LDL cholesterol levels in the body and hence helps protect heart health. Estrogen also helps in maintaining blood vessel structure. 

Estrogen Detoxification/Metabolism 

While the right amounts of estrogen is beneficial for the body, excess levels can cause harm. Excess estrogen is eliminated from the body in the three stages of detoxification. This hormone goes through different transformations in each of the stages.

Phase 1 Detoxification of Estrogen

The Cytochrome P450 (CYP) enzymes are responsible for the first stage of estrogen transformation. The CYP enzymes are substances that play a role in the detoxification and clearance of drugs, hormones, and other substances from the body.

Three main CYP enzymes act on estrogen. They are:

• CYP1A1
• CYP1B1
• CYP3A4

In phase 1, a hydroxyl group (-OH) is attached to the estrogen hormones, and as a result, the following intermediates are produced.

• CYP1A1 converts estrogen to 2-hydroxyestrone and 2- hydroxyestradiol
• CYP1B1 converts estrogen to 4- hydroxyestrone and 4-hydroxyestradiol
• CYP3A4 converts estrogen to 6α- hydroxyestrone

These intermediates are called metabolites. These metabolites are very reactive and need to be quickly cleared by phase 2 and phase 3 detoxification. When produced in excess, these metabolites react with the DNA and lead to an increased risk of cancers. 

Phase 2 Detoxification of Estrogen

In Phase 2 detoxification, these hydroxyl metabolites become less reactive and more stable with the addition of a methyl group. The Catechol-O- MethylTransferase (COMT) enzyme is responsible for the methyl group addition.

The substances produced as a result are:

• 2-methoxyestrone
• 4-methoxyestrone
• 2-methoxyestradiol
• 4-methoxyestradiol

Unlike the earlier metabolites, these are safer and neither react with the DNA nor lead to abnormal DNA transformations. 

Apart from methylation, estrogen also goes through sulphation using the sulfotransferase (SULT) enzymes. The SULTs attach estrogen with sulfate molecules. Conjugation is the process of making the hormone more water-soluble to make it easy for excretion. Estrogen sulphation creates estradiol, and this is sent back to circulation in the body. 

Estrogen also goes through a third process called glucuronidation in phase 2. In this process, estrogen conjugates with glucuronic acid using the UDP-glucuronosyltransferase (UGT) enzyme. This makes it easier for estrogen to be eliminated from the body.

However, another enzyme called β-glucuronidase that is found in the breast glands and the gut can reconvert the conjugated estrogen back into free estrogens. This reconversion leads to abnormally high estrogen levels in the body. 

Phase 3 Detoxification of Estrogen

Phase 3 is the final stage of detoxification. Here, estrogen metabolites leave the body through urine or bile. The antiporter proteins help in phase 3. These are also called exchanger proteins. These proteins carry substances in and out of the cells and help eliminate the final estrogen metabolites.

What Causes Changes In Estrogen Metabolism?

The β-glucuronidase enzyme found in the breast cells and gut can create problems in the functioning of the antiporter proteins. As a result, it leads to excess estrogen circulation. 

Changes in genes like CYP1A1, CYP1B1, CYP3A4, COMT, SULTs, and UGTs can lead to estrogen production problems and increase or decrease the hormone levels in the body. 

Effects Of Low And High Levels Of Estrogen

Low levels of estrogen may result in:

• Vaginal dryness due to lack of lubrication
• Irregular periods
• Breast tenderness
• Mental health conditions like depression, mood swings, and trouble concentrating
• Hot flashes
• Night sweats
• Fatigue and general tiredness
• Increased risk for osteoporosis
• Increased risk for heart diseases

High levels of estrogen may result in: 

• Bloating
• Breast tenderness
• Lack of sexual drive 
• Mood swings
• Anxiety and depression
• Abnormal weight gain
• Sudden and unexplained headaches
• Irregular periods
• Hyperpigmentation of the skin
• Abnormal uterine bleeding

Estrogen Metabolism And Breast Cancer

According to the National Cancer Institute, there will be 281,550 new cases of breast cancer diagnosed in the United States in 2021. Latest studies report that estrogen levels in the body may play a role in breast cancer.

While age and genetics play the most important role in causing breast cancer, lifetime exposure to estrogen is also an important cause. 

The CYP enzymes convert estrone to 2-hydroxyestrone, 4-hydroxyestrone, 16-hydroxyestrone, or estriol. They also convert estradiol to 2-hydroxy estradiol and 4-hydroxy estradiol. This conversion process releases free radicals that increase the risk of all types of cancers, including breast cancer. 

Estrogen Receptor α (ERα) is a group of proteins that estrogen activates. Once activated, ERα attaches itself to the DNA and controls the activity of different genes.

According to studies, certain changes in the estrogen hormone can lead to changes in the ERα too. The ERα causes errors in DNA replication and leads to multiple, abnormal divisions of cells. This leads to the formation of tumors.

Breast cancer that develops because of estrogen receptors is called estrogen receptor-positive breast cancer (ER-positive breast cancer). This accounts for 80% of all breast cancers. 

Recommendations To Boost Estrogen Metabolism

Estrogen Levels Test 

An estrogen levels test will measure the estrogen levels in the blood and urine. This test can individually measure E1, E2, and E3 levels. Getting the test will tell you if you are at a higher risk for estrogen-associated health conditions. 

Genetic Testing

Specific genetic changes can affect the levels of estrogen levels in the body. Some people will have naturally higher estrogen levels that could increase the risk of breast and other types of cancers. Genetic testing will help confirm if the person is at higher risk for abnormal estrogen metabolism. 

Does A Plant-based Diet Benefit Estrogen Metabolism?

A 2019 meta-study analyzed the relationship between diet and risk of breast cancer. It included results from 32 articles and reported the following:

• People who followed a Western dietary pattern (a diet rich in sugar, red meat, refined grains, and processed foods) had an 18% higher risk of developing Estrogen Receptor (ER+) breast cancer.
• People who followed a Prudent dietary pattern (a diet rich in fresh fruits, vegetables, salads, and fish) had a 20% reduced risk of developing ER+ breast cancer. 

Dietary phytoestrogens are types of foods that cause estrogen-like effects in the body. Plant-based foods are the primary sources of dietary phytoestrogens. Studies report that these phytoestrogens help balance the endocrine system and bring down the risk of estrogen receptor-positive breast cancer. 

Other studies mention that dietary phytoestrogens affect the 2-hydroxy estrone to 16α-hydroxy estrone ratio. This regulates estrogen metabolism and reduces the risk of breast cancer.  

A small study picked up 272 participants, including 37 semi-vegetarians (women who consumed less than 30 g of meat a day) and 235 non-vegetarians (whose primary diet included red meat every day). This study reported that serum estrone and estradiol levels in semi-vegetarians were lower when compared to non-vegetarians. 

Another study divided 115 women into two groups - control and intervention. Women in the intervention group were put on a Mediterranean diet (including fish, fresh fruits, vegetables, greens, and dairy). The control group followed a regular western diet style. At the end of 6 months, women in the intervention group had up to 40% lower estrogen levels than the control group.

Foods rich in fiber help with better estrogen metabolism and bring down excessive estrogen levels in the body. Fiber can flush out cholesterol deposits (cholesterol leads to estrogen production). Some plant-based fiber foods that can aid estrogen metabolism are:

• Lentils
• Apples
• Oats
• Barley
• Green peas
• Artichokes
• Avocados
• Chia seeds
• Pears
• Broccoli
• Raspberries

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Summary

1. Estrogen is a type of female sex hormone that helps in the growth and maintenance of the female reproductive system. 
2. Estrogen plays a role in the maintenance of bone health, heart health, and brain health.
3. The CYP enzymes, COMT enzyme, SULT enzymes, and UGT enzymes help in estrogen detoxification.
4. The activity of the β-glucuronidase enzyme found in the breasts and gut can reconvert back the estrogen intermediates to active estrogen and increase the hormone levels in the body.
5. Certain changes in the CYP1A1, CYP1B1, CYP3A4, COMT, SULT, and UGT genes can increase or decrease estrogen metabolism.
6. Both increased and decreased levels of estrogen can cause various side effects in the body. An increase in estrogen levels can lead to tumors.
7. Getting an estrogen levels test and genetic testing done can tell if a person is at a higher risk for estrogen-induced health conditions.
8. A plant-based diet plan may help naturally bring down hormone levels and improve estrogen metabolism.