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Gene Talk

Estradiol Plasma Levels And Breast Cancer Risk

Estradiol Plasma Levels And Breast Cancer Risk

Estradiol (E2) is a type of estrogen steroid hormone. It is one of the female sex hormones and is responsible for managing the reproductive cycle. It also plays a major role in the reproductive health of a woman.

Both men and women have natural estradiol hormones in the body. A woman’s body produces more estradiol than a man’s.

The Role of Estradiol In Reproductive Life

- Helps in female sexual development — characterized by signs like the growth of breasts and the widening of the hips.
- Helps the vulva and vagina mature
- Plays a role in controlling growth spurt during puberty
- Acts as a growth hormone for the tissues and linings of the female reproductive system

What Happens When Estradiol Levels Are Low?

- Increased risk of bone fractures and osteoporosis (low bone density)
- Delayed puberty in younger girls
- Mood swings
- Signs of skin aging including the appearance of wrinkles, fine lines, and loss of skin elasticity

What Happens When Estradiol Levels Are High?

- Increased risk of Ischemic Arterial Diseases in postmenopausal women
- Increased risk of weight gain
- Abnormalities in the menstrual cycle
- Lowered sex drive
- Increased risk of breast and uterine cancer

Estradiol Levels and Breast Cancer Risk

According to the American Cancer Society, the incidence rate of breast cancer has been increasing by 0.5% every year. Breast cancer is the second leading cause of cancer deaths in women in the United States.

Excess estradiol in the body interacts with two Estrogen Receptors (ERs) — ERα and ERβ. Estrogen receptors are proteins that get activated on exposure to estrogen. These ERs are responsible for controlling a variety of genes and their functionalities.

The ERα interacts directly with DNA repair proteins with varying impacts on DNA repair mechanisms. In some cases, it can result in abnormal cell production and multiplication, leading to breast cancer.

A 2002 study analyzed the effects of serum E2 levels and the risk of breast cancer. 7290 postmenopausal women under the age of 80 were included in the study. The study records that women with estradiol levels higher than 10 pmol/L had a 6.8 fold higher risk for breast cancer.

According to a 2001 study, postmenopausal women with higher estradiol levels (>12 pmol/L) had a 2.07 fold higher risk for invasive breast cancer.

Another study explored how estrogen metabolism influences breast cancer risk. 1298 postmenopausal women with cases of breast cancer and 1524 matched controls were considered for the study. The study reported that total estrogen levels were positively and strongly associated with breast cancer risk.

Genetic Factors Influencing Estradiol Plasma Levels And Breast Cancer Risk

The CYP19A1 Gene

The CYP19A1 gene produces an enzyme called aromatase. Aromatase helps convert androgens (hormones associated with male traits) to different forms of female hormones (estrogen).

This enzyme is very important in the production and maintenance of female reproductive hormones. This enzyme is also needed for the last step of estrogen production in the body (biosynthesis).

Certain types of CYP19A1 gene can lead to excess production of estradiol, leading to an increased risk for breast cancer.

Increased aromatase levels lead to a lower survival rate in people with Estrogen Receptor-Positive Breast Cancer.

Family History

Women who have increased estradiol levels in the body and a family history of breast cancer (first or second-degree relatives with a past or present cancer diagnosis) are at higher risk.

Non-Genetic Factors Influencing Estradiol Plasma Levels And Breast Cancer Risk

Gender: 99 out of 100 breast cancer cases occur in women, making the female sex a risk factor for breast cancer.

Hormone Replacement Therapy: Hormone Replacement Therapy (HRT) is recommended for women during their menopausal period to help manage the symptoms better. There are two common types of HRT procedures recommended:

- Estrogen-only HRT
- Combination HRT (estrogen+progesterone)

Combination HRT increases the levels of estradiol in the body. This can increase the risk of breast cancer by up to 75%.

Estrogen-only HRT also increases estradiol levels, but the effects are seen only after 10 years.

According to a 2005 study, Hormone Replacement Therapy (HRT) remains the most important risk factor for ER+ breast cancer.

Reproductive cycle: Girls who get their periods before 12 and women who don’t experience menopause before 55 are more exposed to estrogen. This increases estradiol levels in the body and can increase the risk for breast cancer.

Breastfeeding duration: Women who breastfeed have higher levels of prolactin. Higher prolactin levels lead to lower estradiol levels. Hence, women who breastfeed for a longer duration may be protected against breast cancer.

Gut health: The human Gastrointestinal Tract (GI tract) contains billions of bacteria, viruses, and other microorganisms that keep the body healthy.

Estradiol is produced in the adrenal glands, ovaries, and adipose tissues. It circulates through the bloodstream and is converted into usable forms in the liver. The remaining estradiol is sent out to the bile and the urinary tract. Certain bacterial species can pull out this estradiol from the bile and send it back to circulation. This leads to increased estradiol levels and an increased risk of breast cancer.

Obesity: According to a 2010 study, in postmenopausal women, obesity was associated with increased levels of estradiol. Obese women had higher levels of estradiol when compared to non-obese women. This increases their risk for breast cancer too.

Recommendations to lower Estradiol Plasma Levels

Genetic Testing

Genetic testing can help assess your breast cancer risk by analyzing your BRCA genes. It also helps analyze other risk factors like estrogen exposure. You can talk to a genetic counselor to get more information on this.

Be Aware of Exposure to Chemicals

Certain chemicals used in making everyday products can cause problems in the endocrine system. These are called Endocrine Disrupting Chemicals (EDCs).

Some of these chemicals are:

- bisphenol A (BPA)
- bisphenol B
- bisphenols F
- bisphenols S
- tetrabromobisphenol A
- dichlorodiphenyltrichloroethane (DDT)
- dichlorodiphenyldichloroethylene (DDE)
- dichlorodiphenyldichloroethane (DDD)

Most plastics used at home have one or more of these chemicals in them. A study reported that younger people who have a higher exposure to BPA and have early puberty show higher estradiol levels in the body.

In another study, female rats that were exposed to higher levels of Endocrine Disrupting Chemicals (EDCs) showed increased levels of estradiol.

Switching over to more natural crockeries, tableware, and cookware can help bring down the risk of increased estradiol levels.

Maintain A Healthy Weight

Maintaining a healthy weight can help reduce estradiol fluctuation in the body and decrease the risk of breast cancer.

Regular Screening For Breast Cancer During Menopause

Women’s natural estradiol levels fluctuate extremely during menopause. Perimenopausal women (women in menopause) may have up to two times the normal estradiol levels.

During this period, it will help if you are regularly screened for breast cancer. This will help with early diagnosis and a better prognosis.

Summary

- Estradiol is a major type of estrogen steroid hormone responsible for maintaining the female reproductive system. While both men and women produce estradiol in their bodies, the levels are higher in women than in men.
- Higher levels of estradiol in the body are associated with an increased risk of breast cancer and uterine cancer.
- The CYP19A1 gene produces an enzyme called aromatase. This enzyme converts androgens to estrogens. Certain changes in this gene can increase the risk for breast cancer.
- Some women may also have a family history of breast cancer and increased estradiol levels. The combination of both further increases the risk of breast cancer.
- Women who opt for Hormone Replacement Therapy have increased estradiol levels in the body. This increases the risk of breast cancer.
- Girls who reach puberty early and women with delayed menopause are more exposed to estradiol in their lifetimes and have a higher risk for breast cancer.
- Certain bacteria in the gut may increase the levels of circulating estradiol in the body. This also increases the risk of breast cancer.
- Genetic testing can help assess your risk for breast cancer. It analyzes your BRCA genes and other factors that contribute to breast cancer risk.
- Losing weight and regular breast cancer screening during menopause can help you manage breast cancer risk more effectively.
- Staying away from chemicals like BPA and DDTs brings down estradiol levels in the body.

References

- https://www.medicalnewstoday.com/articles/323178
- https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/estradiol
- https://en.wikipedia.org/wiki/Estradiol#Biological_function
- https://www.medicalnewstoday.com/articles/316779#outlook
- https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-018-1073-0
- https://pubmed.ncbi.nlm.nih.gov/20623183/
- https://www.cancer.gov/about-cancer/causes-prevention/risk/hormoneshttps://jamanetwork.com/journals/jamasurgery/fullarticle/508262https://www.frontiersin.org/articles/10.3389/fonc.2016.00267/full

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