What Is Estradiol?
Estradiol is a sex hormone and steroid. Estradiol-17β (E2) is the most active estrogen in the body. It is produced mainly in the ovary, but the brain, fat tissue, immune cells, and bones can also produce estradiol .
In the brain, P-450 aromatase enzymes are responsible for its formation. Estradiol levels are highest at birth, and gradually decline as we age .
When women age, their estradiol levels become lower.
In the blood, estradiol exists in 2 forms. It is either bound to proteins (SHBG or albumin) or is unbound (free). It is difficult to measure or predict free estradiol levels, and thus, most estradiol measurements only measure bound estradiol .
Estradiol levels in healthy people can range from 40 to 2,000 pg/mL. This is due to the differences between children (before puberty), pregnant women, and post-menopausal women .
Estradiol range in women during a menstrual cycle:
Estradiol and other estrogen levels can be measured through blood tests and urine tests .
Estradiol levels can be used for ovarian reserve testing (a fertility test) because this helps check follicular activity. Although it is fast and inexpensive, it is never used alone as a marker for ovarian reserve because many factors can increase estradiol .
Positive Estradiol Effects
1) Female Development & Reproduction
Estradiol is important for female development since it is the main source of estrogen. It drives the development of secondary sex characteristics (breasts, widened hips, etc.) from birth to puberty [7, 8].
It also affects the brain and behavioral differences between males and females .
Estradiol also plays a role in pregnancy. At normal levels, it helps maintain pregnancy. But at high levels, estradiol reduces fertility, and it is used in birth control pills .
2) Male Reproduction
Males also need estradiol for their sexual development and function as it helps with erectile function, sperm formation, and sexual libido. However, its exact roles are still unknown .
When estradiol receptors are stimulated, it can help prevent cell death (apoptosis) in penis tissues .
Still, there must be a perfect balance of estradiol and testosterone in the brain, testes, and penis. Too much estradiol may decrease a person’s sex drive. Also, high estradiol and low testosterone may cause breast development in men .
3) Important for Brain Function
Estradiol plays a role in the creation of connections between nerve cells in the brain; it may inhibit or promote this process depending on the location within the brain. It also influences the physiology of developing nerves in the brain .
Estradiol may be responsible for the differences in brain function between sexes. There are differences in thinking, stress, anxiety, aggression, and movement in males and females .
Estradiol also promotes or prevents cell death (apoptosis) in some parts of the developing brain, which contributes to sex differences. For this reason, large doses of estradiol can also be toxic .
In a study of 31 males and 39 females, during a menstrual cycle, women with higher estradiol levels performed better on memory tasks than the women with low estradiol. The high estradiol group was also more accurate than the males .
A review also showed that post-menopausal women, who have lower estradiol, performed worse on verbal memory and fluency tasks than pre-menopausal women .
However, in another study of 16 healthy women, estradiol levels were not associated with brain function, memory, or learning .
Estradiol helps protect against cortisol’s negative effects on the brain. With lower estradiol levels, post-menopausal women are more susceptible to stress and have worse brain function in response to stress .
4) Helps Maintain Weight
In females, estradiol also plays a role in controlling appetite, energy usage, body weight, and fat distribution .
Estradiol helps control CCK, a hormone that controls satiety and digestion. Various human studies showed that estradiol had a controlling effect on meal size and fullness. Post-menopausal women with lower estrogen levels gained weight, but those who had hormone therapy did not .
Additionally, blood levels of estradiol are important signals that control feelings of fullness (satiety) and the hypothalamic-pituitary-gonadal (HPG) axis, which is involved in eating. In various female rat studies, the lack of estradiol in the blood and a dysfunctional HPG axis can cause the rats to overeat and become obese .
5) Supports Thyroid Function
Estrogen has both direct and indirect effects on thyroid function. There are estrogen receptors in thyroid tissues (ERα and ERβ) .
Thyroid diseases and thyroid cancer are more common in women, suggesting that estrogen plays a role in the start of thyroid diseases.
When estrogen binds to ERα, it promotes thyroid cell formation and growth. In contrast, ERβ suppresses thyroid tumors and causes thyroid cancer cell death. Thus, a perfect balance of estrogen in thyroid cells is needed .
In rats, low estrogen levels caused the thyroid to underperform. Meanwhile, high estrogen levels caused hyperactivity in the thyroid .
6) Supports Bone Development
Estrogen is needed for adequate bone growth and the maintenance of bones and joints .
Post-menopausal women with both early and late forms of osteoporosis have estrogen deficiency. Estrogen deficiency also contributes to the development of osteoporosis in elderly men .
Estrogen prevents the formation of certain bone cells (osteoclasts) that cause the breakdown of bone tissue (resorption). Without estrogen, osteoclasts can decrease bone mass and bone strength .
7) Improves Skin Health
Estrogen plays a big role in skin health. There are many estrogen receptors on the skin. Estrogen is important for skin strength, thickness, and even hair growth .
Estrogen helps with wound healing. A review showed that lower estrogen levels can cause excessive inflammation and prevent proper wound healing .
A review of human and animal studies showed that topical estradiol helped improve skin collagen levels, reduced wrinkling, improved skin moisture, and helped heal wounds and scars .
8) May Improve Heart Health
After menopause, women’s estradiol levels may decrease by around 75 to 90%. It is possible that increased age and low estrogen levels contribute to heart disease. Although there are not many studies available, there is some evidence available that suggests estrogen deficiency increases heart disease risk .
A review showed that women who undergo premature menopause develop heart disease earlier as well. Additionally, women with ovarian failure have a higher rate of heart disease .
Various prospective studies showed a potential protective effect of hormone therapy against heart disease .
However, a single-blinded study of 2,700 women found that estrogen therapy did not reduce heart disease rate .
Additionally, during menopause, women are more likely to develop metabolic syndrome (high blood sugar, high blood pressure, high cholesterol, weight gain). Metabolic syndrome plays a big role in heart disease risk. Estrogen deficiency is thought to contribute to metabolic syndrome, and thus, also contribute to heart disease .
Negative Effects of High Estradiol
1) May Increase Cancer Risk
Estrogen may activate certain cancer-causing genes (BRCA1, BRCA2, etc.), which increases the risk of breast cancer and endometrial cancer. Other genes that are involved in estrogen formation (CYP17, CYP19, and HSD17B1) are also associated with cancer [39, 40, 41].
A study of data collected over 50 years showed that estradiol (E2)-progestogen therapy in post-menopausal women was associated with an increase in breast cancer 3 years after the therapy .
High levels of estradiol in men may also increase the risk of prostate cancer. Although various studies have conflicting results, most conclude that estrogen is associated with a higher risk for prostate cancer due to changes in genes and increases in inflammatory markers (IL-1β, IL-6, iNOS, etc.) .
Estrogen transmission may also play a role in thyroid cancer. Estrogen can help with cancer cell growth, and an increased ratio of estrogen receptor (ERα/ERβ) plays a role in tumor progression .
2) May Increase Stroke Risk
In a 6-year study of 16,000 post-menopausal women, the group of women who took 0.625 mg of estrogen plus progestin daily had a higher risk of stroke than the group who only took a placebo. The women were generally healthy and had no other risk factors, indicating that estrogen is responsible for the increased stroke risk [47, 48].
However, in a review, researchers showed that the increase in stroke risk after hormone therapy was rare. Still, the risk is not negligible, and patients should be careful when taking estrogen therapy .
How to Increase/Decrease Estradiol Levels Naturally
Certain phytoestrogens can mimic some of the effects of estrogen. The following are considered phytoestrogens:
Reducing the level of aromatase enzyme activity, which is an important enzyme for the production of estradiol, can reduce the level of estradiol in the body .
You can reduce aromatase activity by:
- Reducing your body fat 
- Increasing zinc, selenium, and magnesium intake to inhibit aromatase 
- Increasing the intake of foods containing natural aromatase inhibitors, including mushrooms, celery, carrots, spinach, and grapes 
- Reducing alcohol consumption 
- Reducing carbohydrates in your diet, since a high carbohydrate diet can increase estrogen levels 
- Brussels sprouts
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