An Integrative Medicine Approach to Estradiol Imbalance

Estrogen imbalances are common among women. Estrogen can be found in three primary forms: Estrone, Estradiol, and Estriol - all important and each necessary, playing unique roles within the female body.

This article will focus on estradiol, one of the most important female hormones, as it affects the reproductive system and numerous other body systems. Estradiol levels can be considered high or low, potentially contributing to other hormonal imbalances. We will discuss what estradiol is, how to detect an estradiol imbalance, and how to support balanced levels using an integrative approach.

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What is Estradiol?

Estradiol plays a vital role in the menstrual cycle. The menstrual cycle can be divided into three parts: the follicular phase, ovulation, and the luteal phase. The first day of the follicular phase is the first day of menstruation, and estradiol and progesterone are both low at this time. A brain hormone called follicle-stimulating hormone (FSH) is released at this time, and it stimulates multiple follicles to begin growing within the ovary. One follicle will become dominant between days five and seven, and the rest will dissolve. This dominant follicle begins to produce estradiol and will eventually release an egg. Estradiol acts on the uterine lining, causing it to grow or thicken in preparation for a fertilized egg. Estradiol directly stimulates the release of another pituitary hormone, luteinizing hormone (LH), which initiates the next phase, ovulation.

Ovulation lasts for 16 to 32 hours. As estradiol continues to rise, so does LH. In turn, the surge in LH causes growth of the follicle until it eventually ruptures and releases an egg (ovulation). If fertilization occurs, the egg implants into the uterine lining, and the menstrual cycle stops. If the egg is not fertilized, the cycle resumes, and the luteal phase begins.

The luteal phase lasts 14 days from ovulation. In this phase, the remnants of the ruptured follicle turn into a structure called the corpus luteal (CL). The CL produces the other dominant female hormone, progesterone. Without a fertilized egg, the CL will degrade around ten days after its production. Estradiol is also falling at this time, and the decline of both hormones signals the uterine lining to shed (menstruation). The cycle then begins again.  

Estradiol affects numerous body systems in women. In the liver, estradiol helps to increase HDL, deemed the good cholesterol, while lowering LDL, deemed the bad cholesterol. In the skeletal system, estradiol inhibits the breakdown of bones while increasing the creation of new bones and bone mineral density. In the cardiovascular system, estradiol increases blood flow and supports clot formation. Estradiol supports collagen and elastin formation and hyaluronic acid production in the integument system or the skin. In the brain, estrogen helps to increase memory and mood. Estradiol can exert these functions as it is a signaling hormone. Signaling hormones work with their receptors like keys and locks; estradiol is the key, and the receptor is the lock. Estrogen receptors are located all over the body, explaining the effects discussed above.  

High Estradiol Symptoms

High estradiol symptoms may include:

• Headaches
• Weight gain
• Mood swings
• Heavy periods
• Irregular period
• Fibrocystic breasts
• Fibroids
• Low progesterone: high amounts of estradiol can block progesterone synthesis

Low Estradiol Symptoms

Low estradiol symptoms may include:

• Night sweats
• Hot flashes
• Vaginal atrophy: (dryness in the tissues of the vagina leading to painful intercourse and an increased risk of vaginal infections)
• Cardiovascular symptoms including heart palpitations and dizziness
• Fatigue
• Insomnia
• Irritability
• Changes in hair growth
• Headaches
• Memory issues
• Fatigue
• Weight gain
• Dry hair
• Osteoporosis

What Causes Estradiol to Be High?

Chronically high estradiol levels may contribute to breast, ovarian, adrenal, and uterine cancer, endometriosis, polycystic ovarian syndrome, and insulin resistance. Because of this, it is essential to investigate the cause of high estradiol.

Genetic Reasons

The creation and breakdown of estradiol are controlled by enzymes, which are controlled by genes. In estrogen breakdown or metabolism, three steps must be done for estradiol to get out of the body properly. If any of these, or more than one, are running slowly, this can cause a backup of estrogen in the body. Additionally, the third step of metabolism occurs in the gastrointestinal tract microbiome. The microbiome is a collective group of microbes that play a pivotal role in numerous bodily systems. One group of microbes has been called the estrobolome since their sole purpose is packaging estrogen in the stool, which is step three of estrogen metabolism. If the estrobolome is not functioning properly, it will release an enzyme, beta-glucuronidase, which will cause estrogen to be recycled and reenter the bloodstream.  

Nutrients

Various nutrients are required for the enzymes involved in estrogen metabolism to function correctly. Phase I of estrogen metabolism can result in carcinogenic metabolites. Phytonutrients obtained from cruciferous vegetables (broccoli, cabbage, kale, etc.) may help in lowering the production of these carcinogenic metabolites and favor the production of beneficial metabolites. Phase II of estrogen metabolism involves a biochemical pathway called methylation. Methylation requires numerous nutrients, including vitamin b12, folate, magnesium, and more.  

Environmental Exposures

Our environment and many products we use daily contain chemicals that can affect our hormones. Specific chemicals, referred to as estrogen-like endocrine disrupting chemicals (EEDC) or xenoestrogens, can act like estrogen and activate the estrogen receptor. Other chemicals influence and inhibit the proper metabolism of estrogens. Additionally, pesticides used in agriculture may also affect estrogen levels.

What Causes Estradiol to Be Low?

Chronically low estradiol has been associated with osteoporosis and heart disease. Common causes of low estradiol include:

Menopause Transition

Commonly referred to as perimenopause, the menopause transition is the primary cause of low estradiol. For many women, perimenopause comes with periods of high and low estrogen due to dysfunctional follicle development. Women can have multiple dominant follicles, leading to increased estrogen, and then can go months without any dominant follicles, leading to low estrogen.

Menopause begins twelve months after the last period. This event marks the permanent end of reproduction, as the ovaries are depleted of eggs, thus stopping hormone production. The adrenal glands will make small amounts of hormones, but nowhere near the level that the ovaries once produced.

Hypothyroidism

Hypothyroidism occurs when the thyroid gland does not produce adequate amounts of hormones. Thyroid hormones can influence various menstrual cycle phases, including follicular development and ovulation. Because of this, we typically see menstrual irregularities with hypothyroidism and, thus, low estradiol.  

Stress

Stress, whether mental, physical, or emotional, can affect hormone production. Regarding estradiol, high-stress levels have been shown to lower estradiol levels and inhibit peak estradiol levels.

Other Causes

Other causes of low estradiol include eating disorders, premature menopause, autoimmune conditions, genetic conditions, damage to the ovaries, damage to the pituitary gland, and excessive stress.

Functional Medicine Labs to Test for Root Cause of Estradiol Imbalance

DUTCH Test

The DUTCH test, by Precision Analytics, is a dried urine test that assesses hormone metabolites. This test gives excellent insight into the metabolism of hormones, including estradiol.  

This test also shows cortisol levels, our primary stress hormone, and how it is metabolized. Stress can lower estradiol levels, so knowing cortisol levels can help to investigate the cause of low estradiol.  

Blood Sex Hormone Panel

Blood testing shows the amount of hormone in the blood at that specific time. Specifically, estrogen, progesterone, FSH, and LH can all be tested via blood tests.

Salivary Hormone Panel

A salivary hormone panel assesses levels of free hormones, including estradiol, at the tissue level. The tissues are where the hormones are active, so this measurement can be important when evaluating estradiol levels and their effects on the body.

Anti-Mullerian Hormone

Anti-Mullerian Hormone (AMH) is a marker that gives insight into the number of eggs a woman has left, suggesting how close to menopause she is. Studies show that AMH has an inverse relationship to estradiol levels, making this a valuable marker for investigating root causes of low or high estradiol.  

Thyroid Panel

Thyroid hormones can influence the menstrual cycle, including the production of estradiol. An under functioning thyroid gland can lead to abnormal estradiol levels.

GI-MAP

The GI-MAP by Diagnostic Solutions can give insight into the third phase of estrogen metabolism by providing the level of beta-glucuronidase. Beta-glucuronidase is the enzyme released by the microbes in the estrobolome that causes estrogen to be recycled or entered into the bloodstream.  

Integrative Medicine Approaches for Low Estradiol

Nutrition and Lifestyle

Phytoestrogens are chemical compounds found in certain foods that may activate the estradiol receptors and thus exhibit estrogenic activity. Good sources of phytoestrogens include legumes, such as soy and beans, and seeds, such as flaxseeds.

Regardless of the type of diet, ensuring adequate caloric intake is essential. Hormone production may slow in the presence of a chronic, significant caloric deficiency such as an eating disorder. While exercising is important, overexercising may also lead to low estrogen levels as it can also lead to a large reduction in calories.  

Complementary and Alternative Medicine

Phytoestrogens found in foods can also be found in certain botanicals. The European Journal of Obstetrics and Gynecology and Reproductive Biology reviewed 33 randomized control trials assessing phytoestrogen use in urogenital (urinary and vaginal) menopausal symptoms associated with low estradiol. Common phytoestrogen botanicals - Black Cohosh, Red clover, Hops, and others - were included in the review. Results showed improvements in urinary and vaginal symptoms and sexual function, suggesting that these botanicals may influence estradiol.  

Integrative Medicine Approaches for High Estradiol

Nutrition

A diet high in cruciferous vegetables may help in managing estradiol levels, as cruciferous vegetables contain the phytochemicals indole-3-carbinol and sulforaphane, which may support healthy Phase I and II estrogen detoxification.  

Complementary and Alternative Medicine

Various supplements can support all three estradiol metabolism phases and thus may help manage estradiol levels.

Phase I

In addition to eating cruciferous vegetables, Indole-3-carbinol and its product, 3,3’-diinolylmethane (DIM), can be taken in supplement form. Both may support healthy Phase I metabolism of estradiol.

Phase II

A B-complex, magnesium, choline, sulforaphane, and glutathione may be helpful to support methylation, a critical pathway in phase two of estradiol metabolism.  

Phase III

Calcium-d-glucurate and fiber supplements may support phase three estradiol metabolism, which occurs in the large intestine.

Summary

Estradiol is an essential hormone for women of all ages. As hormonal imbalances are common, assessing estradiol levels through functional medicine testing can be pivotal for a woman's health. Additionally, it's important to remember that estradiol's effects go beyond the reproductive system and can cause symptoms in other body systems that may not seem related. Integrative medicine approaches can be both helpful and effective in supporting balanced estradiol levels.