If you’re reading this article, it’s likely that your recent test results either showed elevated or low levels of estradiol. While this may sound concerning, rest assured that it’s a common marker we monitor and, importantly, one that can be addressed through personalised treatment plans.
Let’s take a closer look at what estradiol is, why optimal levels matter, and how it can impact your health.
What is Estradiol (E2)?
Estrogen is converted into three primary forms: estrone (E1), estradiol (E2), and estriol (E3), through the action of CYP enzymes.
Estrogens exert their effects by binding to estrogen receptors, found in various tissues, including:
- Reproductive tissues: e.g., the endometrium.
- Non-reproductive tissues: e.g., bone, breast tissue, and the brain.
Estrogen is essential for reproductive health, but its influence extends to the cardiovascular, skeletal, neurological, and immune systems. While it provides many protective effects, its levels must be well-regulated, as imbalances can lead to health issues such as estrogen dominance or deficiency.
Estradiol (E2) is the most potent and biologically active form of estrogen, playing a critical role in reproductive and overall health. It is primarily produced in the ovaries during the reproductive years, and smaller amounts are made in fat tissue and the adrenal glands. Estradiol levels fluctuate throughout the menstrual cycle and decline significantly after menopause.
E2 can be interconverted with E1, meaning imbalances in E1 can affect E2 levels, and vice versa.
Symptoms of High and Low E2 Levels
The luteal phase range for E2 is 1.8-4.5 ng/mg and the post-menopausal range is 0.2-0.7 ng/mg.
High E2 levels:
Estradiol may be high due to low progesterone (this may be due to lack of ovulation, over exercise, stress, poor HPO axis activation or under-eating), high histamine, poor estrogen detoxification, perimenopause, environmental toxins and endocrine disruptors and genetic SNPs (which can affect how estradiol is being detoxified).
In the early stages of perimenopause, it’s possible for estradiol reach higher levels than at any other time in your reproductive life. Testing your estrogen levels in perimenopause is therefore crucially important, especially if you are considering estrogen hormone replacement therapy.
Symptoms of high E2 levels include;
- Weight gain, especially in the hips and thighs
- Anxiety and depression
- Breast tenderness
- Irregular menstrual cycles
- Heavy menstrual cycles
- Brain fog
- Fatigue
- Fibroids and polyps.
Estradiol and cancer
As seen earlier, estrogen binds to estrogen receptors on cells. There are two types of estrogen receptors (ER) in the body, ER alpha and ER beta. The ER alpha are known to promote growth of tissue whilst the ER beta are thought to cause regression of growth. Estradiol has been shown to have a higher binding affinity for the ER beta, meaning at normal levels, it is helpful in preventing harmful growth of tissues.
However, at high levels, estradiol levels may contribute to estrogen positive cancers such as breast, ovarian, and uterine cancer and other conditions such as endometriosis and polycystic ovarian syndrome.
Low E2 Levels:
Chronically low estradiol has been associated with osteoporosis and heart disease. Low estradiol levels can occur due to menopause, surgical removal of the ovaries, undereating, overexercise, certain medical treatments such as birth control, hormonal disorders such as polycystic ovary syndrome (PCOS), thyroid issues and chronic stress.
Common symptoms of low E2 include:
- Bone loss
- Low libido
- Vaginal dryness
- Hot flashes and night sweats
- Fatigue and low energy
- Mood changes
- Weight gain, especially around the abdomen
- Insomnia
- Brain fog
Next steps
If you have not tested yet, our Advanced Hormone Test measures estradiol alongside your other estrogens, progesterone, testosterone and cortisol, plus the metabolites that show how well you are clearing them. If your results suggest high or low E2 levels, this will be addressed in your personalised health plan by one of our experienced nutritionists.
If you would like to learn more about your test results, remember you can purchase a 45-minute Hormone Health Consultation with your practitioner to discuss your results in more detail.
References
Correa, L. F., Zheng, Y., Delaney, A. A., Khan, Z., Shenoy, C. C., & Daftary, G. S. (2016). TGF-β Induces Endometriotic Progression via a Noncanonical, KLF11-Mediated Mechanism. Endocrinology, 157(9), 3332–3343. https://doi.org/10.1210/en.2016-1194
Diaz-Ruano, A. B., Martinez-Alarcon, N., Perán, M., Benabdellah, K., Garcia-Martinez, M. L. Á., Preda, O., Ramirez-Tortosa, C., Gonzalez-Hernandez, A., Marchal, J. A., & Picon-Ruiz, M. (2023). Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells. International journal of molecular sciences, 24(2), 1221. https://doi.org/10.3390/ijms24021221
Qureshi, R., Picon-Ruiz, M., Sho, M., Van Booven, D., Nunes de Paiva, V., Diaz-Ruano, A. B., Ince, T. A., & Slingerland, J. (2022). Estrone, the major postmenopausal estrogen, binds ERa to induce SNAI2, epithelial-to-mesenchymal transition, and ER+ breast cancer metastasis. Cell reports, 41(7), 111672. https://doi.org/10.1016/j.celrep.2022.111672
Qureshi, R., Picon-Ruiz, M., Aurrekoetxea-Rodriguez, I., Nunes de Paiva, V., D’Amico, M., Yoon, H., Radhakrishnan, R., Morata-Tarifa, C., Ince, T., Lippman, M. E., Thaller, S. R., Rodgers, S. E., Kesmodel, S., Vivanco, M. D. M., & Slingerland, J. M. (2020). The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development. Cell metabolism, 31(6), 1154–1172.e9. https://doi.org/10.1016/j.cmet.2020.05.008
Yu, K., Huang, Z. Y., Xu, X. L., Li, J., Fu, X. W., & Deng, S. L. (2022). Estrogen Receptor Function: Impact on the Human Endometrium. Frontiers in endocrinology, 13, 827724. https://doi.org/10.3389/fendo.2022.827724
Zheng, Y., Tabbaa, Z. M., Khan, Z., Schoolmeester, J. K., El-Nashar, S., Famuyide, A., Keeney, G. L., & Daftary, G. S. (2014). Epigenetic regulation of uterine biology by transcription factor KLF11 via posttranslational histone deacetylation of cytochrome p450 metabolic enzymes. Endocrinology, 155(11), 4507–4520. https://doi.org/10.1210/en.2014-1139
Zhu, B. T., Han, G. Z., Shim, J. Y., Wen, Y., & Jiang, X. R. (2006). Quantitative structure-activity relationship of various endogenous estrogen metabolites for human estrogen receptor alpha and beta subtypes: Insights into the structural determinants favoring a differential subtype binding. Endocrinology, 147(9), 4132–4150. https://doi.org/10.1210/en.2006-0113Ziegler, R. G., Fuhrman, B. J., Moore, S. C., & Matthews, C. E. (2015). Epidemiologic studies of estrogen metabolism and breast cancer. Steroids, 99(Pt A), 67–75. https://doi.org/10.1016/j.steroids.2015.02.015
