While you may often think of estrogen for its relationship to female fertility, estrogen plays a variety of other roles in the body, including an important role in inflammation and the immune response. Estrogen helps direct immune cells to respond appropriately when bacteria, viruses, or other foreign microbes are detected in the body. However, high estrogen levels can contribute to elevated inflammation and may even exacerbate autoimmune activity, while low estrogen levels may make individuals more susceptible to things like viral infections and allergies. Ultimately, balance is key when it comes to estrogen levels and your immune system function.
Estrogen's Function: More Than Just Reproductive Health
Estrogen is well-known for its important role in female reproductive health, being responsible for the development of female secondary sex characteristics, regulation of the menstrual cycle, and fertility. However, the presence of estrogen receptors outside of the reproductive system highlights the widespread impact estrogen has across the body as a whole. Estrogen receptors are found in the bone, brain, liver, cardiovascular system, skin, colon, and even the salivary glands.
Estrogen also impacts metabolic health, with estrogenic activity in the liver, adipose tissue, skeletal system, and immune cells contributing to insulin sensitivity as well as regulating fat accumulation and inflammation. The loss of estrogen that comes with menopause or ongoing low levels of estrogen in reproductive years tends to promote metabolic dysfunction, showing how important estrogen is for metabolism.
Understanding estrogen levels and fluctuations, then, is important for much more than just menstrual cycle regulation. Levels may impact everything from inflammation to fat storage to cardiovascular function, which is why a functional medicine approach that considers the body as a whole is important for optimal health and well-being.
The Positive Side: Estrogen as an Immune Enhancer
Estrogen’s immune-boosting properties can be beneficial in protecting against certain types of infections, such as viral infections. Studies have found that estrogen can enhance levels of circulating antibodies, helping with a stronger adaptive response to infections.
As women progress through their menstrual cycle, estrogen levels naturally fluctuate, with the lowest levels occurring around the start of menstruation. It is during this time of low estrogen that women have been found to experience low-grade inflammation and a rise in inflammatory markers such as hs-CRP versus at other points in their cycle when the protective role of estrogen is more prevalent.
Additionally, there’s evidence of estrogen as a natural defense mechanism when pregnancy is considered. During pregnancy, estrogen levels are at their peak, and simultaneously, certain dangerous inflammatory pathways are suppressed. At the same time, there is evidence of an increased production of infection-neutralizing antibodies, providing a safer mechanism of immune protection for the mom and developing baby.
The Flip Side: Increased Vulnerability to Autoimmune Disorders
With the ability of estrogen to stimulate the immune system also comes the risk of over-stimulation in certain environments. Prolonged high levels of estrogen may stimulate certain immune markers for autoimmune disease for several reasons. Estrogen can enhance antibody production through its direct communication with T and B lymphocytes and may also have an impact on gene expression related to immune function.
It is possible that the impact of estrogen on the immune system contributes to the high prevalence of autoimmune disorders in women, with 80% of diagnoses occurring in women. Women are most frequently diagnosed with autoimmune symptoms in premenopausal years during times of higher estrogen, further highlighting the potential for estrogen to create an environment where immune modulation may go awry. However, it’s important to remember that estrogen can be both pro-inflammatory and anti-inflammatory, and the bigger picture of hormone balance in the body as a whole must be considered when looking at estrogen’s potential to potentiate autoimmune diseases in women.
Life Phases: How Estrogen Levels Influence Immunity Across a Woman's Life
Estrogen levels fluctuate widely throughout a woman’s life span, and with those fluctuations may also come changes in the dynamics of the immune system. Research shows that women’s immune systems are generally strongest during reproductive years when estrogen is at its peak.
There are also variations seen within the menstrual cycle itself, with lower levels of different immune markers (such as cytokines and antibodies) in the luteal phase when estrogen levels tend to be lower. While this may mean women are slightly more susceptible to infection during their luteal phase; it also may mean that women with autoimmune conditions can experience some relief during the luteal phase due to lowered antibody production.
During pregnancy and postpartum, women experience changes in estrogen and other hormone levels and immune resilience changes as well. There is a reduction in pro-inflammatory immune processes while an increased tolerance for antigens from the developing baby and an increase in anti-inflammatory cytokines also occur. It’s likely that the gut microbiome also helps modulate these immune changes alongside rising hormone levels.
As estrogen levels decline during and after menopause, there is evidence that with that decline comes more changes in immune resilience. Postmenopausal women may be more susceptible to colds, the flu, and other viruses than premenopausal women. Additionally, inflammation tends to be higher in postmenopausal women as the protective benefits of estrogen are lost, setting postmenopausal women up for a higher risk of cardiovascular disease, insulin resistance, and metabolic dysfunction.
Addressing Other Hormones: Progesterone and Testosterone
While estrogen can stimulate the immune system, progesterone tends to decrease the inflammatory response, and activate anti-inflammatory T cells and encourage mucosal cell repair, offsetting the impact of estrogen on immune activity. Similarly to estrogen, there are progesterone receptors found on many different types of immune cells, including macrophages, B and T lymphocytes, and natural killer cells. Testosterone can also have an inhibitory effect on the immune system, which may also account for why men tend to have lower rates of autoimmunity while also being more susceptible to colds and other infections.
Maintaining a hormonal balance is thus also important for immune balance; a relative estrogen dominance or low hormone levels overall can lead to undesirable changes in the immune system, setting women up for a higher risk of autoimmune activity and other issues.
Functional Medicine Lab Testing: Deciphering the Estrogen-Immunity Connection
To best understand if your estrogen levels are impacting your immune function in an undesirable way, functional medicine lab testing can be used to assess estrogen levels, levels of other hormones, and the presence of inflammation and immune dysfunction. For example, the Female Serum Hormones Basic Profile by ZRT Laboratory includes estrogens, progesterone, and testosterone can help bring to light any imbalances between sex hormones that may be interrupting the regulation of immune function. Additionally, evaluating for inflammation through tests like hs-CRP, an Omega-3 index, or autoimmune markers can help create a bigger picture of estrogen-immune dynamics that may be at play.
Key Takeaways: Understanding the Estrogen-Immunity Connection
Women’s hormone health is important for many different areas of health beyond fertility, including immune health. Understanding how your hormones may impact inflammation and the immune response is an important component of supporting hormone health throughout the life cycle. Women with autoimmune conditions can benefit from optimizing their hormone health to help ensure estrogen imbalances aren’t worsening their symptoms. Ultimately, it’s all about balance when it comes to the relationship between estrogen and immunity.
Lab Tests in This Article
Abildgaard, J., Tingstedt, J., Zhao, Y., Hartling, H. J., Pedersen, A. T., Lindegaard, B., & Dam Nielsen, S. (2020). Increased systemic inflammation and altered distribution of T-cell subsets in postmenopausal women. PLOS ONE, 15(6), e0235174. https://doi.org/10.1371/journal.pone.0235174
Angum, F., Khan, T., Kaler, J., Siddiqui, L., & Hussain, A. (2020). The Prevalence of Autoimmune Disorders in Women: A Narrative Review. Cureus, 12(5). https://doi.org/10.7759/cureus.8094
Christie, Dr. J. (2022c, August 23). Weight Gain, Low Libido, And Headaches Are Signs You Aren’t Metabolizing This Hormone Properly. Rupa Health. https://www.rupahealth.com/post/how-to-know-if-your-body-is-metabolizing-estrogen-properly
Cloyd, Dr. K. (2023, October 24). Progesterone Power: The Unsung Heroine in Women’s Health and Mood. Rupa Health. https://www.rupahealth.com/post/progesterone-power-the-unsung-heroine-in-womens-health-and-mood
Desai, M. K., & Brinton, R. D. (2019). Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan. Frontiers in Endocrinology, 10(265). https://doi.org/10.3389/fendo.2019.00265
Easthope, A. (2022, May 3). Women Need Testosterone Too. Watch For These 6 Symptoms Of Low Testosterone. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-approach-to-low-female-testosterone
Eyster, K. M. (2016). The Estrogen Receptors: An Overview from Different Perspectives. Methods in Molecular Biology (Clifton, N.J.), 1366, 1–10. https://doi.org/10.1007/978-1-4939-3127-9_1
Fuhler, G. M. (2020). The immune system and microbiome in pregnancy. Best Practice & Research Clinical Gastroenterology, 44-45, 101671. https://doi.org/10.1016/j.bpg.2020.101671
Gameiro, C. M., Romão, F., & Castelo-Branco, C. (2010). Menopause and aging: Changes in the immune system—A review. Maturitas, 67(4), 316–320. https://doi.org/10.1016/j.maturitas.2010.08.003
Harding, A. T., & Heaton, N. S. (2022). The Impact of Estrogens and Their Receptors on Immunity and Inflammation during Infection. Cancers, 14(4), 909. https://doi.org/10.3390/cancers14040909
Hughes, S. M., Levy, C., Katz, R., Lokken, E., Anahtar, M. N., Melissa Barousse Hall, Bradley, F., Castle, P. E., Cortez, V., Doncel, G. F., Fichorova, R. N., Fidel, P. L., Fowke, K. R., Francis, S. C., Ghosh, M., Hwang, L. Y., Jais, M., Jespers, V., Vineet Joag, & Kaul, R. (2022). Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data. BMC Medicine, 20(1). https://doi.org/10.1186/s12916-022-02532-9
Johns Hopkins Medicine. (n.d.). Estrogen’s Effects on the Female Body. Www.hopkinsmedicine.org. https://www.hopkinsmedicine.org/health/conditions-and-diseases/estrogens-effects-on-the-female-body#:~:text=In%20addition%20to%20regulating%20the
Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013). The Role of Estrogens in Control of Energy Balance and Glucose Homeostasis. Endocrine Reviews, 34(3), 309–338. https://doi.org/10.1210/er.2012-1055
Moulton, V. R. (2018). Sex Hormones in Acquired Immunity and Autoimmune Disease. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.02279
Orbeta, R. (2022, April 1). 8 Signs And Symptoms Of An Autoimmune Disease. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-approach-to-autoimmune-disease
Ramírez-de-Arellano, A., Gutiérrez-Franco, J., Sierra-Diaz, E., & Pereira-Suárez, A. L. (2021). The role of estradiol in the immune response against COVID-19. Hormones, 20(4), 657–667. https://doi.org/10.1007/s42000-021-00300-7
Robinson, D. P., & Klein, S. L. (2012). Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Hormones and Behavior, 62(3), 263–271. https://doi.org/10.1016/j.yhbeh.2012.02.023