Autoimmune diseases are becoming increasingly prevalent, especially among women. In fact, the American Autoimmune Related Diseases Association estimates that 80% of the 24 million Americans with autoimmune diseases are women, and 85% or more of those with multiple autoimmune diseases are female.
This gender divide in those affected by autoimmune diseases leads to the inevitable speculation that sex hormones, which differ between men and women, may play a role in autoimmune disease development.
What Are Autoimmune Diseases?
An autoimmune disease occurs when your immune system begins attacking your body instead of foreign contagions, such as viruses and bacteria.
The immune system works by marking foreign proteins and then destroying them. However, for those with an autoimmune disease, the immune system mistakenly marks proteins that are a part of you. Then, when the immune system sets out to destroy any marked proteins, it ends up attacking itself.
Sex hormones appear to play a role in autoimmune diseases since these diseases typically fluctuate with hormonal changes. For example, some instances that cause autoimmune diseases to flare up include the menstrual cycle, pregnancy, or using oral contraceptives. All of these instances result in dramatic changes in female sex hormone levels.
The Role of Female Hormones
When looking at sex hormones, testosterone typically has an immunosuppressive effect, whereas estrogen has an immunoenhancing effect. Just two of the roles of estrogen in the immune system include regulating the immune response and inducing T cells (a component of the immune system) to home in on marked proteins.
Itâ€™s not just estrogen that impacts the immune system, either, with progesterone helping to inhibit the inflammatory innate immune response.
This shows that female hormones play a vital role in the immune system, and how effectively they accomplish this depends on their concentration in the body.
Hormonal Changes in Women
Women undergo at least two significant endocrinological changes in their life, puberty and menopause. In addition, women who become pregnant also undergo significant hormonal changes, with breastfeeding adding an extra component for those who do it.
In addition to impacting your mood, these hormonal changes are also extremely taxing on the immune system because of the interactions between the innate and adaptive immune systems, hormonal milieu, and the pro- and anti-inflammatory cytokines.
To show how these hormonal changes affect a body, a study found that women around the age of 50 had neutrophil percentages that dropped while lymphocyte percentages rose. This makes perimenopausal women more susceptible to lymphocyte-mediated autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis.
Autoimmune Diseases by Life Stage
Many autoimmune diseases in women increase and decrease in risk based on the life stage a woman is in and the corresponding hormones they produce more or less of.
For example, multiple sclerosis (MS) is most prevalent among women of reproductive age and affects twice as many women as men. Studies have also shown that MS is closely linked to the female hormonal and reproductive cycles. Additionally, disease severity typically increases in postmenopausal women when estrogen levels decline.
Even more, MS relapses reduce during pregnancy, and this is because the female body produces more sex hormones during this time. This evidence shows the connection between hormone deficiency and MS development and how HRT may be able to address the symptoms.
Other autoimmune diseases have shown peaks during certain ages for women, whereas men typically show an increasing incidence with age. For example, with systemic lupus erythematosus (SLE), there is a peak in incidence for women between the ages of 35-39 and 55-59. In contrast, men show increasing incidence after 60, with a peak at 70+ years.
Beside estrogen and progesterone, a hormone that is typically low in women with autoimmune diseases is DHEA, which is a natural steroid produced by the reproductive organs, adrenal glands, and the brain.
DHEA is used to make testosterone and estrogen, but it is also known to have anti-inflammatory effects. When it comes to autoimmune diseases, inflammation is often a key component, and this decline in DHEA may be what leads to increased inflammation.
One study examining DHEA levels and Sjogrenâ€™s disease found that there was a strong correlation between low DHEA and Sjogrenâ€™s symptoms. The researchers concluded that the symptoms of Sjogrenâ€™s syndrome appeared due to low sex hormones, and supplementing with DHEA allowed the body to turn it into estrogen, improving the participantâ€™s symptoms.
Hormone Replacement Therapy for Autoimmune Disorders
Hormone replacement therapy (HRT) is a treatment method that, much as the name suggests, supplements the body with hormones to balance any declining levels.
There are many different hormones available in hormone replacement therapy, including estrogen, testosterone, and progesterone.
The preferred hormone for treatment will typically depend on the autoimmune disease, as different diseases result from different hormone declines. However, in most cases, the reduction is of a female sex hormone, which can include the class of estrogens (e.g., estradiol, estrone, and estriol) and progesterone.
While female sex hormones appear in the greatest quantity in women, men also utilize these hormones, meaning they can also experience the effects when these hormones become too low.
For the autoimmune disease of MS, studies have found that estriol was the most beneficial estrogen to supplement, with women who have relapsing-remitting MS experiencing a significant reduction of relapse rates when given standard of care medication in addition to oral estriol.
For rheumatoid arthritis (RA), another type of autoimmune disease, research has found that hormone replacement therapy with progesterone and estrogen can help to reduce the overall activity of RA.
These studies show that hormone replacement therapy can be effective in treating or relieving symptoms of autoimmune diseases, especially in women.
However, in order to see the most benefit, your doctor will need to consider the autoimmune disease you have, and they may also wish to discuss when you notice flare-ups in your symptoms. Your doctor can also test your hormone levels to see if there are any below-normal levels, and this information can help your doctor determine which hormone needs supplementation.
There are some risks to consider in regard to hormone treatment for autoimmune diseases. For instance, some studies have reported that while HRT can help to improve the overall disease, flare-ups, when they do occur, are much more intense.
Additionally, those with autoimmune disorders may need long-term HRT to manage their condition, but using hormones long-term is associated with some risks, including high blood pressure, blood clots, and increased risk of some cancers.
These are both things to discuss with your doctor to determine if the potential risks are worth the benefits afforded by HRT.
Desai, M., & Brinton, R. (2019). Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan.Â Frontiers In Endocrinology,Â 10. doi: 10.3389/fendo.2019.00265
About Autoimmunity – Autoimmune Association. (2022). Retrieved 18 August 2022, from https://autoimmune.org/resource-center/about-autoimmunity/
Taneja, V. (2018). Sex Hormones Determine Immune Response.Â Frontiers In Immunology,Â 9. doi: 10.3389/fimmu.2018.01931
Hall, O., & Klein, S. (2017). Progesterone-based compounds affect immune responses and susceptibility to infections at diverse mucosal sites.Â Mucosal Immunology,Â 10(5), 1097-1107. doi: 10.1038/mi.2017.35
Brandt, J., Priori, R., Valesini, G., & Fairweather, D. (2015). Sex differences in SjÃ¶grenâ€™s syndrome: a comprehensive review of immune mechanisms.Â Biology Of Sex Differences,Â 6(1). doi: 10.1186/s13293-015-0037-7
Chen, Y., Zhang, Y., Zhao, G., Chen, C., Yang, P., Ye, S., & Tan, X. (2016). Difference in Leukocyte Composition between Women before and after Menopausal Age, and Distinct Sexual Dimorphism.Â PLOS ONE,Â 11(9), e0162953. doi: 10.1371/journal.pone.0162953
Belman, A., Krupp, L., Olsen, C., Rose, J., Aaen, G., & Benson, L. et al. (2016). Characteristics of Children and Adolescents With Multiple Sclerosis.Â Pediatrics,Â 138(1). doi: 10.1542/peds.2016-0120
Bove, R., Healy, B., Secor, E., Vaughan, T., Katic, B., & Chitnis, T. et al. (2015). Patients report worse MS symptoms after menopause: Findings from an online cohort.Â Multiple Sclerosis And Related Disorders,Â 4(1), 18-24. doi: 10.1016/j.msard.2014.11.009
Runmarker, B., & Andersen, O. (1995). Pregnancy is associated with a lower risk of onset and a better prognosis in multiple sclerosis.Â Brain,Â 118(1), 253-261. doi: 10.1093/brain/118.1.253
Jarukitsopa, S., Hoganson, D., Crowson, C., Sokumbi, O., Davis, M., & Michet, C. et al. (2015). Epidemiology of Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus in a Predominantly White Population in the United States.Â Arthritis Care &Amp; Research,Â 67(6), 817-828. doi: 10.1002/acr.22502
Voskuhl, R., Wang, H., Wu, T., Sicotte, N., Nakamura, K., & Kurth, F. et al. (2016). Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial.Â The Lancet Neurology,Â 15(1), 35-46. doi: 10.1016/s1474-4422(15)00322-1
Holroyd, C., & Edwards, C. (2009). The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus.Â Climacteric,Â 12(5), 378-386. doi: 10.1080/13697130903025449
About Dr. Mel Irvine
Dr. Mel Irvine, DNP and Clinical Sexologist specializes in sexual medicine and beauty in Fort Myers Florida. She earned her Doctor of Nursing Practice at Florida Gulf Coast University and her masterâ€™s degree at the University of Alabama at Birmingham. In 2018, she completed a preceptorship at San Diego Sexual Medicine with Dr. Irwin Goldstein and obtained her clinical sexologist certification from STII with Dr. Carol Clark. She is passionate about working with singles and couples to learn and explore their sexuality and sexual health needs through providing a comfortable and nonjudgmental atmosphere. As a provider she offers a balanced and holistic approach that encompasses a multimodal care delivery model.