, , , ,

Lupus and Hormones

Never underestimate the power of hormones. These potent chemical messengers help regulate almost every function of the human body … including the autoimmunity.  Find out more about how they may influence lupus, and how they may lead to future treatments

 

Introduction to Lupus and Hormones

Hormones are chemical messengers that have a significant role in maintaining and regulating numerous bodily functions – from our growth and metabolic rates to our reproductive health. There are over one hundred hormones produced throughout the human body – from the brain to endocrine glands like the pituitary and adrenals.  Several hormones are known to affect the immune system, including the sex hormones estrogen and testosterone.  So, it is unsurprising that some could also be associated with autoimmune conditions, such as lupus.  For example, research has suggested that estrogen plays a role in both triggering the onset of lupus and increasing lupus symptoms.

Those with lupus should be aware of the implications of hormones on lupus activity, treatment, and their overall health.  As hormone levels fluctuate throughout life, so can lupus symptoms, disease activity, and risk.  There is so much about hormones and lupus that need to be studied, and the more that is learned, the more likely this knowledge may help with targeted treatments and more effective ways to perhaps delay or prevent the disease.

 

What role do hormones play in autoimmune disease and lupus?

Sex hormones may play a significant role in the development and severity of lupus for both sexes to varying degrees and both children and adults. Before puberty, both girls and boys are about equally at risk for lupus. However, once puberty hits and estrogen levels soar, girls become four times as likely as boys to develop lupus. Once women reach sexual maturity and through their 30s, they will be nine times as likely to develop lupus than men. While not as many men as women have lupus, they are still at higher risk for developing more severe lupus symptoms, like lupus nephritis.

Estrogen 

Both men and women have estrogen, though the levels are significantly higher for women in whom it plays a much more significant role. Aside from supporting sexual reproduction, estrogen plays a role in the immune system by doing the following:

  • triggering cytokine production and the inflammation response by activating T cells;
  • fostering B cell and autoantibody cell production, including anti-dsDNA; and
  • increasing reactivity to external and internal antigens, including the human endogenous retrovirus, often found with lupus.

Estrogen may have a role in why women tend to have a stronger immune system, in general, compared to men.  Unfortunately, this stronger immune response also might lead to a stronger autoimmune response.

Pregnancy puts women at a higher risk for lupus as estrogen levels increase to support a baby’s development. This may also increase the risk of a lupus flare, though these flares tend to be mild during pregnancy. Flares can also occur postpartum due to the sudden hormonal shifts that take place then.  Many doctors administer “stress doses” of corticosteroids to offset any rise in symptoms during and right after pregnancy.  This helps the body cope with the additional physical stress experienced during labor.

Keep in mind that just because a woman eventually goes through menopause, this does not eliminate the risk for lupus. Hormone replacement therapy replaces lost estrogen, and can put postmenopausal women at risk for lupus, and trigger an increase in cytokine production and the resulting inflammation.

Testosterone  

Like estrogen, both men and women have testosterone, though at varying levels and with differing effects. Testosterone acts as an immunosuppressant by decreasing pro-inflammatory cytokine production.  At the same time, men with lupus often experience worse lupus symptoms and often do not respond as well to immunosuppressants as women.  The reasons for this are still unclear, but testosterone may be involved.

 

Prolactin, Follicle-Stimulating Hormone, and Luteinizing Hormone

The pituitary gland, located in the base of the brain, is responsible for producing the sex hormones prolactin, follicle-stimulating hormone, and luteinizing hormone. These hormones can also trigger cytokine production. However, it is unclear if hormones cause the pituitary gland to dysfunctional or if glandular dysfunction causes hormones to misfire.

Prolactin triggers breast development during puberty and milk production during pregnancy. In lupus, prolactin is associated with an increase of anti-dsDNA antibodies as well. Therefore, pregnant women with abnormally high prolactin levels may have higher disease activity throughout pregnancy.

 

What other health risks do hormones pose for lupus?

While hormone therapy can work for some health conditions, a few can also pose risks for those with lupus:

Oral Contraceptives

While oral contraceptives prevent pregnancy by regulating or regulating hormones, they may have negative side effects for someone with lupus by increasing the risk for flares, migraines, high blood pressure, cardiovascular complications, blood clots, and stroke. The risk is even higher for smokers with lupus.

Hormone Replacement Therapy

Hormone replacement therapy (HRT) is often prescribed for menopausal women to treat hot flashes, night sweats, bone loss, and vaginal discomfort. However, HRT can also increase the risk for lupus flares, heart disease, blood clots, stroke, and breast cancer.

Testosterone Supplementation

Testosterone supplementation is used to treat sexual dysfunction, depression, fatigue, loss of muscle mass, and infertility in men. However, testosterone supplementation can also increase the risk for sleep apnea, acne, breast enlargement, blood clots, prostate dysfunction, and prostate cancer.

Some common lupus drug therapies act as hormones or may affect the hormones that the bosy normally produces. These include:

Corticosteroids

Corticosteroid drugs are actually analogues to some of the natural corticosteroid hormones produced by the body’s adrenal glands.  Puberty and menstruation may be delayed for girls with lupus on high corticosteroid therapy. In addition, post-pubescent girls with lupus may skip periods (amenorrhea), or they may cease altogether due to corticosteroids.

For men, high-dose corticosteroid therapy can result in lower testosterone levels and an increased risk of vasculitis.

Cyclophosphamide

About 31% of girls with lupus under 21 who take cyclophosphamide may have decreased ovarian reserves (egg supply), and about 11% will develop premature ovarian failure.  Adult women who take cyclophosphamide are at greater risk for decreased egg supply, ovarian failure, and infertility.

For boys with lupus, cyclophosphamide can reduce testicular size and sperm count at the onset of puberty and affect testosterone levels in adult men.

A healthcare practitioner should talk about the risk any of these treatments may pose based on overall health to avoid risks and complications, especially when dealing with something as sensitive as hormones and lupus.

 

In Conclusion

Hormones perform significant roles in our lives.  They regulate how our bodies function in almost every way – and this includes immunity and autoimmunity.  We still do not know how they influence or are influenced by lupus.  However, their effects are so profound that understanding them may lead researchers to develop better, more targeted therapies and improve the overall quality of life for those living with lupus.

 

References

Arnaud, L, Nordin, A., Lundhoms, H., Svenungsson, E., Hellabacher, E., Wikner, J., Zickert, A., & Gunnarsson, I. (2017). Effect of corticosteroids and cyclophosphamide on sex hormone profiles in male patients with systemic lupus erythematosus or systemic sclerosis. Arthritis & Rheumatology, 69(6), 1272-1279. https://doi.org/10.1002/art.40057

Khan, D. & Ahmed, S. (2016). The immune system is a natural target for estrogen action: Opposing effects of estrogen in two prototypical autoimmune diseases. Frontiers in Immunology, 6. https://doi.org/10.3389/fimmu.2015.00635

McMurray, R. & May, W. (2003). Sex hormones and systemic lupus erythematosus. Arthritis & Rheumatism, 48(8), 2100-2110. https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.11105

Mina, R. & Brunner, H. (2010). Pediatric lupus – Are there differences in presentation, genetics, response to therapy, damage accrual compared to adult lupus? Rheumatic Diseases Clinics of North America, 36(1), 53-80. https://dx.doi.org/10.1016%2Fj.rdc.2009.12.012

Shepherd, R., Cheung, A., Pang, K., Saffery, R., & Novakovic, B. (2021). Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.604000

Tuin, J., Sanders, J., buhl, B., van Beek, A., & Stegeman, C. (2013). Androgen deficiency in male patients diagnosed with ANCA-associated vasculitis: a cause of fatigue and reduced health-related quality of life? Arthritis Research & Therapy, 15(5). https://dx.doi.org/10.1186%2Far4297

 

Author: Liz Heintz

Liz Heintz is a technical and creative writer who received her BA in Communications, Advocacy, and Relational Communications from Marylhurst University in Lake Oswego, Oregon. She most recently worked for several years in the healthcare industry. A native of San Francisco, California, Liz now calls the beautiful Pacific Northwest home.

All images unless otherwise noted are property of and were created by Kaleidoscope Fighting Lupus. To use one of these images, please contact us at [email protected] for written permission; image credit and link-back must be given to Kaleidoscope Fighting Lupus.

All resources provided by us are for informational purposes only and should be used as a guide or for supplemental information, not to replace the advice of a medical professional. The personal views expressed here do not necessarily encompass the views of the organization, but the information has been vetted as a relevant resource. We encourage you to be your strongest advocate and always contact your healthcare practitioner with any specific questions or concerns.

Learn More