The Key to Autoimmunity: Do Hormones Have Answers?

Awaiting a cure, autoimmune patients are knocked down by numerous triggers outside of their control. Unable to recognize friend from foe, your patient’s immune systems attack their own organs and tissues without warning. The gender gap is great in rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). Women make up 80% of individuals diagnosed with chronic inflammatory autoimmune diseases, marked by fluctuating symptoms that are difficult to diagnose.

Although controversial in these conditions, hormones have an important role to play in understanding autoimmunity. An estrogen link exists. Studying the female sex hormone’s effect on the immune system revealed a connection between peaks or valleys of estrogen levels and autoimmunity. When combined with aggravating factors (genetic predisposition, infection, stress), pivotal milestones like puberty, pregnancy, and menopause underline hormonal shifts that could impact a woman’s immune system forever.

Is estrogen the enemy? Not quite. MS is characterized by attacks on the central nervous system by antibodies, damaging myelin and resulting in brain signaling issues. As an immune modulator, estriol may assist with the process of remyelination, helping repair the myelin sheaths protecting at risk nerves from the disease. Studies suggest estriol may also decrease the inflammatory response in MS, but the methodology is not fully understood.

Incidence of RA peaks during perimenopause, a time of estrogen deficiency. RA causes painful swelling and inflammation by acting on joints and muscles. After menopause, an osteoporosis diagnosis is concerning. For postmenopausal RA patients in particular, bone loss and fracture risk combined with joint deformity can be debilitating. Studies interpreting the effect of hormone replacement therapy on RA patients have not only documented improvements in bone mineral density but in slowing disease progression as well.

Data continues to be mixed concerning exogenous estrogen replacement therapy in SLE, but dehydroepiandrosterone (DHEA) has demonstrated encouraging results. In a study investigating 120 women with active mild to moderate SLE, 200 mg of DHEA daily decreased the number of SLE flares over the course of six months. Results from the study also suggest an impact on disease management. Promising improvements in SLE patient day to day functioning via global assessment means potential relief from the fatigue, rash, and pain associated with the diagnosis.

Even if hormone therapy may not have a starring role in autoimmune remedies today, you and your patients have much to gain by pursuing its part.  Regimens with the potential to minimize flares and maximize symptom management should be prioritized. Finding care that limits risk while slowing disease progression could give your autoimmune patients the daily freedoms they deserve.

References

  1. Ali, Emad S. MD1; Mangold, Cheyenne MSIII2; Peiris, Alan N. MD, PhD, FRCP(London)3 Estriol: emerging clinical benefits, Menopause: September 2017 – Volume 24 – Issue 9 – p 1081-1085 doi: 10.1097/GME.0000000000000855
  2. Angum F, Khan T, Kaler J, Siddiqui L, Hussain A. The Prevalence of Autoimmune Disorders in Women: A Narrative Review. Cureus. 2020 May 13;12(5):e8094. doi: 10.7759/cureus.8094. PMID: 32542149; PMCID: PMC7292717.
  3. Avila M, Bansal A, Culberson J, Peiris AN. The Role of Sex Hormones in Multiple Sclerosis. Eur Neurol. 2018;80(1-2):93-99. doi: 10.1159/000494262. Epub 2018 Oct 19. PMID: 30343306.
  4. Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002 Nov;46(11):2924-7. doi: 10.1002/art.10615. PMID: 12428233.
  5. D’Elia HF, Larsen A, Mattsson LA, Waltbrand E, Kvist G, Mellström D, Saxne T, Ohlsson C, Nordborg E, Carlsten H. Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis. J Rheumatol. 2003 Jul;30(7):1456-63. PMID: 12858441.
  6. Desai MK, Brinton RD. Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan. Front Endocrinol (Lausanne). 2019 Apr 29;10:265. doi: 10.3389/fendo.2019.00265. PMID: 31110493; PMCID: PMC6501433.
  7. Holroyd CR, Edwards CJ. The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus. Climacteric. 2009 Oct;12(5):378-86. doi: 10.1080/13697130903025449. PMID: 19591008.
  8. Lateef A, Petri M. Hormone replacement and contraceptive therapy in autoimmune diseases. J Autoimmune. 2012 May;38(2-3):J170-6. doi: 10.1016/j.jaut.2011.11.002. Epub 2012 Jan 18. PMID: 22261500.
  9. Peterson C, Strommen L. Autoimmune Disease: An Overview. Connections. Women’s International Pharmacy.  
  10. Sammaritano LR. Menopause in patients with autoimmune diseases. Autoimmun Rev. 2012 May;11(6-7):A430-6. doi: 10.1016/j.autrev.2011.11.006. Epub 2011 Nov 18. PMID: 22120060.
  11. Sapir-Koren R, Livshits G. Postmenopausal osteoporosis in rheumatoid arthritis: The estrogen deficiency-immune mechanisms link. Bone. 2017 Oct;103:102-115. doi: 10.1016/j.bone.2017.06.020. Epub 2017 Jun 27. PMID: 28666971.

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