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Estrogens and the Immune System

June 12 2015 7:00 AM ET — via RheumReports RheumReports

In addition to having a rheumatology-focused practice, I am a certified menopause practitioner so this session generated great interest for me. Joint pain and worsening of chronic inflammatory conditions is commonly seen with fluctuations in hormone levels. This phenomenon applies to both androgens and estrogens, and both aspects were covered in this EULAR 2015 session.

Androgen levels are found to be low in tissues where there is inflammation. TNF activates aromatase resulting in a decrease in the production of the activated form of testosterone (dihydrotestosterone) and an increase in the negatively acting metabolite of estradiol (16 alpha hydroxyestrone) which can generate further inflammation. DHEA levels can also be reduced in response to TNF.

There are limited studies evaluating the impact of testosterone or DHEA supplementation in women and men and the results appear to be mixed. Anecdotally, a physiatrist in Ontario is measuring testosterone levels in his chronic pain patients and finding that supplementation, when levels are low, is helpful for both pain control and energy. It is important to note that levels of excessive testosterone as seen in women with PCOS, increases inflammation so finding the right balance is important.

In regards to estrogen, we now know that during pregnancy, a woman passes through periods of increased inflammation during the first and third trimester and there is an anti-inflammatory phase during the second trimester when she generally feels the healthiest. This inflammatory state is needed for ovulation and implantation as well as for parturition. Even the use of NSAIDs can reduce a woman's ability to become pregnant and maintain pregnancy in the first trimester. This effect is seen to a greater extent in those without chronic inflammatory disease. 

Estradiol's effects on cytokine production vary with cell type. Generally, higher levels of estradiol inhibit TNF, IL-6 and IL-1beta along with stimulating B-cell activation. This is why diseases which are B-cell mediated such as SLE worsen in pregnancy. In menopause, when estradiol levels are low, there is an activation of T-cells which can lead to flares of T-cell driven diseases such as RA. The use of oral contraceptives and hormone replacement therapy in menopause is not thought to increase estradiol levels sufficiently from baseline levels to have benefit in the small studies that have been done to date. Anecdotally, women who receive hormone replacement therapy in my practice do indicate a reduction in joint pain and inflammation. More studies need to be done in this area. Anyone interested in this research? Let me know as I have lots of ladies with hot flashes, night sweats and joint pain who would be interested!


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About the Author

Carolyn Whiskin
Carolyn Whiskin

Carolyn Whiskin, BSc. Phm is currently the director of pharmacy programs for the Charlton Centre for Specialized Treatments in Hamilton, Ontario. She also practices pharmacy at Brant Arts Dispensary in Burlington, Ontario and is the pharmacist representative to the Ontario Rheumatology Association’s Model of Care committee.

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