Autoimmunity & Infertility

Recently I’ve heard from quite a few women who are battling both autoimmunity and infertility and have therefore read both of my books (It Starts with the Egg for fertility and The Keystone Approach for autoimmunity).

 

I’ve been looking into the connection between the two issues and wanted to share what I’ve learned from the scientific studies, and my own experience.

 

(A brief introduction for those of you who don’t know me yet:  I have psoriatic arthritis, celiac, and mild Graves thyroid autoimmunity. I successfully tackled premature ovarian insufficiency in my late 20s and now have two little boys, carried by a gestational surrogate due to the severity of my psoriatic arthritis at the time.  I am a science writer with a degree in molecular biology and biochemistry, but I previously spent many years working as a patent lawyer analyzing and writing about the scientific evidence for biologic medications).

How Does Autoimmunity Contribute to Infertility?

The well-known reasons:
-Inflammation itself likely contributes to poor egg quality, as we see in endometriosis.  We can help to calm this inflammation through diet  and supplements such as Omega-3 fats and alpha-lipoic acid.
-Thyroid autoimmunity also compromises fertility as explained in It Starts with the Egg.  This can be tackled with Synthroid treatment and dietary changes to remove some of the potential autoimmune triggers (such as gluten and dairy sensitivity).
What no one is talking about yet: 
It seems that in women with certain autoimmune diseases, there is often compromised adrenal function, reflected in reduced production of DHEA. (This has been reported in those with thyroid autoimmunity, Addison’s, psoriatic arthritis, and RA).

 

The ovaries use DHEA from the adrenals to produce testosterone needed for early follicle development, so a depletion of DHEA leads to diminished ovarian reserve/premature ovarian insufficiency/premature ovarian failure. This shows up as low AMH, low antral follicle count, and failed IVF cycles with very few eggs retrieved.

DHEA, Fertility & Autoimmunity

If you have both autoimmune disease and infertility (or recurrent miscarriage)  I highly recommend getting your DHEA-S level tested (this is more accurate than testing DHEA itself).  You can order this test yourself through various online providers, include Life Extension in the U.S. and MediChecks in the UK.  If it is low, it may make sense to supplement with DHEA.  (See Chapter 9 of It Starts with the Egg and my post on Questions About DHEA for optimal levels and dosage.).

 

It is also helpful to find out your testosterone level. It appears that inflammation can potentially interfere with the conversion of DHEA to testosterone, so you may have a normal DHEA level but low testosterone.  If that is the case, talk to a knowledgable reproductive endocrinologist about your options. They may recommend a higher dose of DHEA, or directly supplementing with testosterone itself (e.g. with a testosterone cream).

Side Benefits of DHEA for Autoimmunity

As a bonus, DHEA – might- also benefit your autoimmune condition.  DHEA can modulate the immune system and shift the balance between different immune cells.  It is not entirely clear what the net result would be for inflammation, but it is likely beneficial (study).  I have recently started taking it myself again, because I remember that when I was doing IVF prep I generally felt better overall. (Testing also confirmed that my DHEA level was still rather low).

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 Selected References

Szlendak-Sauer, K., Jakubik, D., Kunicki, M., Skórska, J., & Smolarczyk, R. (2016). Autoimmune polyglandular syndrome type 3 (APS-3) among patients with premature ovarian insufficiency (POI). European Journal of Obstetrics & Gynecology and Reproductive Biology203, 61-65.

Hedman, M., & Nilsson, E. (1992). Low blood and synovial fluid levels of sulpho-conjugated steroids in rheumatoid arthritis. Clinical and experimental rheumatology10(1), 25-30.

Masi, A. T., Rehman, A. A., Cutolo, M., & Aldag, J. C. (2014). Do women with premenopausal‐onset rheumatoid arthritis have relative insufficiency or imbalance of adrenocortical steroids?. Annals of the New York Academy of Sciences1317(1), 7-16.

Gleicher, N., Kushnir, V. A., Weghofer, A., & Barad, D. H. (2016). The importance of adrenal hypoandrogenism in infertile women with low functional ovarian reserve: a case study of associated adrenal insufficiency. Reproductive Biology and Endocrinology14(1), 23.

Gleicher, N., Seier, K., Kushnir, V. A., Weghofer, A., Wu, Y. G., Wang, Q., … & Barad, D. H. (2016). Associations between peripheral androgens and cortisol in infertile women. The Journal of steroid biochemistry and molecular biology158, 82-89.

Husebye, E. S., & Løvås, K. (2009). Immunology of Addison’s disease and premature ovarian failure. Endocrinology and metabolism clinics of North America38(2), 389-405.

Straub, R. H., Schölmerich, J., & Zietz, B. (2000). Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory diseases–substitutes of adrenal and sex hormonesHormonersatz mittels DHEA plus Glukokortikoide in der Therapie von Patienten mit chronisch entzündlichen Erkrankungen. Zeitschrift für Rheumatologie59(2), 108-118.

See also: my collection of randomized studies of DHEA for Infertility