Pregnancy and Autoimmune: How does it relate?

Pregnancy and Autoimmune: How does it relate?

This topic is near and dear to my heart as many of my conditions developed during or after pregnancy.  There is such a strong connection between the immune system and the endocrine system (hormones), and a reason why autoimmune conditions are so highly prevalent in women.  Before I begin to talk about the details, I want to give you a basic explanation of the immune system, which can be quite complex.  To try to simplify it, we have two major pathways:

  1. Cellular immunity (T-helper 1) 
  2. Humoral immunity (T-helper 2)

T-helper cells are a type of cell within the immune system that when they are activated signal other immune cells to “attack” the invader.  They are categorized differently based on how they are activated and what they release to kill:

  • Th1 pathway is activated by intracellular organisms and secrete certain immune cells to kill the organisms.
  • Th2 pathway is activated in response to antigenic stimuli from an extracellular organism and leads the body to secrete a different set of immune cells, and support the function of antibody-producing B cells.

Evidence has accumulated from animal models and human studies to suggest that Th1 cells are involved in the development of organ-specific autoimmune diseases, such as Hashimoto’s, MS, rheumatoid arthritis, and type 1 diabetes.  In these conditions Th1 is considered pathogenic or “bad” whereas Th-2 cells are more protective.  By contrast, Th2-cell predominance was found in patients with lupus, atopic dermatitis, and allergic diseases.

So why am I bringing all this up and how does it relate to pregnancy?

Levels of estrogen before and after menopause and levels of estriol and progesterone during pregnancy appear to affect autoimmune diseases.

Estrogen appears to push the immune system in the direction of the proinflammatory Th1 pathways, EXCEPT during pregnancy.  Because pregnancy is actually a high-estriol/high-progesterone state, estriol, functionally a weak estrogen, and progesterone clearly has anti-estrogen properties – we actually see an improvement because estrogen levels are actually low.  This is the potential reason why autoimmune diseases that involve over-expression of Th1 (e.g., rheumatoid arthritis, multiple sclerosis) frequently “go away” during pregnancy but “come back” during postpartum periods.

Thus, pregnancy appears to represent a unique situation for the immune system, switching from a Th1-dominant environment to an often Th2-dominant environment.

Although it has been almost universally held that pregnancy is a “high estrogen state,” it is in fact a time when ovarian production of hormones is suppressed and placental production of estrogens, primarily estriol, and progesterone is high. Estriol may block the effects of estradiol on the mother’s immune system, just as it blocks the negative effects of estrogen for the fetus. Progesterone has been shown to stimulate the Th2 system, which is responsible for activating B-cells and down-regulating Th1.

Rheumatoid Arthritis and MS improve during pregnancy as estriol and progesterone may function to inhibit presentation of antigens to Th1 cells, and increases the death (apoptosis) of activated immune cells.  Lupus a disease of up-regulated Th2, is variable in its response to pregnancy, sometimes getting better but often getting much worse.

In some autoimmune diseases, estrogen is thought to have a dual effect, where too much or too little estrogen may be equally detrimental to the normal functioning of the immune system. In any event, it would appear that the relationship of estrogen to diseases of autoimmunity is complex and not fully worked out at this point, and the presence of an estrogen-dominant environment that we live in further complicates the immune system’s attempts to shut down the reactive furnace.

This is why I try and avoid estrogens as much as possible with my Hashimoto’s as I don’t want to exacerbate the response!

References:

Druet P, Sheela R, Pelletier L. Th1 and Th2 cells in autoimmunity. Clinical And Experimental Immunology[serial online]. July 1995;101 Suppl 1:9-12.

Jones, D. et al.  Institute for Functional Medicine (2010).  Textbook of Functional Medicine. Gig Harbor, WA.: Institute for Functional Medicine.

Zhang P, Chen H, Tu Y, et al. Analysis of Th1/Th2 response pattern for erythrodermic psoriasis. Journal Of Huazhong University Of Science And Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban [serial online]. August 2014;34(4):596-601

Is Estrogen bad for you?

Is Estrogen bad for you?

Estrogen, Estrogen…… I need you and I hate you all at the same time!

We talked about the effects of soy as an estrogen like compound on our bodies, but I didn’t really get into the complexity of this hormone.

Did you know that estrogen needs to be detoxified in our body through the same phase 1 pathway as drugs, toxins, and various food substances we ingest?

Our body really only needs a very small amount of estrogen in the body to function and communicate with other hormones. As a result, the body views estrogen as a potentially dangerous toxin and needs to get rid of it, in excess.

Estrogen is metabolized through three reactions.

  1. Liver enzyme, 1A1 which takes Estrogen —> E2 (2-OH)
  2. Liver enzyme, 1B1 which takes Estrogen —>E4 (4-OH)
  3. Liver enzyme, 2C which takes Estrogen —>E16 (16-OH)

This is complex so I’m going to do my best to simplify.

But I needed you to know the root of this so you can understand the rest…..

So let’s put this together.

These three molecules have the same dangerous potential as other phase I detoxification by-products.  They must therefore be rapidly detoxified using a number of phase II pathways. Because of the large number of P450 SNPs (single nucleotide polymorphisms), there is great variation in the human population. The differences in our bodies ability to detoxify in different proportions of 2E, 4E, and 16E have shown to potentially predict risk of different estrogen-related diseases, such as breast cancer.

As we’ve discuss before, different environmental factors have an impact on our liver enzymes and their ability to detoxify.  For example, we recently talked about Brassica vegetables and indol-3-carinol (I3C).  This compound I3C found in these vegetables actually boosts liver enzyme 1A1 to breakdown estrogen to the 2E metabolite.  On a different note, enzyme 1B1 that breaks estrogen to 4E metabolite, can be boosted or slowed down.  Chemicals in cigarette smoke can actually slow this down which would cause higher levels of estrogen in the body.  Ginseng is an herb that has also been showed to slowdown the ability to break down estrogen.  Lastly, the 2C enzyme actually converts to the strongest bi product 16E, and various drugs have an impact on this pathway.

 

So, you guys should understand detox goes through 2 pathways, phase 1 and phase 2.  We have described all the phase 1 metabolites that are formed, 2E, 4E, and 16E – well we still need to get rid of these so they don’t effect our hormones. That‘s done by Phase 2….

There are a lot of toxins that have been identified as “endocrine disrupters” that impact that bodies ability to do this.  I have experienced this on a number of occasions with protein shakes and protein bars! I’ve literally missed a period for 3 months after consuming protein bars daily for a week, wow!

So these toxins, can cause a higher ratios of 4E and 16E to be floating around our body. Why do we care, 4E is DNA damaging and 16E is a stronger metabolite with estrogen properties than estrogen itself.

 

 What kind of toxins… Well let’s start with pesticides

Pesticides were found to significantly increase the ratio of 16E to 2E. Additionally, flame retardants like Tetrabromobisphenol (BFR), act as endocrine disruptors due to estrogen like properties.  Investigators suggest that the ratio of 16E to 2E may provide a marker for analyzing breast cancer risk and for generating preventive nutritional strategies and interventions.

Due to structural similarities to Estradiol (E2), phytoestrogens found in soy bind to E2 receptors and can act as endocrine disruptors and produce adverse health effects (Rietjens et al., 2013)

Some of these enzymes detoxify estrogen at the 2 position, and others act at the 16 position.   There is thought that environment chemicals we ingest change the way our liver communicates with our body resulting in estrogen to be “detoxified” at the 16 position – which is the most harmful form.

This could explain why postmenopausal women with the highest circulating estradiol (E2) levels have the greatest frequency of breast cancer- although this isn’t conclusive.

Remember that very small amounts of estrogen appear to have large effects and that estrogen is viewed by the body as a toxin. 

From what we understand about detoxification in our body, it is important to not only keep our liver healthy so that we can metabolize the excess estrogen initially, but to eat and continue to replenish are necessary cofactors for phase 2 detox with plant based foods!