Autoimmunity and estrogen metabolism

[Gaby]

I've been hearing several talks from the last Autoimmune summit: _http://autoimmunesummit.com/

Many of the topics have been already discussed in this forum, but it was interesting to hear the speculations on why autoimmune diseases are more frequent in women.

They were discussing that certain metabolites (16alpha-hydroxyestrone) were associated with an increased risk of autoimmune diseases, while other metabolites (estriol) were associated with a decreased risk. This is why some women improve during pregnancy, and then relapse afterwards. Estriol is only produced in significant amounts during pregnancy as it is made by the placenta. Anecdotally, a physician shared that she knew of people keeping placentas after their pregnancies to use as supplements :/

Clinicians were reporting how their autoimmune patients improved with estrogen cream (without 16alpha-hydroxyestrone), diindolylmethane (DIM) and indole-3-carbinol (I3C) derived from cruciferous vegetables (which alter estrogen metabolism) , curcumin, primrose oil (very favored for re-balancing hormones) and Omega 3s in generous quantities.

The topic of estrogen and autoimmunity is hardly discussed, but it was interesting to see that clinicians were seeing positive results with their patients. It was also interesting to see that this was something happening in peripheral tissues, i.e. joints as in rheumatoid arthritis but also other autoimmune diseases. So measuring estrogen metabolites in blood was not very clarifying.

They also noted that women who took oral contraceptives were particularly at risk for autoimmune diseases.

More information here:

Estrogen metabolism and autoimmunity
_http://www.ncbi.nlm.nih.gov/pubmed/22155198

Epidemiological and experimental immunological evidence suggest that estrogens enhance the humoral immune response, and at the same time, seem to play important roles in pathophysiology of autoimmune rheumatic diseases. Estrogens in human subjects are generally considered as enhancers of cell proliferation (anti-apoptotic), however, rather than through their serum levels (that may exert opposite dose-related effects), they play important roles through their peripheral metabolites especially in autoimmune rheumatic diseases. Several investigations strongly support an accelerated aromatase-mediated peripheral metabolic conversion of upstream androgen precursors to estrogen metabolites in peripheral tissues affected by immune/inflammatory reactions, both, in male and female patients. In RA synovial tissue, biological effects of these metabolites as a consequence of altered peripheral sex hormone synthesis (intracrine, e.g., at the level of macrophages and fibroblasts) mainly results in stimulation of cell proliferation and cytokine production (i.e. TNF). It was shown that RA synovial cells mainly produce the cell proproliferative 16alpha-hydroxyestrone which, in addition to 16alpha-hydroxy-17beta-estradiol, is the downstream estrogen metabolite that interferes with monocyte proliferation. Therefore, a preponderance of 16alpha-hydroxylated estrogens is an unfavorable sign, at least, in synovial inflammation and possibly related synovial tissue hyperplasia. Interestingly, urinary concentration and total urinary loss of 2-hydroxyestrogens was found 10 times higher in healthy subjects compared to RA or SLE patients irrespective of prior prednisolone treatment or sex. The intracrine synthesis of active estrogen metabolites at the level of cells involved in the immune response (e.g. macrophages and fibroblasts) represents a common pathway that characterizes a similar final immune reactivity in both male and female patients.

Estrogens and autoimmune diseases
_http://www.ncbi.nlm.nih.gov/pubmed/17261796

Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients.

It seems to me that this is one of the reasons why low dose doxycicline therapy is so useful in rheumatoid arthritis, it helps to decrease the production of inflammatory cytokines in peripheral tissue.

Minus the estrogen cream, all suggested supplements are very easy to get and safe to try as they only add benefits.

FWIW!

 

[Mrs.Tigersoap]

Anecdotally, a physician shared that she knew of people keeping placentas after their pregnancies to use as supplements :/

Yes, I remember that 'trend' now that you mention it!
I remember reading articles about how it was all the rage in some 'eco' circles to keep the placenta, cook it and eat it.
I'm really uneasy about eating something a human body (mine, someone else's) produced but that's just me. :)

They also noted that women who took oral contraceptives were particularly at risk for autoimmune diseases.

When you see the number of women taking oral contraceptives nowadays, that's really concerning.

 

[Gaby]

When you see the number of women taking oral contraceptives nowadays, that's really concerning.

It is a global disaster!

The Autoimmune Summit interview to Jeffrey Bland, author of "The disease delusion" and founding father of functional medicine, was most interesting.

He talks about the pathophysiology of autoimmune diseases. A high carb diet has a key role by "caramelizing" proteins in the blood and tissues. For instance, sugar binds to albumin to form glycoalbumin which then the body recognizes as foreign. Then, a person becomes more and more intolerant to a modification of ourselves, to substances that are building up in the body. In this case we become "glycated" and have an increased risk of autoimmune disease and when there is a genetic susceptibility that makes the immune system react to foreign objects, then we become hypersensitive.

Despite the well documented genetic role in autoimmune diseases, he explains that the environment is the major key because it is the one that creates the injury to the host tissue. There is no such thing as a monogenetic autoimmune disease since several genes are always involved. There are people nowadays diagnosed with celiac disease who don't carry the well known genes for this disease. Genetics in autoimmune diseases are very complex and by themselves, they don't cause disease. The cause can be found in environmental factors which then trigger these genes.

He does admit that immuno-suppressive therapy works incredibly well because it uncouples the immune system effectively... All at the cost of their toxic side effects.

Linking environment and genes, he then speaks about epigenetics which are a powerful part of the story. As covered in sott and discussed in this forum, diet lifestyle and chemical exposure during pregnancy and so forth have an effect in children. So perhaps parents did better, but future generations are at an increased risk for autoimmune disease as the DNA damage adds up from an increasing toxic environment.

The consequences of epigenetic changes produce marks of injury on DNA which according to clinical experience, can be modified. So that is good news!

He covers in his book the most important factors that create DNA damage, among some of them:

Polyphenolic molecules: phenol, an industrial solvent. It has a special ability to injure DNA.
Gluten which produces what he calls "epigenetic secondary marks". Intolerance to gluten manifests as systemic inflammation and autoimmunity.
Heavy metals with a special mention to lead, cadmium, mercury. He shares how some people with multiple sclerosis go into remission when they have their mercury amalgalms removed.
Arsenic which is a toxic mineral.
Malnutrition: insufficiency of B12, B6 in people who cannot methylate. Vitamin D deficiency.
Radiation.
Aldehydes
Chronic infections, with a special mention to sinus problems, gut and mouth infections (periodontitis, etc). Chronic infections injure the tissues, so then the immune system overreacts.
Stress

I liked the way he describes mainstream medicine. He refers to the "Diagnostitian" - you know more and more about less and less until you know nothing.

"You can name the tree and know nothing about the forest. Maybe it is better to be an ecologist and know the forest and then you can figure out the trees later."

Due to therapy side effects and disease course, autoimmune diseases often have these comorbids: osteoporosis and heart disease. So patients are often seeing a rheumatologist or immunologist, orthopedist or endocrinologist for osteoporosis, etc. They can have 3 diseases with 3 sets of drugs given by 3 doctors, at the very best. Then, the toxicity adds up.

He emphasizes the need to do some sort of exercise since body structure is tied closely together with function. And finally, he talks about the Omega 3 controversy. Some say Omega 3s are dangerous, but he emphasizes that considering the bulk of the research, there are definite pros for omega 3s. Rheumatoid arthritis has been reversed with Omega 3s and so forth.

Much of what he mentioned has already been discussed in the forum, it is just interesting how neatly he describes it from a pathophysiological point of view.