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Female Hormones and Autoimmune Disease - the Connection

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This article originally appeared in the Winter 2011 edition of's Journal of Gluten-Sensitivity. 05/16/2011 - Nearly 75% of the 24 million Americans suffering from autoimmune disease are women, according to the American Autoimmune Related Diseases Association (AARDA).  Women appear to mount larger inflammatory responses than men when their immune systems are triggered, thereby increasing their risk of autoimmunity.  The fact that sex hormones are involved is indicated by the fact that many autoimmune diseases fluctuate with hormonal changes such as those that occur during pregnancy, during the menstrual cycle, or when using oral contraceptives. A history of pregnancy also appears to increase the risk for autoimmune disease.

The sex hormone that is commonly low in such women is Dehydroepiandrosterone (DHEA). This is a natural steroid and is produced by the adrenal glands, the reproductive organs and the brain.  DHEA is used by the body to make the male and female hormones, testosterone and estrogen respectively, and is known to have anti-inflammatory effects. It has been proposed that a DHEA deficiency is a contributing factor in autoimmune diseases.  Last year a study was done to look at precisely that effect.  The study’s conclusions have been supported by other, similar research and I think you’ll find it quite interesting.
The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 6 2044-2051(2009) published an article entitled “Low Serum Levels of Sex Steroids Are Associated with Disease Characteristics in Primary Sjogren’s Syndrome; Supplementation with Dehydroepiandrosterone Restores the Concentrations”. The authors investigated whether there was a relationship between steroid levels and the disease characteristics of Sjogren’s.

They based their study on the known data that DHEA not only declines with aging but is reduced in Sjogren’s, an autoimmune disease. The study was populated by 23 post-menopausal women with primary Sjogren’s syndrome and subnormal levels of DHEA. The investigation was a controlled, double blind crossover study, conducted over a 9 month period, where DHEA was assessed by sophisticated laboratory measurements and typical symptoms of Sjogren’s such as dry mouth and eyes and salivary flow rates were similarly assessed.

Results revealed a strong correlation between low DHEA and Sjogren’s symptoms.  DHEA and its sex hormone metabolites (testosterone and estrogen) were found to increase with DHEA supplementation but not with the placebo. Symptoms such as dry eyes were seen to improve as estrogen levels

The researchers concluded that the disease manifestations of primary Sjogren’s syndrome were associated with low sex hormone levels and the supplementation of DHEA allowed the body to transform into androgens, testosterone and estrogen, with testosterone production predominating.

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Please allow me to add some personal interpretation. For the most part I agree with the premise and applaud the results. The facts that autoimmune disease occurs more often in women, that women frequently have low DHEA, and that androgens have anti-inflammatory effects that can benefit autoimmune disease are all true.

But should we simply give such women DHEA and call it a day? I don’t think so.  I propose that we do three things: First, evaluate hormonal levels in women regularly; Second, address WHY their hormonal levels are imbalanced;  And third, when supplementing with hormones such as DHEA, ensure that the delivery system is one that mimics what the body does naturally.

Remember that autoimmune disease can begin many years before the first symptoms become manifest. Therefore evaluating hormonal levels in our younger women is a good idea.  When I find DHEA levels that are low, my first order of business is to assess why.  Frequently it is due to a phenomenon known as “pregnenelone steal” that occurs when the adrenal glands are under stress.  It is a common occurrence and one of the fantastic abilities of the human body to shift from one pathway to another when under stress.  The “steal” pathway diverts the body away from making sex hormones and instead it makes more “stress” hormones.  So while adding some DHEA into the mix might very well help, does it make sense to find out WHY it’s being diverted away from making sex hormones?  I hope so because it’s the very foundation of the medicine that we practice—functional medicine.

Once you understand the root cause of the deficiency you can take steps to truly remedy it rather than simply covering it up by taking DHEA.  Not to keep hitting you over the head with this concept, but supplementing with DHEA as your sole treatment misses the underlying cause since the body is designed to make adequate quantities of DHEA.

A common reason for the diversion or “steal” pathway to become activated is adrenal stress from poor absorption of nutrients, unstable blood sugar and the presence of infections—all problems we see with the gluten intolerant patient! While I’m not implying that every autoimmune patient has a gluten intolerance, it certainly warrants screening all of them because of its high prevalence.
As we travel down the road to optimal health through avoiding any food the body isn’t tolerating well, improving the integrity of the small intestine and normalizing adrenal function, there are certainly times when hormonal supplementation is beneficial. I don’t recommend the oral route because the first place the hormone travels is to the liver and this can be burdensome to that organ.  When the body makes hormones naturally it delivers them straight to the bloodstream.  In an effort to mimic that delivery system we use a buccal route (placed between cheek and gum in the mouth) that does a good job in bringing the hormone directly to the bloodstream and bypassing the liver and digestive tract.

Autoimmune diseases comprise the third leading cause of death in our country and research strongly suggests that its rapid increase is due to environmental factors, especially those that weaken the small intestine. I am committed to earlier diagnosis while the disease is still remediable, as well as overall reduction of incidence through addressing digestive health.

I hope you find this informative.  Please share this information with those who have autoimmune disease themselves as well as in their family. welcomes your comments below (registration is NOT required).

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10 Responses:

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said this on
23 May 2011 9:44:24 AM PST
Thanks for sharing your findings. It would also be helpful for us to have a choice of supplements name brands and specifics from which to choose or ask our doctor or pharmacy to order.
Also, I have found corn cause a lingering inflammatory problem or more so quietly filters an inflammatory response throughout my whole body system. A build of corn in my system leads to skin welts or sensitivity to detergents and an overall inflammation leading even to bladder and kidney problems. It is just much quieter than gluten. Removing corn is difficult as it is in 97% of all grocery store items . But the removal of corn allows my body a rest and a chance to be normal. I understand a clinical study found this corn problem in 50% of celiacs so I imagine it is quietly destructive to may people. What can be done to make this more well known, listed as an allergen, researched as a possible culprit for many diseases?

Gloria Brown
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said this on
23 May 2011 11:33:00 AM PST
Indeed, why hormonal (and other levels) are imbalanced is critical and may instead indicate ever-prevalent gluten offsetting Celiac metabolisms. Experiencing Sjogrens for me signals gluten has found it's way into my system. Once the source of gluten exposure is eliminated, so is Sjogrens. Ingesting DHEA, which may contain trace gluten excipients, could dangerously camouflage the true source of the problem. People with silent CD are especially at risk.

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said this on
18 Aug 2011 3:11:17 PM PST
Is corn also related to setting off gluten symptoms? Also who would you go to on finding out your hormonal or adrenal insufficiency that may be adding to celiac problems and Sjogrens syndrome--I have both as well as fibromyalgia, osteopenia, cysts on ovaries, left sided pain when eating, right lower quad pain most recent symptom, as well as edema, fatigue, all over body & joint pains, cysts on the base of spine, memory loss, upper and lower extremity tremors, tingling, numbness, and another new symptom of left breast itching, and bilateral severe breast pain, spinal pain, hip pains, go from diarrhea to constipation & back again, fevers, cold intolerance, fatigue, malaise, migraines. rashes that itch terribly, unexplained edema that diuretics do not help, occasional blisters on feet when take hot bath and on fingers. Huge amt of stress, constand nausea, some vomiting, appetite loss, hypoglycemia, man that's all I can thing of right now but I know there's more. Can the hormonal imbalance effect all this as well as the celiac or is the celiac my major problem here?

jennifer uhlman
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said this on
12 Apr 2015 10:22:21 PM PST
Wow you poor thing. I have so many of your symptoms I'm scared... I'm treating with Enbrel for the arthritis and Nurontin for fibromyalgia, and Ultram for stenosis of the spinal canal. Also pre-menopausal. My hormones are killing me. I think celiac is the culprit but now I've been gluten-free for 4 years and I still have so much pain I don't know what to do. What do people like us do? When you go to a new doctor they look at you like you are crazy with all this stuff. And you know it's happening but it sounds crazy. I feel like I'm losing my mind some days.

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said this on
25 Oct 2015 6:27:38 AM PST
You might have Tarlov Cyst Disease affecting nerves which affect many things. I have them on nerve endings in lumbar and sacral area and doing consult on Wednesday and hope surgery is soon as I am on my back most of the time. Praying for you!


said this on
27 Jun 2014 8:01:37 PM PST
I have just been diagnosed with sjogrens, and had a hysterectomy very young. I am reading your article and wonder if you can please tell me more on sjogrens and gluten , I have not heard this.

I would appreciate any help you may produce. I was also wondering if hormones do play a role in it, since women are usually the ones who get the disease.
Thank you for any information you may provide.

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said this on
23 May 2011 12:14:52 PM PST
I wonder if this deficiency could be caused by long-term birth-control pill usage, i.e., you replace your naturally produced estrogen and progesterone with synthetics, and it's no wonder they can't go back to normal after discontinuing the pill? The pill is also associated with decreased libido, even permanently after the pill is discontinued, which makes me wonder if it does permanent damage to the androgen hormone production in women (required for libido).

carol stratton
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said this on
25 May 2011 10:14:57 AM PST
Quite enlightening & a PhD with writing personality

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said this on
17 Aug 2014 11:16:57 PM PST
Very helpful article. My labs came back that my DHEA is less than .01 - and I'm only 32. Doctor is testing me for antibodies to see if I may have an autoimmune disease; I suffer from dry eyes, mouth, and diminished libido. Am in otherwise great health, but am concerned that I may have Sjogrens. Have started a 6-8 week long autoimmune diet protocol.

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said this on
21 Sep 2016 4:57:03 PM PST
I have Hashimoto's thyroidism, Sjogren syndrome, Raynaud, SLE and RA. It's very difficult having all of this happening to me simultaneously and even attempt to get intimate. Sex is beautiful and I like it - it just hurts afterward (whole body pain)... I'm unsure what to do here.

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