Articles

Linking Estrogen Deficiency to Autoimmune Diseases like MS, RA, SLE, and IBD

By Janna Gordon, RPh.

Autoimmune disorders are diseases in which the body's own immune system develops antibodies for, and attacks self tissue. This may often lead to dysfunction, and eventual loss of function of the targeted tissues and organ systems. Most autoimmune disorders are influenced by environmental conditions, but many still have a significant genetic relation. No single genetic defect has yet been established for autoimmune disorders, including: rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and diabetes type 1. These disorders are considered "polygenic" or to be determined by more than one gene.

It is understood that the estrogens have some effect in modulating or affecting change in autoimmune diseases. This link has been especially strong with estradiol, but other estrogens as well. Estrogen almost certainly plays a role in influencing autoimmune diseases such as MS. This is suspected to be the case in other autoimmune disorders too: as seen in patients with RA and SLE. It is proposed that not only estradiol has interactions with the immune system, but also estradiol precursor hormones and intermediate metabolites, such as DHEA, may play a role. Due to the sheer volume of hormones and interleukins and related metabolites involved with the immune cascade, it is often difficult to see the effect that one hormone has.

The association between estrogens and the immune system may be linked back to pregnancy. Changes in the immune system are necessary during pregnancy to prevent rejection of the fetus. Estrogen also has a key role in various physiological systems of the body besides reproduction. This has been proposed to be the reason behind the bias seen between men and women for different immunological disorders.

Many inflammatory diseases, such as RA and MS are ameliorated or improve during pregnancy but worsen after childbirth[1,2]. Pregnancy appears to have a significant protective effect on women with MS. The number of MS attacks or relapses is reduced during pregnancy, especially in the second and third trimesters. It is proposed that this effect is due to the increased estriol levels caused by pregnancy. Estriol is a protective estrogen with weak estrogenic properties. It binds to estrogen receptor sites to prevent estradiol binding. The PRIMS study[3] suggests that treatment with Estriol in a dosage of approximately 8mg/day, about the same as that seen in the 3rd trimester of pregnancy, is protective of MS. Estriol given to nonpregnant women with relapsing-remitting MS showed increased protective immune responses, decreased number and volume of lesions seen on monthly cerebral MRIs, and fewer number of relapses[3].

Systemic lupus erythematosus has been reported to be either unaffected by pregnancy[4] or aggravated[5]. While both RA and MS are impacted by the immune system in different ways, pregnancy also seems to affect these disorders differently.

It seems that it is estrogen, not progesterone that may confer protection against RA. The flare-up of arthritis after childbirth is believed to be caused by the increased levels in prolactin due to lactation. Disease outbreak after birth may be prevented by estradiol administered immediately after birth. Since estrogen levels drop just prior to birth, there is increased chance for a prolactin stimulated immune response, due to estrogen no longer being available in sufficient quantities to suppress this reaction.

Fluctuations in disease symptoms in RA, MS and SLE are reported to correlate with the menstrual cycle. In RA, several studies on estrogen replacement therapy have shown an improvement in the disease in postmenopausal women[7,8]. Men with RA typically show low testosterone levels. This link suggests that testosterone plays a role. Indeed, testosterone replacement has been implicated to have beneficial effects[9]. Testosterone is regarded as an immunosuppressive hormone and a lack of testosterone produces a loss of protection against development of RA.

Estrogen is noted to have many varying effects on immune cells. Treatment has been shown to impact development and differentiation of some immune cells and suppress immune functions of others[10, 11, 12].

Experimental evidence shows that estrogen may possess strong anti-inflammatory properties. Kane, et.al.[13] put this to test. In their study of 65 menopausal women with inflammatory bowel disease (IBD), it was found that HRT caused significantly less disease flares. The effect seen strengthened when the women took HRT for at least one year.

Fibromyalgia is another autoimmune disease that may be hormonally modulated. A search of the data linking fibromyalgia to estrogen levels showed that there is no link[14,15]. This was conclusively found in two large randomized controlled trials, implying that the data for this is robust. The trials do however prove that fibromyalgia is associated with lower levels of cortisol.

Maintaining estradiol and other hormones within a normal therapeutic range may improve the course of many coexisting conditions in addition to providing relief of menopausal symptoms. Bellevue Pharmacy Solutions has a staff of consultant pharmacists ready to assist you and your physician with managing your compounded bioidentical hormones replacement.

References:

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