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Infertility and Autoimmune Hypothyroid (Hashimoto's Thyroiditis)

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Infertility and Autoimmune Hypothyroid (Hashimoto's Thyroiditis) Infertility and Autoimmune Hypothyroid (Hashimoto’s Thyroiditis): Neuroendocrine-Immune modulation 1 and fertility support utilizing Traditional Herbal Medicine (THM). Infertility and Autoimmune Hypothyroid (Hashimoto’s Thyroiditis): Neuroendocrine-Immune modulation and fertility support utilizing Traditional Herbal Medicine (THM). A Systematic Review By Gina Mortellaro-Gomez, M.S.O.M., NCCAOM Dipl. O.M., L.Ac, FABORM A capstone project Presented in partial fulfillment of the requirements for the Doctor of Acupuncture and Oriental Medicine Degree Yo San University Los Angeles, California March 2015 Infertility and Autoimmune Hypothyroid (Hashimoto’s Thyroiditis): Neuroendocrine-Immune modulation 2 and fertility support utilizing Traditional Herbal Medicine (THM). Approval Signatures Page This Capstone Project has been reviewed and approved by: __________________________________________________________ 2/18/2015__ Eric Tamrazian, MD, Capstone Project Advisor Date _____________________________________________________________2/18/2015____ Daoshing Ni, L. Ac., Specialty Chair Date ____________________________________________________________ 2/18/2015_ Andrea Murchison, DAOM, L. Ac., Program Director Date Infertility and Autoimmune Hypothyroid (Hashimoto’s Thyroiditis): Neuroendocrine-Immune modulation 3 and fertility support utilizing Traditional Herbal Medicine (THM). Acknowledgements To my advisor Dr. Tamrazian, who was my North Star in this Capstone Thesis process. Thank you for your compassionate and brilliant guidance, insight and wisdom and for continually inspiring those around you in “in all things medicine”. I would also like to thank Yo San University for giving me the opportunity to further my learning process within the fields of Chinese and integrative medicine and for providing such a dynamic, challenging and friendly learning environment filled with some of the most brilliant professors and instructors I have ever encountered. Yo San will live on in my heart forever. And last but not least, I would like to dedicate this Capstone thesis to my husband, Gary. Thank you for your unwavering love, support, understanding and belief in my medical studies and journey. You are my inspiration for it all and I love you with all my heart! Infertility and Autoimmune Hypothyroid (Hashimoto’s Thyroiditis): Neuroendocrine-Immune modulation 4 and fertility support utilizing Traditional Herbal Medicine (THM). Abstract This retrospective systematic review investigated “Traditional Herbal Medicine” (THM) in the form of single herbal extracts, traditional herbal formulas, as well as, isolated chemical and biologic compounds found in the individual herbs, as an alternative and or complimentary treatment option in modulating the neuro-endocrine immune axis, normalizing thyroid and reproductive hormones and dampening pro-inflammatory cytokine and anti-body production in fertility patients with Hashimoto’s thyroiditis, thereby improving clinical outcomes. The primary question associated with this research capstone was: “How might Traditional Herbal Medicine (THM), modulate the Neuroendocrine-Immune Axis and enhance fertility potential in women diagnosed with Autoimmune Hypothyroid (Hashimoto’s Thyroiditis)?” After a thorough review and analysis of the studies, our hypothesis was confirmed in that THM shows a potentially significant improvement in outcomes for patients with Hashimoto’s Thyroiditis also dealing with infertility by significantly influencing the neuroendocrine- immune axis as evidenced in this systematic review. Infertility and Autoimmune Hypothyroid (Hashimoto’s Thyroiditis): Neuroendocrine-Immune modulation 5 and fertility support utilizing Traditional Herbal Medicine (THM). Table of Contents Chapter 1: Introduction ........................................................................................................................................6 Chapter 2: Literature Review .............................................................................................................................32 Chapter 3: Methods .............................................................................................................................................83 Chapter 4: Results................................................................................................................................................87 Chapter 5: Discussion ..........................................................................................................................................98 References ...........................................................................................................................................................117 Appendices ..........................................................................................................................................................135 Abstraction Tables 1A-1E Abstraction Tables 2A-2E Tables 36-40 (Single herbs and herbal formulas investigated) Copy of IRB Approval Letter Infertility and Autoimmune Hypothyroid (Hashimoto’s Thyroiditis): Neuroendocrine-Immune modulation 6 and fertility support utilizing Traditional Herbal Medicine (THM). Chapter 1: Introduction What is Hashimoto’s Thyroiditis? Hashimoto’s Thyroiditis (HT) is a chronic, inflammatory, autoimmune disease of the thyroid gland named after its’ discoverer, Hakaru Hashimoto, a Japanese physician who worked in Berlin, Germany before World War I (Stephanie L Lee, MD, 2014). HT is also referred to as “Chronic Thyroiditis” and is one type of hypothyroidism. HT is characterized by the destruction of thyroid follicular cells by various cell and anti-body mediated immune processes and is regarded as a polygenic disorder resulting from the combination of a genetic predisposition in conjunction with an environmental trigger (Fountoulakis & Tsatsoulis, 2004). HT occurs with increased prevalence in a variety of other type 1 and type 2 autoimmune polyglandular syndromes, such as pernicious anemia, celiac disease, adrenal insufficiency (Addison’s disease), myasthenia gravis, premature ovarian failure, rheumatoid arthritis, systemic lupus erythematosus, sjogren’s syndrome and type 1 diabetes mellitus, (Wiebolt et al., 2011; Vestgaard, Nielsen, Rasmussen, Damm, & Mathiesen, 2008), as well as occurring in a variety of other disorders related to a sharing of genetic and environmental factors (Weetman, 2011). According to the American Autoimmune Related Diseases Association, Inc., approximately 50 million Americans (one in five people) suffer from autoimmune diseases. Thyroid autoimmune diseases are the most common of autoimmune disorders, affecting 7-8 percent of the U.S. Population (Betterle & Zanchetta, 2003). Worldwide, the most common cause of hypothyroidism is iodine deficiency, however in the United States, and in areas where iodine intake is adequate, HT is the most common cause of spontaneous hypothyroidism (Stephanie L Lee, MD, 2014; Braverman & Cooper, 2012). The incidence rate of HT is estimated to be 10-15 times higher in females than in males with the most commonly affected age range being 30-50 years of age (Stephanie L Lee, MD, 2014; Braverman & Cooper, 2012). In autoimmune diseases, it is the regulatory T cells that begin to behave erratically signaling the body to produce excess T helper cells or deficient T suppressor cells that ultimately leads to destruction of bodily tissue Infertility and Autoimmune Hypothyroid (Hashimoto’s Thyroiditis): Neuroendocrine-Immune modulation 7 and fertility support utilizing Traditional Herbal Medicine (THM). (Fountoulakis & Tsatsoulis, 2004)(Kharrazian, 2010). The T-helper cells secreting cytokines that direct immune cells to attack target cells potentially infected or recognized as abnormal, are known as TH-1 cells and are associated with the “TH-1 pro-inflammatory/T-cell mediated pathway” of the immune system. The cytokines associated with the TH-1 pathway are: IL-2 (Interleukin 2), IL-12, Tumor Necrosis Factor alpha (TNFa), and Interferon gamma (IFN-g) (Braverman & Cooper, 2012). The TH-1 immune cells are responsible for an immediate immune response to an active Antigen (organic compounds such as: food, mold, bacteria, chronic virus, or parasite) and or Hapten (Inorganic compounds such as: environmental chemicals or heavy metals). TH-2 cells, associated with the “TH-2 pathway” of the immune system (anti-inflammatory, B-cell mediated), which stimulate immune B cells in charge of tagging the antigen/hapten complex for later destruction by natural killer and cytotoxic T Cells, secrete a variety of cytokines that tend to oppose the cytokines secreted by TH-1 cells. The cytokines associated with the TH-2 pathway are: IL-4, IL-5, IL-6, IL-10, and IL-13 (Braverman & Cooper, 2012). Further research has also identified TH-3 and TH-17 subsets of the immune system (Kharrazian 2013). TH-3 subsets are related to regulatory T-cell function (CD25+4). Regulatory T-cells are used to modulate the balance of TH-1 and TH-2 responses. TH-3 is promoted by TGF-B (Transforming growth factor beta), a protein that controls cellular proliferation and differentiation. TH-17 is T- cell activity related to the immunological destructiveness potential of TH-1 and TH-2 shifts. The greater the TH-17 activity, the greater potential for immunological destruction is present. TH-17 activity is promoted primarily by IL-6 and TH-17 is measured by IL-17. HT is an organ-specific autoimmune disease considered to be the result of an immune response against the thyroid leading to
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