Managing Multiple Disorders in One Body

Managing Multiple Disorders in One Body

Women with PCOS exhibit a very high degree of medical complexity, including dysfunctions of key metabolic and immune mechanisms, affecting a wide range of organ systems. Such dysfunctions can manifest as multiple disorders in one body! Identifying the root causes and common conditions that weave their way through these multiple disorders will facilitate finding a unifying remedy, and eventually a cure, for PCOS and its related conditions.

By understanding how foundational dysfunctions develop and then lead to a myriad of manifestations, we can take those crucial first steps. Conditions found at higher rates in PCOS women than in the general population includeautoimmune thyroid disease (Hashimoto’s Thyroiditis), endometriosis, uterine fibroids (leiomyomata), adenomyosis (uterine lining glands within the muscle of the uterus), and several cancers.

Are women with PCOS simply unlucky to have so many medical maladies in one body, or is there a common theme to explain this? Once you delve beneath the surface, you come to recognize that all of these conditions have similar underlying mechanisms. Uniting all of them are the following: an abnormally functioning immune system, marked by chronic inflammation with elevations of inflammatory signaling agents called inflammatory cytokines, early age exposures to environmental toxicants (chemical endocrine disruptors), nutritional deficiencies, and gut microbiome abnormalities (dysbiosis). The ultimate unifying and underlying cause for all of these maladies in PCOS women is a foundational hormonalproblem: a major dysfunction of estrogen and its receptors, including its production and metabolic degradation. Estrogen is the master hormone, essential for metabolic health,and this requires a properly regulated immune system.  Sadly, PCOS women do not have proper metabolic or immune health.

Let’s begin with a quick overview of the conditions mentioned above. Endometriosis involves a severe localized inflammation in the pelvis, with high levels of inflammatory cytokines within the intra-abdominal (peritoneal) fluid. Interestingly, most menstruating women have some uterine contents flow backwards with each menses, with fluids and tissue passing through and out the Fallopian Tubes. The body’s immune system normally dissolves and gobbles up that tissue, but in women with endometriosis, this process malfunctions, and little holes in the lining of the pelvis (the peritoneum) are created, allowing living cells from the uterine lining to implant and thrive.

This process is controlled by a system of enzymes, called Matrix Metalloproteinases (which remodel tissue) along with immune cells of the body. These cells and processes are under the control of estrogen, which in PCOS women is not functioning correctly. One type of theseimmune cells – the Mast Cell, which isalso controlled by estrogen – accumulates within the pelvis of women with endometriosis, releasingmassive quantities of inflammatory cytokines and chemokines (signaling agents which call other inflammatory white blood cells to the scene.) Thiscreates and sustainslocalized inflammation, promotinglocal estrogen production, and further stimulating growth of the ectopic endometrial cells.

In the case of uterine fibroids, malfunctioning Matrix Metalloproteinases and abnormal local production of estrogen and progesterone cause the muscle cells of the uterus to grow abnormally, creating muscle tumors – fibroids (leiomyomata). Likewise, adenomyosis involves the dysfunction of both the Matrix Metalloproteinases and of estrogen, resulting in the invasion of the endometrial (lining) cells into the muscle of the uterus.

Hashimoto’s Thyroiditis, an autoimmune disease, also involves dysfunction of the immune system, gut dysbiosis,and impaired gut permeability (leaky gut), all related to abnormal estrogen function. Lastly, cancer, the ultimate immune dysfunction, involves uncontrolled inflammation and estrogen malfunction or deficiency. Not surprisingly, the incidence of many cancers is substantially higher in women with estrogen dysfunctions – PCOS, adenomyosis, fibroids, and endometriosis – compared with the rest of the female population.

And what connects PCOS with those other conditions? What is the root cause of PCOS? We now understand that it involves chronic inflammation, gut dysbiosis, and leaky gut;and that estrogen malfunction is at the root of those problems. The cause for this estrogen malfunction involves exposures to endocrine disrupting chemicals at critical points of development – in utero, during infancy, and at puberty, in genetically susceptible women. This inflammatory state is exacerbated by continued chemical exposures and the consumption of a high fat/high sugar diet, filled with processed foods.

Despite all of this, there is substantial reason for hope. A fiber rich diet, stress control, exercise, timed eating and periodic fasting, along with the judicious use of bioidentical hormones, can ameliorate these problems. More on my PCOS protocols for health will be forthcoming in future articles.

Nielsen NM et al. Hum Reprod. 2011;26(6):1555-9
Smarr MM et al. FertilSteril. 2016 Jul 15. Soo15-0282(16)61389-4
Khoufache et al. Minerva Endocrinol. 2012;37(1):75-92
Burney et al. Fert and Steril, 2012;98(3):511-19
Konno et al. Human Cell. 2003;16(3):144-49
Cuevas et al. Reprod Sci.2012;19(8):851-62
Theoharides.ExpDermatol. 2017
Nat Rev Immunol. 2010
Hart, David. 2015. Intern J of Inflam. 2012;452095
Urb et al. PLOS Pathog. 2012;8(4)
Abraham et al. Nat Rev Immunol. 2010;10(6):440-52
Menzies et al. Hum Reprod Update. 2011;17:383-96
Binda et al. ExpOpin on Ther Targets. 2017;21(1)67-75
Vliagoftis et al. Immunol Rev. 2005; 206:190-203
Qiao et al. Blood. 2006;107:610-18
Plos Pathog.2012;8(4):e1002619
Alvarez et al. Neuroscience. 2014;258:111-120
Hart, David. 2015. Intern J of Inflam. 2012;452095
Bulun et al. SmeRepr Med 2004;22(1):45
Sharpe-Timms et al. Ann NY Acad Sci.2002;955:147-56
Smarr MM et al. FertilSteril. 2016 Jul 15. Soo15-0282(16)61389-4
Bayoglu et al. Eur J Ob GynReprod Biol. 2015;184:1-6
Ozcan et al. GyncolEndocrinol. 2015;31(3):219-24
Yavuzetal.J Cancer Res Ther. 2014;10(2):324-9
Cao et al. Evid Based Complement Alternat Med. 2014;781684
Wang et al. Angiogenesis. 2013;16(1):59-69
Ricci et al. Hum Reprod. 2013;28(1):178-88
Xu et al. FertilSteril. 2011;96(4);1021-8
Jackson et al. Hum Reprod. 2005;20:2014-20
Halpam et al. Rev Assoc Med Bras 2015;61(6)519-23
Agostinis et al. Mediators Inflamm. 2015; 918089
Mojzis J et al. Pharmacol Res 2008. 57(4):259-65
Maia et al. Int J of Women’s Health;2012;4:61-65
Kim KA et al. PLOS one. 2012;7(10):47713
Heard ME et al. Endocrinology. 2016 Jul;157(7):2870-82