The Role of Polycystic Ovarian Syndrome in Chronic Inflammation, Psychological Health, and the Gut Microbiota State: A Case Report

Davis CC; Popp JK

Case Report

J Fam Med. 2022; 9(1): 1285.

The Role of Polycystic Ovarian Syndrome in Chronic Inflammation, Psychological Health, and the Gut Microbiota State: A Case Report

Davis CC and Popp JK*

Athletic Training Program, Purdue University, USA

*Corresponding author: Jennifer K Popp, Athletic Training Program, Purdue University, 800 West Stadium Avenue, West Lafayette, IN 47907, USA

Received: December 18, 2021; Accepted: January 13, 2022; Published: January 20, 2022

Abstract

Polycystic Ovarian Syndrome (PCOS) is endocrine and gynecological disorder that affects women of reproductive age. This is a case report of a patient with PCOS who was misdiagnosed and presented with several endocrine and gynecological symptoms. This case emphasizes the need for a holistic healthcare approach to treat the underlying organ dysfunction in women with PCOS. It highlights the interconnectedness between endocrine and reproductive dysfunction. This case report examines the chronic inflammatory state, risk of developing psychological disorders, and gut microbiota diversity in women with PCOS.

Keywords: Polycystic Ovarian Syndrome; Endocrinology; Gynecology; Psychology; Primary Care

Abbreviations

CBT: Cognitive-Behavioral Therapy; CNS: Central Nervous System; CRP: C-reactive Protein; GI: Gastrointestinal; GM: Gut Microbiota; HPA Axis: Hypothalamus-Pituitary-Adrenal Axis; IR: Insulin Resistance; PCOS: Polycystic Ovarian Syndrome

Case Presentation

Patient is a 22-year-old female who was diagnosed with polycystic ovarian syndrome (PCOS) at 14 years of age. At the age of 13, the patient experienced menarche, followed by amenorrhea for 6 months. During this period of amenorrhea, she presented with unexplained extreme fatigue, headaches, muscular weakness, decreased immunity, and concentration impairment, and was diagnosed with mononucleosis. However, her symptoms lasted 9 months, rather than 2-4 weeks, which is typical with a mononucleosis diagnosis. During these 9 months, the patient was evaluated by many specialists, and underwent a battery of diagnostic tests. At the age of 14, the patient resumed menses; however, the resumption of menses brought the following symptoms: abnormal menstrual cycles, mood swings, cystic acne, anxiety, sharp pelvic pain, abdominal weight gain, and gastrointestinal dysfunction. An internal medicine physician diagnosed the patient with PCOS at the age of 14 years based on chronic fatigue and results of blood work, which revealed the following: elevated insulin levels, decreased thyroid stimulating hormone, and elevated estrogen and androgen levels, along with nutritional deficiencies that included decreased magnesium, and vitamins B12 and D levels. A transvaginal ultrasound performed at age of 20 resulted in additional diagnoses of cystic ovaries and endometriosis.

Immediately following her PCOS diagnosis, the patient began a holistic lifestyle change consisting of healthy foods, regulation of macromolecule input, exercise regimen conducive with her hormonal levels, vitamin supplementation, and stress management techniques. After three months of these lifestyle changes, the patient experienced a significantly improved quality of life. Continued interventions include a complete blood count and comprehensive metabolic panel 2-3 times per year to ensure the interventions are appropriate. The patient is able to function normally; however, her symptoms are cyclical based on menstrual cycle. During periods of stress, the patient becomes fatigued, and struggles to maintain normal insulin levels, which causes an increase in inflammatory markers, leading to gastrointestinal upset and nutrient malabsorption.

Discussion

PCOS is a multifaceted endocrine and gynecological disorder which effects 15-20% of women of reproductive age [1]. This disorder effects every part of the endocrine system [3-13]. The diversity of PCOS symptoms leads to prolonged diagnosis and misguided treatment plans [2]. Diagnosis of PCOS is made by utilizing the Rotterdam Diagnostic Criteria, presented in Table 1 [2]. Symptoms occur as a result of endocrine organs (Table 2) and body systems (Table 3) affected by PCOS [3-13].

Table 1: Rotterdam Diagnostic Criteria 2003 for diagnosing women with polycystic ovarian syndrome [2].




  
    Hyperandrogenism
    Anovulation/Oligo-ovulation
    Polycystic    ovaries via transvaginal ultrasound 
  
  
    Hirsutism 
    Bleeding Interval <21 days 
    Presence of 12 or    more follicles 2-9mm in diameter in either ovary AND/OR
  
  
    Cystic hormonal acne 
    Bleeding Interval    >35 days <8 menses per year
    Increased ovarian    volume > 10mL (without cyst or dominant follicle in either ovary)
  
  
    Male-pattern alopecia 
    Infertility

      No menstruation for    3 consecutive months in last 12 months



Table 1: Rotterdam Diagnostic Criteria 2003 for diagnosing women with polycystic ovarian syndrome [2].

Table 2: Endocrine organs affected by polycystic ovarian syndrome [3-6].




  
    Endocrine Organs
    Pancreas [3,4] 
    Liver [3] 
    Adrenal glands [5] 
    Thyroid gland [6] 
  
  
    Symptoms/Side Effects 
    
      Insulin resistance
      Excess insulin production: abnormal production of androgens by    ovaries and adrenals
      Hypoglycemia
      Increased risk of type 2 diabetes/metabolic disorder
      Central obesity
      Chronic inflammation
    
    
      Elevated blood lipid levels
      Risk of cardiovascular disorders
      Increased demand on liver
      Elevated estrogen levels: need to be detoxified/eliminated by    liver
      Fatty liver
    
    
      Adrenal hyperplasia
      Hypothalamic-Pituitary-Adrenal axis (HPA axis) dysregulation
      Chronic elevated cortisol production
      Chronic sympathetic nervous system response
      Anxiety
      Insomnia
      Fatigue
      Produce excess androgens due to insulin resistance
      Weight gain
      Increased risk of heart disease and stroke
    
    
      Hypothyroidism
      Fatigue
      Increased Thyroid Stimulating Hormone and prolactin production
      Prolactin causes anovulation and abdominal obesity
      Deceased circulation to distal extremities: disruption in    temperature regulation
      Dysregulation of basal metabolic rate: changes in heart rate, blood    pressure, respiratory rate



Table 2: Endocrine organs affected by polycystic ovarian syndrome [3-6].

Table 3: Systems affected by polycystic ovarian syndrome [7-13].




  
    Systems
    Gastrointestinal System [7-10] 
    Lymphatic System/Skin [7,8] 
    Reproductive System [11-13] 
  
  
    Symptoms/

      Side Effects
    
      Decreased diversity of gut microbiota
      Increased non-beneficial gut bacteria
      Chronic inflammation damages intestinal lining
      Decreased nutritional absorbance
      Decreased immunity
      Increased risk of metabolic diseases
      Gastrointestinal hormone dysfunction
      Gas, bloating, Gastrointestinal (GI) upset
      Irritable bowel syndrome
      Abnormal Central Nervous System (CNS)-gut axis
      Decreased serotonin production by intestinal enterochromaffin    cells: increased psychological disorders
      Eating disorders
    
    
      Elimination dysfunction
      Cystic acne
      Eczema
      Skin bacterial infections
    
    
      Hyperandrogenism and Hypoestrogenism
      Androgenic alopecia
      Hirsutism
      Anovulation
      Oligomenorrhea/Amenorrhea
      Polycystic ovaries
      Central obesity
      Decreased sex drive
      Infertility
      Pregnancy issues: preterm delivery, miscarriages, pre-eclampsia,    gestational diabetes
      Ovulatory disorders
      Autoimmune disorders due to hypoestrogenic state
      Endometriosis/endometrial cancer
      Elevated luteinizing hormone production: compromises oocyte    development and pancreatic function



Table 3: Systems affected by polycystic ovarian syndrome [7-13].

The Role of chronic inflammation in polycystic ovarian syndrome

Women with PCOS experience a chronic inflammatory state due a disproportionate ratio of inflammatory markers to antiinflammatory metabolites [14]. PCOS is characterized by increased levels of inflammatory markers including C-reactive protein (CRP) and Alpha(1)-acid glycoprotein [1,14]. Elevated levels of proinflammatory markers are due to hyperandrogenism, and increased adipose tissue forms as a result of insulin resistance (IR) in women with PCOS [1,14]. Albumin and adiponectin are anti-inflammatory agents that are lower in women with PCOS [14]. As a result, there is increased CRP/albumin ratio due to hyperandrogenism’s positive impact on liver synthesis of CRP [14]. Long term health effects due to the unequal ratio of inflammatory and anti-inflammatory markers are obesity, insulin resistance, type 2 diabetes, cardiovascular disease, and metabolic dysfunction [1,14].

Interventions to reduce inflammation in PCOS patients include reducing hyperandrogenism and insulin resistance [1,14]. Insulin sensitizers including Metformin and Myo-inositol have been shown to improve insulin sensitivity [15,16]. When comparing Metformin and Myo-inositol, Metformin has several gastrointestinal side effects. In addition, Myo-inositol has regulatory reproductive effects including normalizing menstrual cycles and ovulation in women with PCOS [16]. Oral contraceptives used to treat PCOS further exacerbate insulin resistance and hyperandrogenism, as well as disrupts normal reproductive system functioning [7].

A healthy diet and supplementation of essential macro and micronutrients in women with PCOS is vital to the reduction of this chronic inflammatory state [17]. High fiber diets contain inositol, which is utilized to reduce IR and the risk of developing metabolic abnormalities [17]. Diets that include unrefined complex carbohydrates and low amounts of simple sugars improve pancreatic insulin sensitivity, regulate menstrual cycles, as well as reduce the production of pro-inflammatory markers, hyperandrogenism, and increase gut microbiome diversity [8,17]. Diets with elevated levels of saturated fats, such as red meats, do fail to promote normal levels of insulin and glucose [17].

As far as supplementation, curcumin reduces inflammation and the prevalence of IR when used in conjunction with Metformin [17]. Chromium also reduces IR, and promotes normal ovulation [17]. Vitamin D, B12, and folate reduce IR [18]. Zinc, magnesium, and selenium improve serum glucose levels [17].

Exercise reduces the risk of developing IR and hyperandrogenism in women with PCOS [18]. There is minimal evidence related to exercise standards for women with PCOS; therefore, it is recommended that women with PCOS achieve 150 min of moderate physical activity per week [2]. However, this guideline does not consider the cyclic hormonal changes women experience, and how to best align exercise with optimal endocrine and reproductive function [19]. In follicular and ovulatory phases, women experience fewer hormonal symptoms and higher levels of estrogen, which makes them better suited to participate in high-intensity exercise [19,20]. This is due to estrogen’s positive impact on glucose availability and nerve conduction [20]. During the luteal phase, high levels of progesterone have the opposite effect of estrogen [20]. During the end of the luteal phase and menstrual phase, women experience more hormonal symptoms and less energy to perform high-intensity exercise [19]. More research is needed to identify the most beneficial types of physical activity during different phases of the menstrual cycle [2].

The role of hypothalamic pituitary axis dysregulation and psychological disorders in the chronic inflammatory state of women with polycystic ovarian syndrome

Women with PCOS have an increased risk of developing depression and anxiety [21,22]. Chronic hyperandrogenism causes a negative body image, which contributes to the development of these psychological disorders [11,21,22]. Elevated serum cortisol levels due to hypothalamic-pituitary-adrenal (HPA) axis dysregulation and adrenal gland overstimulation in women with PCOS leads to hyperandrogenism and psychological disorders [21,22].

Additionally, chronic stress causes sympathetic nervous system activation and an overactive HPA axis [5,23]. Women with PCOS are unable to inhibit this chronic sympathetic response; therefore, adrenal fatigue, anxiety, depression, and exacerbated chronic disease symptoms ensue [5,23]. Inflammation also increases in response to chronic stress [23,24]. Abdominal obesity in women with PCOS is in response to HPA axis dysregulation, which increases inflammatory markers [23,24]. This contributes to the unequal ratio between inflammatory makers and anti-inflammatory agents [23,24].

Interventions to reduce the prevalence of psychological disorders in women with PCOS include cognitive-behavioral therapy (CBT) [25]. CBT in conjunction with a nutritious diet and adequate physical activity have been proven to increase quality of life and psychological health in women with PCOS [25,26]. Yoga is one example of a form of exercise that, in conjunction with a holistic medical approach, improves emotional well-being and endocrine function [27]. Overall, routine psychological well-being assessments and services are recommended for women with PCOS [2].

The role of chronic inflammation in polycystic ovarian syndrome’s gut microbiota state

The gut microbiome (GM) contains a diverse group of bacteria that support digestive system processes as well as regulation of other endocrine organs [8]. A healthy GM is responsible for nutritional absorption through the small intestine and improving immunity against pathogens [8]. Women with PCOS lack a diverse GM, making them more susceptible to nutritional deficiencies, contracting harmful pathogens, and abnormal production of androgens [7,8]. Additionally, there are more non-beneficial types of GM bacteria, leading to an immunocompromised and chronic inflammatory state in women with PCOS [7]. An increase in non-beneficial types of GM bacteria also causes a decrease in insulin sensitivity, which in turn leads to abdominal obesity [7].

Due to the chronic inflammatory state in women with PCOS, the gastrointestinal lining becomes damaged and is more susceptible to diffusion of substances across its barrier [8]. As a result of this damage of the lining, toxins are released into the bloodstream [7]. This continual damage to the beneficial intestinal lining intensifies PCOS symptoms [7].

A normal Central Nervous System (CNS)-gut axis is essential in decreasing the risk of developing psychological disorders in women with PCOS [7,8]. Women with PCOS have an abnormal CNS-gut axis due to less diversity of their GM and chronic damage to their intestinal lining [7,8]. Damage to the intestinal lining decreases the amount of intestinal enterochromaffin cells that produce serotonin [7,8]. Decreased levels of serotonin cause dysfunction of psychoendocrinological processes associated with HPA axis regulation and cognitive development [7,8].

Due to the significant impact an abnormal GM has on digestive and other endocrine processes, gut health intervention is an essential part of the holistic treatment of PCOS [17]. Diets high in fiber content protect the intestinal lining from damage and inflammation, reduce the abnormal production of androgens, increases nutritional absorption, and improves overall immunity [7,8,17]. In addition, supplementation of probiotics and prebiotics aids in regulation of the GM in women with PCOS [4,7]. Probiotics decrease inflammation as well as increase immunity [7]. Probiotics and prebiotics have regulatory reproductive effects, including regulating ovulation and decreasing hyperandrogenism [4].

Conclusion

Polycystic ovarian syndrome is a complex and highly interconnected endocrine and gynecological disorder. A holistic healthcare approach should be taken to treat the underlying organ dysfunction associated with PCOS symptoms. This includes interprofessional collaboration between primary care physicians, endocrinologists, gynecologists, and psychologists. Lifestyle modifications including proper diet and supplementation, medications, stress management, and exercise are needed to reduce chronic inflammation and the risk of developing psychological disorders, as well as improving gut microbiota diversity. Women with PCOS can achieve a high quality of life and a decreased risk of developing comorbidities if diagnosed early and provided proper treatment.

References

Download PDF

Citation:Davis CC and Popp JK. The Role of Polycystic Ovarian Syndrome in Chronic Inflammation, Psychological Health, and the Gut Microbiota State: A Case Report. J Fam Med. 2022; 9(1): 1285.

Home

Journal Scope

Abstract Board

Instruction for Authors

Submit Your Article

Endocrine Organs	Pancreas [3,4]	Liver [3]	Adrenal glands [5]	Thyroid gland [6]
Symptoms/Side Effects	Insulin resistance Excess insulin production: abnormal production of androgens by ovaries and adrenals Hypoglycemia Increased risk of type 2 diabetes/metabolic disorder Central obesity Chronic inflammation	Elevated blood lipid levels Risk of cardiovascular disorders Increased demand on liver Elevated estrogen levels: need to be detoxified/eliminated by liver Fatty liver	Adrenal hyperplasia Hypothalamic-Pituitary-Adrenal axis (HPA axis) dysregulation Chronic elevated cortisol production Chronic sympathetic nervous system response Anxiety Insomnia Fatigue Produce excess androgens due to insulin resistance Weight gain Increased risk of heart disease and stroke	Hypothyroidism Fatigue Increased Thyroid Stimulating Hormone and prolactin production Prolactin causes anovulation and abdominal obesity Deceased circulation to distal extremities: disruption in temperature regulation Dysregulation of basal metabolic rate: changes in heart rate, blood pressure, respiratory rate

Systems	Gastrointestinal System [7-10]	Lymphatic System/Skin [7,8]	Reproductive System [11-13]
Symptoms/ Side Effects	Decreased diversity of gut microbiota Increased non-beneficial gut bacteria Chronic inflammation damages intestinal lining Decreased nutritional absorbance Decreased immunity Increased risk of metabolic diseases Gastrointestinal hormone dysfunction Gas, bloating, Gastrointestinal (GI) upset Irritable bowel syndrome Abnormal Central Nervous System (CNS)-gut axis Decreased serotonin production by intestinal enterochromaffin cells: increased psychological disorders Eating disorders	Elimination dysfunction Cystic acne Eczema Skin bacterial infections	Hyperandrogenism and Hypoestrogenism Androgenic alopecia Hirsutism Anovulation Oligomenorrhea/Amenorrhea Polycystic ovaries Central obesity Decreased sex drive Infertility Pregnancy issues: preterm delivery, miscarriages, pre-eclampsia, gestational diabetes Ovulatory disorders Autoimmune disorders due to hypoestrogenic state Endometriosis/endometrial cancer Elevated luteinizing hormone production: compromises oocyte development and pancreatic function