Diagnosis, causal factors and associated diseases of PCOS: A Mini-review

 

Sanasam Birjeni Devi1, C. Susila2

1Department of Nursing, Bareilly International University, Utter Pradesh-243006, India.

2Billroth College of Nursing, No.2 Mettukuppam Road, Maduravoyal, Chennai - 600095, Tamil Nadu, India.

*Corresponding Author Email: sanasambirjenidevi@gmail.com

 

ABSTRACT:

Polycystic ovary syndrome (PCOS) is a hormonal imbalance disorder, occurring commonly in women of reproductive age, which leads to infertility. Around 12-18% of women of reproductive age are affected by PCOS and up to 21% of women are at high risk. Although, the origin of PCOS is unknown and can’t be pinpointed; its onset is indisputably associated with several factors including genetics, lifestyles, hormonal, etc. Changes during the adolescent period have important indications to understand the health risks associated with this syndrome. Women with PCOS usually suffer from chronic anovulation and hyper-androgenism, which are the main noticeable indicators associated with PCOS and it results in pregnancy problems. Therefore, PCOS poses a great deal to women in their reproductive stage, which demands deep understanding and proper strategies that can be implemented to women with PCOS, to nurse the body back to fertility. PCOS being a syndrome comprising many symptoms, its treatment and management is mainly based on dealing the associated symptoms individually. In this review article, important causing factors, diagnostic criteria, and pathophysiology of PCOS along with important findings from recent studies are being discussed and highlighted.

 

KEYWORDS: PCOS, Infertility, Hormonal imbalance, Anovulation, Obesity.

 

 


BACKGROUND INTRODUCTION

PCOS is one of the most common concerns among women of reproductive age. PCOS being a complex multifactorial disorder, is thought to be surfaced from a complex interaction involving both genetics and environmental factors1. Maybe due to idle unhealthy indoor lifestyle mainly obese women are more prone to PCOS and other hormonal disorders2. Some of the common symptoms associated with PCOS are irregular menstrual cycle, acne, hirsutism, excess hair fall, depression, weight gain, etc3. According to Rotterdam’s criteria, out of the three main characteristics for diagnosing PCOS: hyperandrogenism, oligo-ovulation, and polycystic ovaries visible on ultrasound, at least two criteria should be fulfilled4.

 

Even with the development of high technology and medical science, there remain many uncertainties that pose challenges in the diagnosis and treatment of PCOS.  PCOS is usually associated with fertility difficulties; therefore, the main concern of many of the patients with PCOS is whether they will be unable to become pregnant5. Since, PCOS is a syndrome comprising various symptoms; its treatment is totally symptomatic. Lack of awareness and unhealthy lifestyle is considered to be the main factor resulting in this phenomenon6,7. Therefore, there is a need to increase awareness among women to avoid major causes of infertility in the future3,8.

 

Diagnosis and Diagnostic Criteria of Pcos:

Symptoms of PCOS usually appear during puberty. And it is often diagnosed by clinical criteria such as menstrual dysfunction and clinical hyperandrogenism; which means that PCOS patients may have prolonged or infrequent menstrual periods or elevated androgen levels9. Therefore, hyperandrogenism (biochemical or clinical), along with ovarian dysfunction, comprising both functional and ultrasonographic abnormalities, is the key characteristic of PCOS10. There is no specific diagnostic test that indisputably pinpoints PCOS; rather the diagnosis is based on the varying presence of the above aforementioned 3 specific elements, namely oligo-anovulation, excess androgen, and the ultrasound assessment of ovarian morphology (multiple cysts)10,11. For the diagnosis in adult women, the use of the Rotterdam criteria is recommended that requires 2 of the 3 diagnostic criteria be fulfilled in addition to the exclusion of other familiar diseases that could result in hyperandrogenism or ovulatory dysfunction4.

 

Exclusion of other similar symptomatic disorders:

PCOS is a diagnosis of exclusion and there's no single test or technique to definitively diagnose PCOS, hence it demands to rule out common ailments that could display similar symptoms. PCOS symptoms overlap other symptomatic hormonal disorder cases like hyperprolactinemia, thyroid disease, and non-classic congenital adrenal hyperplasia, which need to be excluded during the diagnosis12. Further evaluation is necessary to check for hypogonadotropic hypogonadism, Cushing’s disease, or androgen-secreting tumors depending on the patient’s presentation13. Assessment of PCOS should also eliminate other androgen-excess conditions and possible aspects for endometrial cancer, diabetes, obstructive sleep apnea mood disorders, and cardiovascular disease14. Hence, the exclusion of other nosologic ailments resembling the clinical exhibition of PCOS is of utmost importance and the basis of PCOS diagnosis.

 

Challenges in the diagnosis of PCOS in adolescents:

Adolescence symbolizes the time duration which pubertal maturation occurs and it represents a challenging stage in the diagnosis of PCOS. PCOS diagnosis in adolescents is tough because physiologic changes that took place during puberty are similar to the symptoms of PCOS9. The common features of normal puberty, namely acne, menstrual irregularities, and insulin resistance overlaps that of PCOS symptoms and thus putting a hurdle in diagnosing PCOS15. During puberty, menstrual irregularities such as anovulation or varied length of the menstrual cycle are very common, since the hypothalamic-pituitary-ovarian axis is still immature in this stage. Moreover, multi-cystic ovaries are a frequent condition in the adolescent period. Owing to all these overlapping features, there is the risk of both under-diagnosis and that of over-diagnosis without adequate support for disease16. Currently, there are no recognized PCOS’s diagnostic criteria for this age group, but different criteria for diagnosis of PCOS in adolescents have been suggested. For the diagnosis of PCOS in adolescents, Sultan and Paris (2006) recommended the presence of four out of five criteria i.e. hyperinsulinism, clinical hyperandrogenism and biologic hyperandrogenism, oligo-menorrhea or amenorrhea, and polycystic ovaries on ultra-sonography17. In addition, sign of anxiety and depression should be checked and  eating disorders or bad eating habits should also be considered18. Polycystic ovarian morphology on ultrasound without menstrual irregularities or hyperandrogenism should not be used to diagnose PCOS in adolescence as large, multi-cystic ovaries are a commonly found in the adolescent period, so ultrasound is not dependable, meanwhile, ovarian imaging is also problematic in the adolescent group, since the trans-vaginal ultrasound approach does not apply to virgin19. Therefore, diagnostic features for adolescent girls are mainly based on menstrual irregularity, clinical hyperandrogenism, and/or hyperandrogenemia9.

 

Pathophysiology and Causal Factors Associated with Pcos:

The pathogenesis of PCOS is complex and multifactorial, which has several aspects in terms of pathology involving endocrine, metabolic, reproductive, and psychological. Causal factors include genetic, environmental, and other trans-generational components20. These sources bring about an unbalanced gonadotropin-ovarian axis, which stimulates ovarian and adrenal hyperandrogenism21. The syndrome is also burdened with insulin resistance that is worsened by hyperandrogenism related adipose tissue accumulation and dysfunction with lipotoxicity and oxidative stress. Therefore, PCOS comprises a broad clinical set of syndromes involving reproductive, metabolic, and psychological disorders.

 

Psychological/Anxiety and depression:

PCOS is associated with higher chances of psychiatric disorders and is related to increased psychological distress in clinical populations. Although only limited data are available regarding the perseverance of depression and anxiety symptoms in adolescents, it has been reported that psychological distress has a role in PCOS, if prevailing long-term. A cross-sectional study by Damone et al. (2018) has shown that compared with non-PCOS women, women reporting PCOS have increased depression, anxiety, and perceived stress which indicate the role that may be played by stress22. In addition, women with PCOS are found to have a greater prevalence of bad or disordered eating habits and body image distress which further add difficulty in losing weight.  Further, lower sleep quality was also discovered in women with PCOS which was mainly stemmed from body image distress23. Considering all these, mental disorders or psychological distress should be tested and intervened by adopting appropriate therapy.

 

Genetical factors:

PCOS can be defined as a genetic disorder that involves many genes and factors, affecting the fertility of reproductive women, directly or indirectly. Many candidate genes responsible for PCOS have been identified so far24. Investigations on oligomenorrhoeic adolescents have suggested the presence of biochemical markers of PCOS that will eventually advance the further clinical features of the syndrome. And there is a high chance of inheriting the condition by a child from a parent carrying the gene, thus, infant girls born to PCOS mothers have higher metabolic and androgenic risk1,6. Further, prenatal androgen exposure is suspected to increase susceptibility to PCOS in the daughters. Hyperandrogenism is causatively linked with anovulation in PCOS and it originates mainly from defective hyperactive theca cells as well as neuroendocrine dysfunction. And owing to the complex pathophysiology comprising several proteins and pathways, there are no single genetic diagnostic tests.

 

Hormonal imbalance:

Hormonal imbalance is the main characteristic of women with PCOS. Hormones, including androgens, gonadotrophin-releasing hormone (GnRH), luteinizing hormone (LH), insulin, follicle-stimulating hormone, estrogens, cortisol, growth hormones (GH), parathyroid hormone (PTH), and calcitonin are found to be disturbed in PCOS women21,25. This misbalance of hormones in PCOS women results in an increased incidence of osteoporosis 26. The persistent hormonal misbalance leads to the complications such as polycystic ovaries, an irregular menstrual cycle that eventually leads to infertility in females.

 

Role of obesity:

Obesity is often connected with PCOS since they often co-exist and come together. The link between obesity and the prevalence of PCOS is highly correlated and potentially bidirectional since women with PCOS are often obese or overweight. Therefore it is often debated whether women are obese because of PCOS or the other way round2. Studies have shown a high prevalence of hyperandrogenemia among females with obesity, suggesting the risk induced by obesity in developing PCOS, further, obesity elevates the severity of the reproductive, metabolic, and psychological features of PCOS27. Therefore, weight loss is an important therapeutic target in obese PCOS patients, weight loss and lifestyle intervention are often recommended in obese PCOS patients as it is beneficial in PCOS and other health benefits14,28.

 

Lifestyles and environment factors:

PCOS is a polyfactorial, dysregulated steroid state establishing mostly because of lifestyle errors29. In addition to genetic factors, environmental factors contribute equally to PCOS pathogenesis. Studies have revealed that quality of life is one of the important factors inducing PCOS in women. Poor life quality indicates difficult, stressful life or sedentary life with poor nutrition or eating habits, which may result in some hormonal imbalance 6. Further, endocrine-disrupting chemicals namely, Bisphenol A (BPA), embodies possible environmental contributors, exposure to which might lead to PCOS pathogenesis. Elevated BPA concentrations have been detected in PCOS women and are directly correlated with hyperandrogenemia, indicating a potential role in PCOS pathophysiology30. Therefore, lifestyle and environmental factors including nutrition, mental health, exposures to chemicals all have their fair share in PCOS pathogenesis. Nutrients such as vitamins, vitamin-like nutrients, and minerals are suggested for the treatment of PCOS since each has its functional role in pathways involved in PCOS. And it is suggested that the origin of PCOS could be mineral or vitamin deficiency31.

 

Insulin Resistance and Other Associated Diseases:

Adolescents with PCOS are at high risk of attaining health problems later in the future, such as insulin resistance, dyslipidemia, diabetes, cardiovascular disease, systemic inflammation, endothelial dysfunction, infertility, and other health issues32–36. The mechanism of PCOS is yet to be fully understood, although PCOS is not essentially associated with obesity and insulin resistance, some studies have proposed that insulin resistance plays a crucial role in the advancement of PCOS pathophysiology21,37. PCOS patients are susceptible to developing glucose intolerance and diabetes mellitus type 2, as an outcome of declined insulin sensitivity, especially in obese women38. Therefore, common treatment tactics of PCOS are mainly based on lifestyle alteration, which includes diet, exercise, and nutrient supplementation therapy 31. Studies have demonstrated increased masked hypertension prevalence in patients with PCOS, which poses a strong threat for adverse cardiovascular events in the future39. Because PCOS may contribute to the earlier development of hypertension, therefore it is advisable to monitor blood pressure systematically, control known risk factors, and initiate the treatment of hypertension when the disease occurs40. Finally, as discussed earlier, PCOS is often accompanied by conditions like anovulation, hyperandrogenism, insulin tolerance, type II diabetes, hyperlipidemia, and obesity, all of these conditions are approved risk factors proven to instigate cancer. And endometrial cancer seems to be more frequent in women with PCOS. Therefore, PCOS has various health risks which demand a careful investigation to detect and prevent any following consequences as early as possible10.

 

Assessment of Pcos:

PCOS diagnosis is based on the existence of at least two of the three criteria i.e. hyperandrogenism (biological or clinical), chronic anovulation, and polycystic ovaries4. For which there is a need for careful clinical assessment of women’s history, physical examination, and laboratory evaluation, accentuating the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging. Diagnosis of PCOS is usually carried out by hormone profile tests or ultrasound. Free testosterone (T) levels should be preferably determined through equilibrium dialysis techniques to check the manifestation of androgen excess41. Serum anti-Müllerian hormone and 17-hydroxyprogesterone are also used for the diagnosis of PCOS. The presence of polycystic ovaries is determined by carrying out an ultrasound. If an ultrasound image shows 12 or more follicles in the ovary with a diameter of 2–9 mm, it signifies a polycystic ovary. Ovarian size over 10 mL or ovarian volume of ≥10 cm3 represents an increased ovary size42,43.

 

Management of Pcos:

As PCOS is a syndrome that comprises various symptoms, it needs a detailed long-term management plan and a multi-prong approach to treat the accompanying symptoms. Therefore, its treatment is symptomatic and its management includes dietary changes, weight loss, and vitamin D regulation, along with the treatment of hirsutism, acne, irregular menstrual cycle, ovarian cysts, and depression44.

 

Change in lifestyles and Stress control:

Many PCOS symptoms are controlled and improved by adopting positive lifestyle choices such as maintaining a healthy weight and controlling stress by exercising and doing yoga. And adopting a healthy diet by eating a ketogenic diet and avoiding junk foods is also important. Quality of life plays important role in inducing PCOS in women. Poor life quality represents difficult, stressful life or sedentary life with poor nutrition or eating habits, which may eventually result in some hormonal imbalance. A study by Angin et al. (2019) showed that the quality of life among infertile PCOS women is lowest in comparison to non-PCOS infertile women indicating the influence of quality of life in PCOS women6. Therefore, getting enough sleep, daily exercise, avoiding over thinking, and proper resting is of utmost importance to keep the body as well as the mind healthy.

 

Diet:

Improvements in the diet by replacing high cholesterol foods with a low glycemic diet which are rich in fiber, protein, and antioxidants can help in controlling PCOS symptoms by controlling weight gain, insulin level, and heart diseases. A case-control study by Eslamian et al. (2016) suggested the association between high dietary glycemic index (GI), glycemic load (GL), and low fiber intake with the prevalence of PCOS45. Hence low glycemic diet and DASH (dietary approaches to stop hypertension) diet such as whole grains, legumes, nuts, seeds, fruits, starchy vegetables, other unprocessed, low-carbohydrate foods, poultry, fish, etc., are recommended as they can be beneficial to the patients of PCOS. Fiber, lean proteins, and foods with organic whole soy are also recommended for PCOS patients as they are good for weight loss and fertility of women. And foods such as refined carbs, sugary beverages, processed foods, saturated/ trans-fats, and alcohol are advised to be avoided as they are associated with a health problem and will spike blood sugar and weight gain46. Hence, quantity (calorie excess leading to obesity), as well as quality of food intake, may promote the pathogenesis of PCOS and young patients should be encouraged to adopt balanced dietary habits.

 

Exercise and weight loss:

As mentioned earlier, obesity and the prevalence of PCOS is highly correlated and the symptoms are worse with obese patients. Selvaraj et al. (2020) conducted a research to evaluate the effect of lifestyle modifications in minimizing PCOS risk and demonstrated that exercise and yoga are useful in reducing the risk of PCOS47. Furthermore, a study conducted by Tamilselvi et al. showed that adopting of the Self Help Strategies comprising mint tea, mint diet and exercise have significant effect in regulating hormones and also in weight loss48. Therefore, a balance diet and regular exercise for weight reduction is very important.

 

CONCLUSION:

PCOS is a very common reproductive disorder starting in early puberty and is associated with several health conditions and metabolic disorders. Since it is a multi-symptomatic disorder, there is still no single diagnostic test for PCOS. For the correct diagnosis of PCOS, careful clinical investigation of history, physical inspection, and laboratory assessment, accentuating the validity as well as the accuracy of the technique is required.  Further, if the disorder is not treated in time there is a high risk to develop infertility and other health issues. Therefore, awareness of PCOS, among women of reproductive age is important for early identification of the ‘environmental triggers’ and precursors of PCOS. Management of PCOS might include awareness or education regarding PCOS, healthy lifestyle, and therapeutic interventions targeting the symptoms.

 

CONFLICT OF INTEREST:

The authors declare no conflicting interest in publishing the article.

 

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Received on 06.06.2021           Modified on 28.07.2021

Accepted on 01.09.2021       ©A&V Publications All right reserved

Asian J. Nursing Education and Research. 2022; 12(1):138-143.

DOI: 10.52711/2349-2996.2022.00030