GENETIC IMPLICATIONS OF POLYCYSTIC OVARY SYNDROME

PCOS

BY

BEKIE EMMANUELLA CHIDINMA

REG. NO: EBSU/2018/92928

SUPERVISOR; DR. SIMON UZOR

A SEMINAR PRESENTED TO THE DEPARTMENT OF MEDICAL

IN FUFILMENT OF THE AWARD OF BARCHELOR OF MEDICAL

JULY, 2023.
INTRODUCTION:

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder affecting women of

reproductive age. It is characterized by hormonal imbalances, irregular menstrual cycles, cystic

ovaries, and often leads to infertility. While the exact cause of PCOS remains unclear, increasing

evidence suggests a significant genetic component in its etiology. This seminar will explore the

genetic implications of PCOS, with a specific focus on its association with the Fat Mass and

Obesity-associated (FTO) gene.

PCOS is a complex condition, and its clinical features can vary between individuals. The three

main features used to diagnose PCOS are known as the Rotterdam criteria, and a woman must

exhibit at least two of the following three features for diagnosis:

1. Oligo-ovulation or Anovulation: This refers to irregular or absent menstrual cycles,

which can lead to difficulties in predicting ovulation and causing fertility problems.

Women with PCOS may experience infrequent periods or even have prolonged periods of

amenorrhea (absence of menstruation).

2. Clinical and/or Biochemical Hyperandrogenism: Hyperandrogenism refers to higher than

normal levels of androgens, which are male hormones that are also present in females,

but in smaller amounts. Clinical manifestations of hyperandrogenism may include

hirsutism (excessive hair growth on the face, chest, abdomen, and back), acne, and male-

pattern hair loss (androgenic alopecia). Biochemical hyperandrogenism can be confirmed

through blood tests showing elevated levels of androgens like testosterone.

3. Polycystic Ovaries: On ultrasound imaging, the ovaries may appear enlarged and contain

multiple small follicles (fluid-filled sacs). These follicles give the appearance of a "string
 of pearls" and are a characteristic feature, though not all women with PCOS will have

polycystic ovaries.

Other clinical features and associated symptoms of PCOS may include:

 Weight gain or obesity: Many women with PCOS are overweight or obese, and there is

often a correlation between PCOS and insulin resistance, which contributes to weight

gain.

 Insulin resistance: This is a condition where the body's cells do not respond effectively to

insulin, leading to elevated blood sugar levels. Insulin resistance can contribute to

metabolic disturbances and may be associated with an increased risk of developing type 2

diabetes.

 Acanthosis nigricans: Darkening and thickening of the skin, often in skin folds like the

neck, armpits, and groin areas, which can be associated with insulin resistance.

 Mood swings and depression: PCOS may have a negative impact on emotional well-

being and contribute to mood disturbances.

It is important to note that the clinical presentation of PCOS can vary, and not all individuals will

experience all of these features. Additionally, the severity of symptoms can differ from woman

to woman. Early diagnosis and appropriate management are essential to address the associated

health concerns and improve quality of life for women with PCOS. If you suspect you may have

PCOS or are experiencing any of these symptoms, it is crucial to seek medical evaluation and

guidance from a healthcare professional.

Polycystic Ovary Syndrome (PCOS) is a heterogeneous condition, meaning it can present in

different ways and have varying underlying causes. Over the years, researchers and clinicians

have recognized different classifications or phenotypes of PCOS based on the predominant

clinical features and hormonal patterns. The two main classification systems are the Rotterdam

criteria and the Androgen Excess and PCOS Society (AE-PCOS Society) criteria. Let's explore

the types of PCOS based on these classification systems:

1. Rotterdam Criteria-based Classification: The Rotterdam criteria were established in 2003

and are the most widely used classification system for PCOS. According to these criteria,

a woman must meet at least two of the following three features for a PCOS diagnosis:

a. Oligo-ovulation or Anovulation: Irregular or absent menstrual cycles, which can lead to

fertility problems.

b. Clinical and/or Biochemical Hyperandrogenism: Manifestations include hirsutism (excessive

hair growth on the face, chest, abdomen, and back), acne, and male-pattern hair loss (androgenic

alopecia). Biochemical hyperandrogenism can be confirmed through blood tests showing

elevated levels of androgens like testosterone.

c. Polycystic Ovaries: Seen on ultrasound imaging, ovaries may appear enlarged and contain

multiple small follicles (fluid-filled sacs).

Based on the combination of these features, PCOS is classified into four types:

 Type 1: Oligo-anovulation and hyperandrogenism but no polycystic ovaries.

 Type 3: Hyperandrogenism and polycystic ovaries but normal ovulation.

 Type 4: All three features present - oligo-anovulation, hyperandrogenism, and polycystic

ovaries.

2. AE-PCOS Society Criteria-based Classification: The Androgen Excess and PCOS

Society (AE-PCOS Society) published updated criteria in 2006 and 2013. According to

these criteria, PCOS is diagnosed if a woman exhibits both hyperandrogenism (clinical

and/or biochemical) and ovarian dysfunction (oligo-anovulation or polycystic ovaries).

The AE-PCOS Society does not require the presence of polycystic ovaries as a

mandatory criterion for diagnosis, recognizing that some women with PCOS may not

have this ultrasound finding.

Based on the clinical presentation, AE-PCOS Society classified PCOS into two types:

 Phenotype A: Hyperandrogenism with oligo-anovulation (classic PCOS).

 Phenotype B: Hyperandrogenism with polycystic ovaries but normal ovulation.

It is important to note that while these classification systems are helpful for research and clinical

management, PCOS remains a complex and multifaceted condition. Women with PCOS may

have unique presentations and different underlying pathophysiological mechanisms contributing

to their symptoms. Tailored management approaches are essential for addressing the specific

needs of each individual with PCOS. If you suspect you have PCOS or are experiencing any

related symptoms, consult a healthcare professional for proper evaluation and diagnosis.

Muhammad (2015)
CAUSES OF PCOS

The exact cause of Polycystic Ovary Syndrome (PCOS) remains not fully understood, and it is

likely to be influenced by a combination of genetic, hormonal, and environmental factors.

Researchers have identified several potential causes and contributing factors to the development

of PCOS. Some of these include:

1. Genetic Factors: There appears to be a significant genetic component to PCOS. Women

with a family history of PCOS are more likely to develop the condition, suggesting a

hereditary predisposition. Specific genes that regulate hormonal pathways, insulin action,

and ovarian function have been implicated in PCOS. Diamanti-Kandarakis (2019)

2. Hormonal Imbalances: PCOS is characterized by hormonal disturbances, including

increased androgen (male hormone) levels and altered levels of gonadotropins

(luteinizing hormone - LH and follicle-stimulating hormone - FSH). The elevated

androgen levels can disrupt the normal menstrual cycle and lead to anovulation (lack of

ovulation) and the development of ovarian cysts. Rasu et al (2015)

3. Insulin Resistance: Many women with PCOS also have insulin resistance, a condition in

which the body's cells do not respond effectively to insulin. Insulin resistance leads to

increased insulin production by the pancreas, which, in turn, can cause the ovaries to

produce more androgens. The excess androgens can then disrupt ovulation and lead to

PCOS symptoms.
 4. Inflammation: Chronic low-grade inflammation may play a role in PCOS development.

Inflammation can contribute to insulin resistance and androgen production, further

exacerbating the hormonal imbalances associated with PCOS.

5. Lifestyle and Environmental Factors: Obesity and sedentary lifestyles have been linked to

an increased risk of PCOS. Excess body fat can worsen insulin resistance and hormonal

imbalances. Environmental factors, such as exposure to endocrine-disrupting chemicals

(EDCs), have also been suggested to play a role in PCOS development.

6. Fetal Origins Hypothesis: Some researchers propose that PCOS may have origins in fetal

development. Exposures to certain environmental factors or maternal hormonal

imbalances during pregnancy could influence the development of the female fetus's

reproductive system, leading to PCOS later in life. Lizneva et al (2016)

PREVENTION OF PCOS

it's important to note that Polycystic Ovary Syndrome (PCOS) is a complex and multifactorial

condition, and there is no surefire way to prevent its development. However, certain lifestyle

changes and proactive measures may help reduce the risk of developing PCOS or mitigate its

symptoms. Here are some potential strategies for prevention:

1. Maintain a Healthy Weight: Since obesity and excess body fat are associated with an

increased risk of PCOS, maintaining a healthy weight through a balanced diet and regular

exercise may be beneficial. Weight loss, if needed, may help improve insulin sensitivity

and hormone levels, potentially reducing the risk of PCOS or alleviating its symptoms.
2. Adopt a Balanced Diet: A diet that emphasizes whole foods, including fruits, vegetables,

whole grains, lean proteins, and healthy fats, can support overall health and may help

regulate insulin levels. Reducing the consumption of highly processed and sugary foods

can be particularly helpful in managing insulin resistance.

3. Regular Physical Activity: Engaging in regular physical activity can aid in weight

management, improve insulin sensitivity, and help regulate hormonal balance. Aim for at

least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-

intensity aerobic activity per week, along with muscle-strengthening exercises on two or

more days a week.

4. Avoid Smoking and Excessive Alcohol Consumption: Smoking and excessive alcohol

intake have been associated with hormonal imbalances and may worsen insulin

resistance. Avoiding these habits can promote better overall health.

5. Manage Stress: Chronic stress can impact hormone levels and exacerbate insulin

resistance. Adopt stress-reducing techniques such as mindfulness, yoga, meditation, or

engaging in hobbies to help manage stress.

6. Regular Health Check-ups: Regular health check-ups and screenings can help detect and

manage any potential health issues, including early signs of PCOS.

7. Consult a Healthcare Professional: If you have irregular menstrual cycles, experience

signs of hyperandrogenism (such as hirsutism, acne, or hair loss), or suspect you may

have PCOS, it's essential to consult a healthcare professional. Early diagnosis and

appropriate management can help mitigate symptoms and reduce the risk of long-term

complications.
CLINICAL IMPORTANCE

Polycystic Ovary Syndrome (PCOS) is of significant clinical importance due to its prevalence,

impact on women's health, and associated complications. Understanding the clinical implications

of PCOS is crucial for early detection, appropriate management, and prevention of long-term

health risks. Here are some key aspects highlighting the clinical importance of PCOS:

1. Prevalence and Impact: PCOS is one of the most common endocrine disorders affecting

women of reproductive age. Its prevalence varies across populations but is estimated to

affect approximately 5-10% of women worldwide. PCOS can have a profound impact on

a woman's physical and emotional well-being, affecting her fertility, menstrual regularity,

body image, and overall quality of life.

2. Reproductive Health and Fertility: PCOS is a leading cause of female infertility due to

hormonal imbalances and anovulation (lack of ovulation). Women with PCOS may have

difficulties conceiving naturally and often require medical assistance, such as ovulation-

inducing medications or assisted reproductive technologies (ART) like in vitro

fertilization (IVF), to achieve pregnancy.

3. Menstrual Irregularities: Irregular or absent menstrual cycles are common in PCOS.

These irregularities can lead to difficulties in predicting ovulation, challenges in family

planning, and potential concerns about endometrial health.

4. Metabolic Complications: PCOS is associated with an increased risk of metabolic

disturbances, such as insulin resistance, impaired glucose tolerance, and type 2 diabetes.

Insulin resistance can contribute to weight gain and difficulty losing weight, making

women with PCOS more susceptible to obesity and its associated health risks.
 5. Cardiovascular Risk: Women with PCOS have an elevated risk of developing

cardiovascular diseases, including hypertension, dyslipidemia (abnormal cholesterol

levels), and early atherosclerosis. These cardiovascular risk factors may further increase

the likelihood of heart disease later in life.

6. Psychological and Emotional Well-being: PCOS can have a substantial impact on mental

health, leading to increased rates of anxiety, depression, and body image concerns. The

hormonal imbalances and challenges associated with fertility and weight management

can contribute to emotional distress in affected individuals.

7. Long-term Health Risks: Women with PCOS may be at higher risk of developing other

health conditions, such as non-alcoholic fatty liver disease (NAFLD), sleep apnea, and

endometrial hyperplasia (a thickening of the uterine lining) due to irregular menstrual

cycles and hormonal imbalances.

8. Screening and Early Detection: Early detection and diagnosis of PCOS are essential for

appropriate management and to address potential complications. Regular health check-

ups, blood tests, and ultrasound evaluations can aid in identifying PCOS in its early

stages.

9. Individualized Treatment Approach: PCOS is a complex condition with various

presentations. A personalized and multidisciplinary approach to management, including

lifestyle modifications, hormonal therapy, and infertility treatments, can help improve

outcomes and quality of life for women with PCOS.

EPIDEMIOLOGY OF PCOS
The epidemiology of Polycystic Ovary Syndrome (PCOS) highlights its prevalence, distribution,

and impact on various populations. PCOS is a common endocrine disorder, and its epidemiology

varies across different regions and ethnicities. Here are some key epidemiological aspects of

PCOS:

1. Prevalence: PCOS is one of the most prevalent endocrine disorders among women of

reproductive age. The reported prevalence varies depending on the diagnostic criteria

used and the population studied. Globally, PCOS is estimated to affect approximately 5-

10% of women of reproductive age. However, some studies have reported higher

prevalence rates in specific populations.

2. Age of Onset: PCOS typically begins during adolescence, around the time of menarche,

but can manifest at any age during the reproductive years. Signs and symptoms often

become more evident in the late teens or early 20s.

3. Ethnic Differences: PCOS prevalence and presentation can vary among different ethnic

and racial groups. Some studies have suggested that certain ethnicities, such as South

Asians, have a higher prevalence of PCOS compared to other populations.

4. Diagnostic Criteria: The diagnosis of PCOS is based on clinical, hormonal, and

ultrasound criteria. The most widely used diagnostic criteria are the Rotterdam criteria,

which require the presence of at least two out of three features: oligo-anovulation, clinical

and/or biochemical hyperandrogenism, and polycystic ovaries on ultrasound.

5. Impact on Fertility: PCOS is a leading cause of female infertility. The hormonal

imbalances and anovulation associated with PCOS can make it challenging for women to

conceive naturally, requiring medical intervention and fertility treatments to achieve

pregnancy.
6. Associated Comorbidities: PCOS is often associated with various metabolic and

cardiovascular comorbidities, including insulin resistance, impaired glucose tolerance,

type 2 diabetes, dyslipidemia, hypertension, and obesity. These comorbidities contribute

to the increased risk of long-term health complications.

7. Psychological Impact: PCOS can also have significant psychological implications, with

affected individuals experiencing higher rates of anxiety, depression, and body image

concerns.

8. Family History: There is evidence to suggest a familial predisposition to PCOS, with a

higher risk of developing the condition in women with a family history of PCOS.

9. Underdiagnosis and Misdiagnosis: Despite its prevalence, PCOS is often underdiagnosed

or misdiagnosed, as its symptoms can be mistaken for other conditions. Increased

awareness among healthcare providers and improved diagnostic methods are essential to

address this issue.

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