What is Polycystic Ovary Syndrome (PCOS)?

Polycystic Ovary Syndrome (PCOS)

PCOS is a common endocrine disorder affecting 8-13% of reproductive-age women, characterized by a combination of oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology, requiring at least two of these three Rotterdam criteria for diagnosis. 1

Definition and Prevalence

PCOS is the most common endocrine disorder in women of reproductive age, with prevalence ranging from 8-13% depending on the diagnostic criteria used. It represents a heterogeneous condition with varying presentations across a woman's lifespan 1. The prevalence is notably higher in women with temporal lobe epilepsy (10-25%) compared to the general population (4-6%), even without antiepileptic drug use 2.

Pathophysiology

The pathogenesis of PCOS involves:

• Acceleration of pulsatile gonadotropin-releasing hormone (GnRH) secretion
• Insulin resistance and hyperinsulinemia
• Hypersecretion of luteinizing hormone (LH)
• Ovarian theca stromal cell hyperactivity
• Hypofunction of the follicle-stimulating hormone (FSH)-granulosa cell axis
• Resulting hyperandrogenism and follicular arrest 2

Recent research suggests AMH (Anti-Müllerian Hormone) may have a possible causal role in PCOS development through in-utero exposure of the fetus to high AMH levels 2.

Diagnostic Criteria (Rotterdam)

To diagnose PCOS, two of the following three criteria must be present, with exclusion of other disorders:

1. Oligo/anovulation: Irregular or absent menstrual cycles
2. Clinical and/or biochemical hyperandrogenism:
   • Clinical: Hirsutism, acne, androgenic alopecia
   • Biochemical: Elevated testosterone, androstenedione, or DHEAS
3. Polycystic ovarian morphology (PCOM) on ultrasound:
   • Increased follicle number per ovary (FNPO)
   • Increased ovarian volume 1

Diagnostic Evaluation

Clinical Assessment

• Comprehensive history of menstrual irregularities
• Onset and duration of hyperandrogenic symptoms
• Distribution of body hair
• Medication use
• Lifestyle factors 1

Physical Examination

• Signs of hyperandrogenism (hirsutism, acne, androgenic alopecia)
• Evaluation for insulin resistance (acanthosis nigricans)
• Assessment for obesity and metabolic complications 1

Laboratory Testing

• First-line tests:

  • Total testosterone and free testosterone (preferably by LC-MS/MS)
  • Thyroid-stimulating hormone (TSH)
  • Prolactin
  • Two-hour oral glucose tolerance test with 75g glucose
  • Fasting lipid profile 1
  • Mid-luteal phase progesterone (levels <6 nmol/l indicate anovulation) 2

• Additional tests to exclude other conditions:

  • DHEAS (to rule out non-classical congenital adrenal hyperplasia)
  • Androstenedione (levels >10.0 nmol/l warrant investigation for adrenal/ovarian tumors)
  • Fasting glucose/insulin ratio (ratio >4 suggests reduced insulin sensitivity) 2

Imaging

• Transvaginal ultrasound (preferred) or transabdominal ultrasound
• Should report:
  • Total follicle number per ovary (2-9mm)
  • Three dimensions and volume of each ovary
  • Endometrial thickness and appearance 1
  • Characteristic findings: >10 peripheral cysts, 2-8mm diameter, with thickened ovarian stroma 2

Important note: Ultrasound is not recommended for PCOS diagnosis within 8 years of menarche due to overlap with normal multi-follicular appearance in adolescents 2. Additionally, serum AMH should not be used as an alternative for detecting PCOM or as a single test for PCOS diagnosis 1.

Differential Diagnosis

The diagnosis requires exclusion of other disorders including:

• Cushing's syndrome
• Androgen-secreting tumors
• Non-classic congenital adrenal hyperplasia
• Exogenous androgens
• Acromegaly
• Thyroid disorders
• Primary ovarian failure
• Hyperprolactinemia 1

Associated Complications

Women with PCOS have increased risk for:

• Type 2 diabetes and glucose intolerance
• Cardiovascular disease
• Endometrial cancer (OR 2.79) and ovarian cancer (OR 2.52) in women under 54 years
• Psychological disorders including anxiety and depression 1

Management Approach

First-Line Treatment

• Lifestyle modifications: Diet, exercise, and behavioral strategies focusing on weight management are the cornerstone of therapy 1, 3
• Weight loss and exercise improve all parameters of PCOS without medication side effects 4

Pharmacological Treatment

• Hormonal therapy: Oral contraceptives to reduce androgen and LH levels, improve acne and hirsutism, and induce regular menses 4
• Antiandrogens: For substantial improvement in hirsutism 4
• Insulin sensitizers: Metformin improves insulin sensitivity, increases SHBG, decreases androgen levels, and may induce ovulation 4

Monitoring and Screening

• Regular screening for cardiovascular risk factors (hypertension, dyslipidemia)
• Glucose tolerance testing and lipid profiles
• Assessment for psychological disorders 1

Special Considerations

PCOS is a lifelong condition with changing manifestations:

• Adolescence: Focus on menstrual irregularities and hyperandrogenism
• Reproductive age: Address fertility concerns
• Later life: Monitor for metabolic complications and cancer risks 5

It's important to recognize that PCOS is distinct from isolated polycystic ovaries, which can be found in 17-22% of women in the general population without the full syndrome 2.