Polycystic Ovary Syndrome (PCOS) Quiz

Overview

• Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age.
• It is a leading cause of infertility and pregnancy complications.
• Associated with insulin resistance, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease, and increased risk of developing type 2 diabetes.

Theory

• Epidemiology: PCOS affects about 6% of women of reproductive age in the US and Europe using the 1990 National Institutes of Health criteria.
• Prevalence rates vary depending on the criteria used, with rates ranging from 10% to 20% of women.
• No prospective studies have documented incidence rates for PCOS.
• PCOS accounts for 80% to 90% of cases of hyper-androgenism in women.
• Aetiology: The exact cause of PCOS is unknown, but it is likely to be a complex disorder involving multiple genes.
• Genetic factors: Heritability of PCOS is estimated to be around 70%, suggesting that most PCOS risk depends on genetic factors.
• Susceptibility genes: Several genes have been identified as risk factors for PCOS, including DENND1A, THADA, and LHCGR.

Pathophysiology

• The pathophysiology of PCOS is not well understood, but it is thought to involve interactions between the ovary, adrenal, hypothalamus, pituitary, and insulin-sensitive tissues.
• Insulin resistance leads to compensatory hyperinsulinaemia, which promotes ovarian androgen output and may also promote adrenal androgen output.
• High insulin levels also suppress hepatic production of sex hormone-binding globulin, exacerbating hyper-androgenaemia.
• LH excess is also thought to contribute to ovarian androgen output.

Classification

• There is no formal classification system for PCOS, but a proposed classification system includes:
  • Mild PCOS: characterised by irregular periods, polycystic ovaries on ultrasound, mildly elevated androgen concentrations, and normal insulin concentrations.
  • Ovulatory PCOS: characterised by normal periods, polycystic ovaries on ultrasound, elevated androgen concentrations, and increased insulin concentrations.
  • Hyper-androgenism and chronic anovulation: characterised by irregular periods, normal ovaries on ultrasound, elevated androgen concentrations, and increased insulin concentrations.
  • Severe PCOS: characterised by irregular periods, polycystic ovaries on ultrasound, elevated androgen concentrations, and increased insulin concentrations.

Diagnosis

• Approach: Diagnosis of PCOS is largely a diagnosis of exclusion, and there are no pathognomonic features.
• History: Common features include hirsutism, acne, and scalp hair loss, as well as irregular and infrequent periods.
• Investigations: The diagnosis of PCOS can be made when infrequent/reduced menstrual bleeding also exists, and polycystic ovarian morphology is documented on ultrasound.
• Ultrasound: Polycystic ovaries are present in 75% of women with PCOS, but are also seen in up to 25% of normal women and women with other endocrinopathies.
• Serum anti-Mullerian hormone (AMH) levels: May be used as a diagnostic tool, but optimal cut-off values have not been defined.### Diagnosis of Polycystic Ovary Syndrome (PCOS)

Key Diagnostic Factors

• Presence of risk factors:
  • Family history of PCOS
  • Premature adrenarche
  • Female of reproductive age
• Symptoms:
  • Irregular menstruation (75% of women with PCOS)
  • Infertility (common)
  • Hirsutism (60% of women with PCOS)
  • Acne (15% to 25% of women with PCOS)
  • Overweight or obesity (30% to 80% of women with PCOS)
  • Hypertension (common)
  • Scalp hair loss (uncommon)
  • Oily skin or excessive sweating (uncommon)
  • Acanthosis nigricans (uncommon)

Investigations

• 1st test to order:
  • Serum 17-hydroxyprogesterone (to exclude 21-hydroxylase-deficient non-classic adrenal hyperplasia)
  • Serum prolactin (to exclude hyperprolactinaemia)
  • Serum thyroid-stimulating hormone (to exclude thyroid dysfunction)
  • Oral glucose tolerance test (to evaluate metabolic risk factors)

Laboratory Tests

• Biochemical hyper-androgenism:
  • Calculated free testosterone, free androgen index, calculated bioavailable testosterone, or high-quality testosterone assays (e.g. liquid chromatography tandem mass spectrometry)
  • Dehydroepiandrosterone sulfate (DHEAS) levels may be checked if other androgens are normal
• Insulin resistance:
  • Fasting insulin levels >69 to 104 pmol/L (10-15 micro-units/mL) may suggest insulin resistance
  • Peak insulin levels during oral glucose tolerance test:
    • 695-1042 pmol/L (100-150 micro-units/mL) may indicate mild insulin resistance
    • 1042-2084 pmol/L (150-300 micro-units/mL) may indicate moderate insulin resistance
    • >2084 pmol/L (300 micro-units/mL) may indicate severe insulin resistance

Ultrasound

• Polycystic ovarian morphology allows a diagnosis of PCOS to be made (Rotterdam criteria only)

Additional Tests

• Androstenedione measurement may increase the number of women identified as hyper-androgenaemic by 10%
• Checking DHEAS is of little value except in cases of rapid virilization

Metabolic Risk Factors

• Prevalence of abnormal glucose tolerance (impaired fasting glucose, impaired glucose tolerance, or diabetes) is as high as 40% in PCOS

• Odds of prevalent impaired glucose tolerance was 3.3, and of prevalent diabetes 2.9, in PCOS### Diagnosis of Diabetes

• Diabetes is defined as a fasting glucose level of ≥7 mmol/L (≥126 mg/dL) or a 2-hour glucose level of ≥11 mmol/L (≥200 mg/dL).

• All women should be screened for impaired glucose tolerance with an oral glucose tolerance test.

• Those with normal glucose tolerance should be re-screened at least every 2 years.

• Those with impaired glucose tolerance should be screened annually for type 2 diabetes.

Diagnosis of Polycystic Ovary Syndrome (PCOS)

• Dyslipidaemia is often observed in PCOS, and assessment of fasting lipids has been advocated for all women with PCOS.
• Other tests to consider for diagnosing PCOS include:
  • Serum total and free testosterone (elevated levels suggest hyper-androgenaemia)
  • Serum dehydroepiandrosterone sulfate (DHEAS) (elevated levels suggest hyper-androgenaemia)
  • Serum androstenedione (elevated levels suggest hyper-androgenaemia)
  • Pelvic ultrasound (presence of ≥20 follicles in each ovary measuring 2-9 mm in diameter and/or increased ovarian volume)
  • Serum anti-Mullerian hormone (elevated levels may indicate PCOS)
• Basal body temperature monitoring may indicate ovulation or anovulation.
• Luteal phase progesterone measurement may indicate ovulation or anovulation.

Differentials for PCOS

• 21-hydroxylase deficiency (partial deficiency of the 21-hydroxylase enzyme within the cortisol biosynthetic precursors) may present with similar symptoms to PCOS.
• Other differentials to consider include congenital adrenal hyperplasia and non-classic congenital adrenal hyperplasia.

Management of PCOS

• Treatment for PCOS may involve adding metformin to clomifene to improve ovulation rates.
• Injectable treatments such as gonadotrophins may be used if other measures fail.
• Gonadotrophins directly act on the ovary, stimulating follicular recruitment and maturation.
• Risks of treatment with gonadotrophins include multiple pregnancies and ovarian hyperstimulation syndrome (OHSS).