Polycystic Ovarian Syndrome

Background

• Complex endocrine disorder characterised by excess androgen, metabolic syndrome and multiple cysts in the ovary (amongst other features)
• PCOS is common
  • polycystic ovaries occur in up to a third of women of reproductive age
  • 5-7% have features of PCOS

Causes/Pathophysiology

• Unknown- multifactorial (genetic and environmental)
• Theca cells produce excess androgens (may be due to hyperinsulinaemia or increased GnRH pulsations with increased LH levels)
  • Decreased peripheral insulin sensitivity (insulin resistance) and consequent hyperinsulinaemia may be a key process in some but not all women
  • Excess adrogen stops follicular development and ovulation/menstrual cycle
  • Insulin also inhibits the hepatic production of sex binding globulin so there is more free androgen circulating in the blood
  • Increased LH also causes a relative increase in androgen production
  • NB Patients with PCOS tend also to have high oestrogen levels (testosterone converted to oestrogen and less oestrogen is opposed by follicular progesterone so can cause hyperplasia of the endometrium and associated cancer risk)

Presentation

• Suspect PCOS in women with
  • Oligo-/amenorrhoea (oligo-/anovulation) or infertility
  • Features of hyperandrogenism e.g. hirsutism, acne vulgaris after adolescence or male pattern alopecia
  • There may also be psychological features e.g. mood swings, depression, anxiety etc
• Often women also have features of the metabolic syndrome e.g.
  • Obesity (often central)
    • Sleep apnoea
  • Acanthosis nigricans
• There can be a family history

Diagnosis

• Two out of
  • Oligo-anovulation or anovulation
  • Clinical and/or biochemical signs of hyperandrogenism
  • Polycystic ovaries (12 or more follicles measuring 2-9mm in diamete in one or both ovaries and/or increased ovarian volume (>10ml))

Investigations

• Pregnancy test (amenorrhoea)
• Total testosterone (often elevated (>5nmol/l (norm 0.5-3.5nmol/l)))
  • If considerably elevated, consider also congenital adrenal hyperplasia, Cushing’s, or an androgen secreting tumour
• Sex-hormone binding globulin (low)
• => Free Androgen Index
  • (testosterone/SBG)- often high in PCOS
• Also measure LH/FSH (to rule out premature ovarian failure (increased) or hypogonadotrophic hypogonadism (low))
  • Prolactin (may be mildly elevated)
  • TSH/T4
• NB Oestrogen levels not routine
• Ovary USS (unless the diagnosis has already been made)

Management

• First line treatment is the COCP (or other hormonal contraceptive)- particularly for menstrual irregularity, symptoms of hirsutism, and acne
  • It may be sensible to induce a bleed with progestogen (medrocyprogesterone- provera) every 3-4 months to reduce the risk of hyperplasia
• Advise on lifestyle and weight management where possible/appropriate for weight management and diabetes/IGT
• Metformin can also be used first line (particularly in women wanting to conceive) for cutaneous manifestations (2nd line for weight management/diabetes/IGT after lifestyle and 2nd line for menstrual irregularity after OCT
  • DO NOT USE TZDs for diabetes/insulin resistance
• For treatment of infertility, clomiphene citrate (+ metformin) is recommended