Expansion
Insulin resistance drives ovarian androgen production and disrupts ovulation
Expansion
Mechanism
- Insulin resistance with compensatory hyperinsulinaemia
- Insulin acts on ovarian theca cells to increase androgen production
- Insulin suppresses hepatic sex hormone binding globulin, so the free androgen fraction rises further
- Raised LH to FSH ratio with increased GnRH pulse frequency
- Follicles arrest before ovulation, giving multiple small follicles and anovulation
- Anovulation means unopposed oestrogen, with no progesterone from a corpus luteum
Rotterdam criteria require two of three: oligo- or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound.
Consequences follow the mechanism: hirsutism and acne from androgens; irregular cycles and subfertility from anovulation; and endometrial hyperplasia and carcinoma risk from unopposed oestrogen, which is why cyclical progestogen or the combined pill is given.
Metabolic risk is substantial: impaired glucose tolerance, type 2 diabetes, dyslipidaemia and non-alcoholic fatty liver. Weight loss improves every aspect, and metformin addresses the underlying resistance.