Pathophysiology
Clinical meaning
The HPO axis controls the menstrual cycle through coordinated hormonal signalling. The hypothalamus releases GnRH in pulsatile fashion (every 60-90 minutes), stimulating anterior pituitary gonadotrophs to secrete FSH and LH. GnRH pulse frequency determines gonadotropin ratio: slower frequency favours FSH secretion (follicular phase), while faster frequency favours LH (luteal phase). In the follicular phase, FSH recruits a cohort of ovarian follicles; the dominant follicle produces rising estradiol which initially suppresses FSH (negative feedback) and then, at a sustained threshold of approximately 200 pg/mL for 48 hours, triggers the LH surge (positive feedback) causing ovulation. After ovulation, the corpus luteum produces progesterone and estradiol, supporting the secretory endometrium. If implantation does not occur, corpus luteum regression causes progesterone withdrawal, triggering menstruation. This elegant feedback system is disrupted in conditions such as hypothalamic amenorrhea, PCOS, and premature ovarian insufficiency.