Pathophysiology
Clinical meaning
The menstrual cycle is a precisely coordinated neuroendocrine process governed by the hypothalamic-pituitary-ovarian (HPO) axis through pulsatile gonadotropin-releasing hormone (GnRH) secretion, pituitary gonadotropin release, and ovarian steroid feedback. The GnRH pulse generator in the arcuate nucleus of the hypothalamus must fire in a pulsatile pattern (every 60-90 minutes in the follicular phase, every 2-4 hours in the luteal phase) for normal gonadotropin secretion โ continuous GnRH paradoxically downregulates pituitary GnRH receptors and suppresses FSH/LH (the pharmacologic basis of GnRH agonist therapy). The follicular phase begins with rising FSH stimulating a cohort of antral follicles; FSH induces aromatase expression in granulosa cells, converting thecal androgens to estradiol. By day 5-7, the dominant follicle emerges through its greater FSH receptor density and local autocrine/paracrine factors (activin, inhibin B, IGF-1), while non-dominant follicles undergo atresia as declining FSH falls below their survival threshold. Rising estradiol from the dominant follicle initially exerts negative feedback on pituitary FSH and LH; however, when estradiol exceeds approximately 200 pg/mL for 36-48 hours, feedback switches from negative to positive, triggering the mid-cycle LH surge that initiates ovulation approximately...