HPG Axis (Hypothalamic-Pituitary-Gonadal Axis)
The hormonal system linking the hypothalamus, pituitary, and gonads that controls reproductive function and sex hormone production. The HPG axis is the primary target of GnRH agonists and antagonists used to treat prostate cancer, endometriosis, precocious puberty, and infertility.
Technical Context
The HPG axis requires pulsatile GnRH release (approximately every 60-90 minutes) from hypothalamic neurons to maintain normal gonadotropin secretion. Pulse frequency modulates the LH:FSH ratio — faster pulses favour LH, slower pulses favour FSH. This pulsatility dependence is therapeutically exploited: continuous GnRH (from depot/implant formulations) disrupts pulsatile signalling → desensitisation → downregulation → suppression of LH, FSH, and sex steroids. GnRH antagonists achieve the same endpoint (gonadotropin suppression) through direct receptor blockade, but without the initial flare phase. The HPG axis is the target for prostate cancer (testosterone suppression), endometriosis/fibroids (oestrogen suppression), precocious puberty (halting premature activation), and IVF (controlled ovarian stimulation).