GnRH

Where it comes from

Made in

Some ten thousand neurons scattered through the preoptic area, hypothalamus and beyond (the familiar “thousand” is the mouse’s count), which migrated there from the nose before birth

Sent out by

In pulses every one to two hours, driven by kisspeptin; the pulse rate sets LH versus FSH

Acts on

• Pituitary gonadotrophs (LH and FSH)

What it does

• Starts puberty when its pulses resume and keeps cycles and sperm production going
• Continuous exposure desensitises the receptor and switches the axis off, the trick the medicines use ⁴
• Its neurons’ failure to migrate causes Kallmann syndrome, hypogonadism with no sense of smell

In medicine

• GnRH agonists (leuprolide, goserelin, triptorelin) shut off sex hormones for prostate cancer, endometriosis, fibroids, precocious puberty, IVF and gender-affirming care
• GnRH antagonists do it without the initial surge: cetrorelix and ganirelix in IVF, degarelix and relugolix in prostate cancer, and the tablets elagolix, relugolix and linzagolix for endometriosis and fibroids ²
• Pulsatile gonadorelin by pump restores ovulation and fertility in hypothalamic amenorrhoea and Kallmann syndrome

Beyond the body’s own use

• Agonist and antagonist were compared head to head in 930 men with prostate cancer: oral relugolix held castration in 96.7 per cent against 88.8 per cent for leuprolide, and major cardiovascular events were 2.9 against 6.2 per cent ¹
• GnRH and its agonist analogues are banned in sport in male athletes, where a course raises testosterone before it suppresses it; LH and chorionic gonadotropin sit in the same part of the Prohibited List ³
• Long courses lower bone density, which is why add-back oestrogen and progestogen are given alongside the tablets used for endometriosis and fibroids
• Its analogues are not traded outside medicine; they are injections and implants given under specialist care, and the peptide itself is destroyed in the gut