GnRH Agonists

GnRH agonists are a class of synthetic peptide drugs (triptorelin, goserelin, buserelin), which are structural analogs of the natural hypothalamic gonadotropin-releasing hormone, but possess higher receptor affinity and resistance to enzymatic degradation.

Etiology and pathophysiology

Under physiological conditions, GnRH is secreted by the hypothalamus in a pulsatile manner (every 90 minutes), which stimulates the pituitary to release FSH and LH. Depo-forms of agonists introduce a constant high concentration of the hormone in the blood. This implements a two-phase mechanism of action:

1. Stimulation Phase (flare-up): In the first 3–7 days, there is a transient release of gonadotropins and estradiol.
2. Desensitization Phase (down-regulation): After 10–14 days, pituitary receptors lose sensitivity and “internalize” within the cell. Secretion of FSH and LH is blocked, the ovaries cease to function, and estradiol levels fall to castration levels (reversible medical menopause).

Clinical significance

GnRH agonists are the most potent therapy for hormone-dependent diseases. Profound hypoestrogenism induces atrophy of endometriosis foci, alleviates pelvic pain, and reduces the volume of the uterus and leiomyoma nodes by 30-50%. Used in IVF protocols to prevent premature ovulation. Monotherapy duration is limited to 6 months due to the risk of osteoporosis.