GnRH agonists are derived from the native molecule by substitution of a D-amino acid in position 6 which increases their resistance to enzymatic breakdown and their affinity for LH-RH receptors in comparison with the native hormone. Because of this improved resistance which increases their half-life they have a super-agonistic effect. In 1973, two years only after he characterized LH-RH, A.V. Schally synthesized several GnRH analogs, including D-TRP6-LHRH obtained by substituting the glycine-6 with a D-tryptophan. The biological half life of this agonist injected by the subcutaneous route is 10 times greater than that observed after intravenous injection because of the progressive release of the peptide from the injection site. Pharmaceutical research has led to the development of delayed-release formulations allowing doses to be spaced by intervals of several weeks, or even three months when needed in some indications (Decapeptyl slow release). Triptorelin, as the other GnRH agonists, strongly reduces LH secretion, by preventing the production of the LH-beta subunit. On the opposite, the production of LH-alpha subunit is markedly increased and remains responsive to exogenous GnRH injection, demonstrating that the agonist does not induce actual pituitary desensitization. Compared with LH-RH antagonists which inhibit both LH-alpha and LH-beta subunit secretion, agonists offer the advantage of a sustained efficacy even after one or two days of withdrawal, while the effect of the agonist disappeared as soon as the administration is stopped. On the other hand, GnRH antagonists do not induce the initial hyperstimulation of the gonadotrophs, the so-called flare up, characteristic of the superagonistic effect.