Impact of different GnRH analogs in benign gynecological disorders related to their chemical structure, delivery systems and dose

This review addresses the question of whether the different gonadotropin releasing hormone (GnRH) agonists in clinical use might have different impacts, related to their chemical structure, delivery system and dose. Impact was investigated in benign gynecological disorders, i.e. endo-metriosis and leiomyoma. Arguments are presented indicating that a difference in impact of different analogs can be expected.All currently used intranasal, daily subcutaneous and depot preparations finally give rise to low levels of serum estradiol. The number of days before the first ovulatory menstruation after discontinuation of GnRH agonist treatment is remarkably constant. Four weeks after the last impact of the agonist, there is resumption of follicle growth. This phenomenon is independent of chemical structure, delivery system and dose. One should realize, however, that it generally takes about 30 days before the impact of a depot preparation disappears. Consequently, the impact of a depot preparation lasts 4 weeks longer than that of an otherwise applied agonist. Thus resumption of pituitary activity after discontinuation of a depot formulation takes 4 weeks longer than after discontinuation of non-depot formulations.All agonists have an impressive effect on endometriosis, independent of their chemical structure and delivery system. However, there are no studies comparing different agonists with the same delivery system in comparable endometriosis groups. Similarly, all agonists considerably reduce myoma volume, independently of their chemical structure and delivery system. Again, there are no studies comparing different agonists with the same delivery system in comparable myoma groups. Bone loss has been reported in long-term treatment with agonists, but is reversible when the agonists are given for no longer than 6 months. Again, there are no studies on bone mineral density comparing the effect of different agonists with the same delivery systems. It appears that the dose of the agonists in depot form can be lowered by at least 50%, while the clinical impact on estradiol, follicle stimulating hormone, luteinizing hormone and myomas remains the same. These data are consistent with an ‘all or nothing’ law for the impact of the agonists.It is concluded that carefully designed studies are needed to establish the minimal effective dose of agonists per kilogram body weight, providing maximal efficacy with minimal side-effects.