Gonadotropin releasing hormone (GnRH) agonists are successfully used in the treatment of uterine leiomyomas. Different GnRH agonists may have different local effects on steroid receptors. This study was designed to evaluate potential differences in this respect between triptorelin (Decapeptyl) and goserelin (Zoladex) in a randomized controlled multicenter study using untreated patients during the luteal phase of their menstrual cycle as controls. Estrogen receptors (ERs) and progestin receptors (PRs) were measured by ligand binding assay in myoma and myometrium tissue following a 4-month treatment course with one of the GnRH analogs. In 18 untreated patients median values of ER and PR contents were comparable in myoma and myometrium: for ER at median levels of 56 and 43 fmol/mg protein, respectively; and for PR, median binding capacities were 690 and 730 fmol/mg protein, respectively. Both types of GnRH treatment (total number of patients 34) were associated with significant rises in ER in myoma (to a median level of 279 fmol/mg protein, p<0.001) and myometrium (to a median level of 109 fmol/mg protein, p<0.01). The increase in ER in myomas was significantly (p<0.001) greater than in myometria of the same patients (n=30). After treatment, PR in myomas (median level 520 fmol/mg protein) did not change significantly, but a significant (p<0.05) decrease was found for myometria (median level of 320 fmol/mg protein). Thus, ER and PR concentrations in myoma and myometrium are comparable before treatment, but estrogen suppression with GnRH analogs leads to a larger increase of ER level in leiomyomas than in myometrium, without an effect on PR, whereas myometria had lower PR levels. Therefore, leiomyoma reacts differently from myometrium towards lowered steroid concentrations in the circulation. Since the PR is considered to be a marker of estrogenic stimulation, this indicates remaining estrogenic effects on leiomyomas despite the large decrease of plasma estrogen concentrations.