Aim of the study is to compare the effects of preoperative therapy with tibolone plus gonadotropin-releasing hormone analogue (GnRH-a) in premenopausal women with those of GnRH-a alone on clinical response, uterine volume, immunohistochemical expression of platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and vascular features of myomas. Seventy women with symptomatic uterine fibromatosis were treated for four months with leuprorelin acetate alone or plus tibolone. Untreated patients were submitted to uterine surgery directly. Uterine volume, hematological data, BMD, myoma-related symptoms and hot flushes were evaluated at the admission and before surgery. Immunohistochemical expression of PDGF, bFGF and VEGF, vascular changes and CD105 expression, as a marker of angiogenesis, were evaluated in myomas obtained after surgery. Uterine volume and myoma-related symptoms reduced and hematological variables increased in treated patients. BMD decreased in patients treated with GnRH-a alone. Hot flushes were less in GnRH-a plus tibolone group than in GnRH-a group. Immunohistochemical expression of PDGF, bFGF and VEGF, vascularization and angiogenesis reduced in treated patients in comparison with untreated ones. In conclusion, the administration of tibolone plus GnRH-a before uterine surgery does not change the clinical and immunohistochemical effects of GnRH-a alone.