Uterine leiomyomatosis occurs frequently in the women population. Pharmacological treatment are suitable for this pathology, such as GnRH analogs. With these substances it has been achieved a dramatic shrinkage of leiomyomatas and uterus with a consequent rapid recovery from associated complications. However, long period of treatment, and consequent prolongated estrogen deprivation may give several problems on general physical conditions of women. In order to reduce the problems due to the lack of estrogen activity during GnRH treatment, reducing the therapy time, we add a low dose of aminogluthetimide, an aromatase inhibitor substance. A controlled study was conducted in leiomyomatosis women, to compare GnRH analog plus aminogluthetimide versus GnRH analog alone. 67 consecutive menstruated women suffering of leiomyomatosis and menometrorrhagia, referred to outpatient clinic of Ob/Gyn Department, ‘La Sapienza’ University, Roma, Italy, were enrolled in the study. Patients were randomly assigned to one of the two arms of the study. 33 patients were treated with 3.75 mg subcutaneous Goserelin every 28 days and 250 mg/daily of aminogluthetimide (group A). Thirty-four women were treated with 3.75 mg subcutaneous Goserelin every 28 days alone (group B). Serum estradiol concentration and ultrasound uterine dimension were evaluated 1 day before the beginning of therapy, after 2 months and at the end of treatment. The two groups of patients were similar for age, body mass index, serum estradiol levels and uterine volume before treatment. After 2 months of treatment in group A serum estradiol levels were 26.9 ± 3.0 pg/mL and in group B 29.4 ± 23.4 pg/mL. Uterine volume were 318 ± 43 cm2 for group A (reduction of 23.5 ± 7.9%) 369 ± 49 cm2 for group B (reduction of 12.3 ± 6.1%) (P < 0.05). The duration of the treatment in group A was 4.3 ± 0.4 months whereas in group B was 6.2 ± 0.6 months (P < 0.01). At end of treatment in group A serum estradiol levels were 21.5 ± 2.7 pg/mL and in group B 26.4 ± 3.0 pg/mL. Uterine volume were 197 ± 61 cm2 for group A (reduction of 52.6 ± 10.3%) 243 ± 51 cm2 for group B (reduction of 42.2 ± 11.4%) (P < 0.05). Combined treatment of GnRH analog and aromatase inhibitor was more effective in reducing uterine volume than GnRH analog treatment alone, also in term of time. Since serum estradiol concentration in the two group did not show significative differences, the more rapid and dramatic effect observed in combined treatment may be due to an inhibition of aromatase enzyme in the leiomyomata tissue. The combined treatment allows a sensible reduction of treatment time, reduction of hypoestrogenic period and lower costs.