The effect of sorafenib in postoperative adhesion formation in a rat uterine horn model.

OBJECTIVE: Postoperative adhesions are a serious problem. In this study, we aimed to observe the effects of sorafenib in postoperative adhesions and, to examine the effects of sorafenib on tissue levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). MATERIAL AND METHODS: Twenty female Wistar albino rats were randomized into two equal groups; sorafenib group (sorafenib treated) and control group; then all rats underwent laparotomy. Adhesions were developed by scalping on the anti-mesenteric surfaces of the right uterine horns. After 14 days, adhesions were investigated by using macroscopic, histopathological and immunohistochemical (for VEGF and PDGF) methods. RESULTS: The sorafenib group had lower scores of total adhesions [1 (0-2.5) vs 1.5 (1-4); p: 0.037], staining of VEGF [1 (0-1) vs 1 (1-3); p: 0.029] and PDGF [1 (0-2) vs 2 (1-3); p: 0.006], and vascular proliferation [1 (0-2) vs 2 (1-3); p: 0.038] than the control group. CONCLUSION: The findings of the present study show that sorafenib, a tyrosine kinase inhibitor, significantly reduced postoperative adhesion formation. This effect may be explained by inhibition of VEGF, PDGF, and thus vascular proliferation.

Clinical efficacy of lower dose flutamide 125 mg/day in the treatment of hirsutism.

Thirty-four patients with moderate-severe hirsutism were enrolled in this study. The patients received 125 mg/day flutamide for a period of 6 months. Hirsutism score and hormone parameters including FSH, LH, T, free T, androstenedione (A), DHEAS, PRL and sex hormone-binding globulin (SHBG) levels were evaluated in all patients before treatment and repeated at every three-monthly intervals. Hirsutism greatly improved during flutamide therapy, and the hirsutism score significantly decreased at month 3 and 6 from a mean (+/-SD) of 17.19+/-4.55 to 10.75+/-3.84 (p<0.001) and 17.19+/-4.55 to 5.91+/-2.53 (p<0.001), respectively. A significant reduction in hirsutism score (mean%+/-SD) as compared to baseline was observed at 3 months (37.78+/-13.30, p<0.001) and at 6 months (65.47+/-13.49, p<0.001). No significant changes in the levels of hormone and no serious side effects were observed in the patients. The lower dose flutamide, 125 mg/day, is a safe and cost-effective drug in the treatment of hirsutism. Lower dose flutamide may be used in place of high dose flutamide, 250 to 750 mg/day.

The efficacy of 250 mg/day flutamide in the treatment of patients with hirsutism.

OBJECTIVE: To investigate the effects of low dose flutamide (250 mg/d) on hirsutism score and hormone levels in women with hirsutism. DESIGN: Nonrandomized, prospective clinical trial. PATIENTS: Forty-one patients with moderate-severe hirsutism were included in the study. INTERVENTION: Hirsute patients received 250 mg/d flutamide for a period of 6 months. MAIN OUTCOME MEASURES: Hirsutism score, FSH, LH, E2, total T, free T, androstenedione, DHEAS, PRL, 17-hydroxyprogesterone, and sex hormone-binding globulin levels were detected in all the patients before treatment and every 3 months during treatment. RESULTS: Treatment with the antiandrogen flutamide resulted in a particularly rapid and marked decrease in the hirsutism score, which decreased from 17.48 +/- 5.35 to 5.07 +/- 2.89 after 6 months. No significant changes in the levels of hormone and no serious side effects were observed in the study. CONCLUSION: The low-dose flutamide, 250 mg/d, is a cost-effective drug in the treatment of hirsutism. Low-dose flutamide may be used in place of high-dose flutamide, 500 to 750 mg/d.