Influence of vaginal danazol on uterine and brain perfusion during hormonal replacement therapy

Objective: To evaluate the effectiveness of vaginal danazol as progestin su pplement to estrogen replacement therapy, and its interference with uterine and carotid artery flow compared with medroxyprogesterone-acetate (MPA), e strogen alone, and placebo. Methods: Forty healthy women at least 12 months after natural menopause wer e randomly divided into four treatment groups: Group 1 (n=10), continuous t ransdermal estradiol (TE) (50 mug/day), plus a monthly 10-day course of MPA (10 mg/day); Group 2 (n=10), continuous TE plus a monthly 10-day course of vaginal danazol (200 mg/day); Group 3 (n=10), TE alone; Group 4 (n = 10), placebo. At baseline and during the first, third, and sixth month of treatm ent, the endometrial thickness was assessed by transvaginal ultrasonography , while the pulsatility index (PI) of the carotid and uterine arteries was assessed by color Doppler. An endometrial biopsy was also performed before and after the treatment. Results: At baseline, no significant differences between ages and other eva luated parameters were present in the four groups. In groups 1, 2, and 3, t he values of carotid and uterine PI decreased significantly and similarly d uring the treatment, while in group 4 they were unchanged. In group 3 only, the endometrium was significantly thicker during treatment than before. No endometrial hyperplasia was present in the four groups at the end of the t reatment. Conclusions: Vaginal danazol seems to be capable of counteracting the mitog enic effect of estrogen on the endometrium without reducing the effectivene ss of estrogens to improve peripheral arterial perfusion.