Influence of vaginal danazol on uterine and brain perfusion during hormonal replacement therapy.
OBJECTIVE
To evaluate the effectiveness of vaginal danazol as progestin supplement to estrogen replacement therapy, and its interference with uterine and carotid artery flow compared with medroxyprogesterone-acetate (MPA), estrogen alone, and placebo.


METHODS
Forty healthy women at least 12 months after natural menopause were randomly divided into four treatment groups: Group 1 (n=10), continuous transdermal estradiol (TE) (50 microg/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 treatment, 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 evaluated parameters were present in the four groups. In groups 1, 2, and 3, the values of carotid and uterine PI decreased significantly and similarly during 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 treatment.


CONCLUSIONS
Vaginal danazol seems to be capable of counteracting the mitogenic effect of estrogen on the endometrium without reducing the effectiveness of estrogens to improve peripheral arterial perfusion.
Guerriero
S
S
Department of Obstetrics and Gynaecology, University of Cagliari, Cagliari, Italy. gimeli@tin.it
Paoletti
A M
AM
Ajossa
S
S
Vacca
A M
AM
Pilia
I
I
Orru'
M
M
Perrone
G
G
Melis
G B
GB
D000282:Administration, Intravaginal; D001783:Blood Flow Velocity / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D002343:Carotid Artery, Internal / Q000187:drug effects / Q000502:physiology*; D003613:Danazol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008593:Menopause; D008875:Middle Aged; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D011673:Pulsatile Flow / Q000187:drug effects*; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects
D045167:Progesterone Congeners; D003613:Danazol