Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis.

Abstract

Danazol is routinely administered orally to inhibit ovulation and to treat pelvic endometriosis. However, recent evidence suggests that danazol can act directly on endometriotic tissue in vitro to inhibit DNA synthesis and induce apoptosis. Danazol was administered via the vagina in this study, using a vaginal ring drug delivery system containing 1500 mg of danazol. This therapy was effective for treatment of pelvic endometriosis, especially for deeply infiltrating endometriosis, resulting in a cure of dysmenorrhoea and tenderness in the cul-de-sac within 3 months, and of induration or nodularity in the cul-de-sac within 7 months. Moreover, conception was possible during insertion of the vaginal ring in 17 out of 31 infertile women with deeply infiltrating endometriosis, and in two out of eight infertile women with ovarian endometriotic cysts not adhering to the cul-de-sac and without deeply infiltrating endometriosis. Serum danazol concentrations, high during oral daily 400 mg danazol therapy, but undetectable during vaginal danazol ring therapy, explain why ovulation and conception could occur during insertion of the vaginal danazol ring, and why general side-effects, which are often observed during oral danazol therapy, were not observed during vaginal danazol ring therapy. Danazol seems to be absorbed through the vaginal mucosa and reaches the deeply infiltrating endometriosis via diffusion.