A risk benefit assessment of drugs used in the treatment of endometriosis.

Medical treatments of endometriosis rely upon the hormonal dependence of endometriotic implants for further growth and extension. The cyclic nature of the symptoms means they may be helped by agents that suppress menstruation both from the endometrium and within the endometriotic lesions. In comparative trials, progestogens have been shown to achieve a similar reduction in symptoms and to induce regression of deposits, but to date there are few long term follow-up data concerning gestrinone. The recent introduction of gonadotrophin-releasing hormone (GnRH) agonists, highly effective at inducing a state of sustained hypoestrogenaemia, is providing another group of compounds suitable for use in the treatment of endometriosis. In comparative trials with danazol, a number of these compounds administered in novel formulations (as intranasal sprays or sustained release depots), have been shown to significantly reduce symptoms both during treatment and for 6 to 12 months post-treatment when compared with baseline. In addition, there are highly significant reductions in revised American Fertility Society (R-AFS) total and implant alone scores following 6 months' therapy. Whilst these changes are not significantly different from danazol, there are fewer patients discontinuing treatment with GnRH agonists than with danazol. The low circulating levels of 17 beta-estradiol seen during GnRH analogue therapy result in alterations of bone mineral metabolism similar to those observed at the menopause. Continued prolonged use would thus result in reduced bone mass and this factor will limit the duration of use of GnRH agonists long term until appropriate combination ('add-back') regimens to protect bone are developed.