STEROIDAL DRUGS IN ENDOMETRIOSIS

Progestins, including medroxyprogesterone acetate (MPA), danazol and gestrinone, are used in the medical management of endometriosis. Danazol and gestrinone, by inducing progestin-like effects, closely resemble MPA in their actions on intrauterine endometrium. Ectopic endometrium, on the other hand, does not respond to these hormonal stimuli (as determined by estrogen and progestin receptor assays and 17β-hydroxysteroid dehydrogenase activity measurements), indicating that the therapeutic effects of steroidal drugs may not be entirely due to an action on the endometrium. At therapeutic doses, these drugs also prevent the midcycle elevation in gonadotropic hormone secretion and suppress ovarian activity (as evidenced by follicular arrest and low and stable estrogen and progesterone secretion). These indirect actions of progestins are probably more important than their direct actions on the endometrium in the treatment of endometriosis. These steroidal drugs also have androgenic effects, though the increase in the free androgen index caused by danazol is significantly larger than that induced by gestrinone or by MPA. In a study involving treatment with danazol (200 mg three times a day), high-dose MPA (100 mg/day) or placebo for 6 months, danazol and MPA were found to have equal clinical efficacy (as judged by relief of symptoms and disappearance of lesions). Danazol therapy, however, caused more androgenic and metabolic side-effects. Those patients who were infertile were also examined at 30 months. The cumulative pregnancy rate in these patients over the duration of the trial was danazol 33%, MPA 42% and placebo 46%, with no significant difference between treatments. Hormonal therapy delayed conception by approximately 8 months. Steroidal drugs of this type, which are useful in the treatment of both the lesion and symptoms of endometriosis, are not in general the treatment of choice for infertility associated with endometriosis.