Optimizing gonadotropin-releasing hormone agonist therapy in women with endometriosis

Endometriosis is a highly prevalent disease among women of reproductive age. While many treatments are available, one of the most widely utilized is treatment with gonadotropin-releasing hormone (GnRH) agonists. These agents work by producing a profound suppression of gonadotropin secretion by the pituitary, resulting in a hypoestrogenic state and subsequent diminution of endometriosis lesions. The GnRH agonists on the market have been shown to work quite well in reducing all pain symptoms associated with endometriosis, including dysmenorrhea, dyspareunia, and noncyclic pelvic pain. However, there is no evidence to suggest that this treatment is of value in endometriosis-associated infertility. Conflicting data exist regarding the role of GnRH agonists in the treatment of endometriomas, but the bulk of the evidence suggests a low degree of efficacy. GnRH agonists are often initiated with the onset of menses, but a more rapid response is observed with mid-luteal administration. A limit of 6 months per treatment course is required due to loss of bone mineral density during therapy, but this can be extended via the addition of 'add-back' therapy. Such adjunctive regimens demonstrated to maintain efficacy and reduce adverse effects include progestogen alone or a low-dose combination of estrogen and progestogen. Retreatment with these drugs is supported by limited data. The use of GnRH agonists as surgical adjuncts has been studied by several investigators. Their use preoperatively has not been shown to be of value. Similarly, 3 months of postoperative administration has failed to enhance treatment. However, 6 months of postoperative GnRH agonists appear to improve the duration of relief of pain symptoms. Future studies will need to focus on the role of these agents when used for repeated courses, in young women, and in conjunction with assisted reproduction.