The role of GnRH agonists plus add-back therapy in the treatment of endometriosis

Agonistic analogs of GnRH have emerged as effective drugs in the treatment of pelvic pain associated with endometriosis. Iatrogenic hypoestrogenism is the fundamental mechanism through which GnRH agonists induce regression of the exquisitely estrogen-dependent endometriotic lesions. The decrease in bone mass consistently observed in women on long-term GnRH agonist treatment has prompted regulatory agencies such as the FDA to approve the use of these drugs for a maximum of six months in the treatment of endometriosis. The very high recurrence rate of pelvic symptomatology after the interruption of medical therapy underlines the importance of strategies aiming at improving the safety of effective long-term treatments. Data has recently become available suggesting the existence of an ideal range of circulating estradiol levels which would maintain a normal bone metabolism and still cause atrophy of endometriotic lesions. Add-back regimens including estrogen preparations have been therefore studied with variable results. In strict analogy, as oral progestins have been shown to improve bone mass in postmenopausal women, regimens employing progestin add-back have been proposed. Our review describes most of the currently published studies employing these and other substances in association with the commonly used GnRH agonists in patients with symptomatic endometriosis.