Extending the treatment boundaries: Zoladex and add-back

OBJECTIVE: To review the evidence that add-back hormone replacement therapy (HRT) can ameliorate the metabolic consequences of gonadotropin-releasing hormone (GnRH) agonist treatment in women with symptomatic endometriosis. METHODS: A review of relevant literature. RESULTS: Early studies suggested that add-back HRT maintained bone mineral density (BMD) without reducing the symptomatic benefit of GnRH treatment. Both high-dose progestogen and low dose progestogen plus cyclical etidronate are effective in maintaining BMD. Standard and low dose HRT add-back may be more effective in relieving the hypo-estrogenic side-effects of GnRH agonist therapy. Randomized controlled studies have shown that both low-dose and standard-dose add-back HRT reduce the side-effects of GnRH agonist therapy, and that this benefit extends to 12 months of treatment. CONCLUSIONS: GnRH agonist treatment with add-back HRT seems to offer the hope of improved treatment for women with endometriosis, but the optimum treatment duration and time to start HRT have yet to be defined.