Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up

To assess post-treatment effects in endometriosis patients of a 12-month course of GnRH agonist alone or with one of three "add-back" regimens.

This is a post-treatment follow-up analysis of a randomized, double-masked, placebo-controlled 52-week trial. All patients had received monthly leuprolide acetate and were randomized to one of four groups: A-daily placebo; B-daily norethindrone acetate 5 mg; C-daily norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg; and D-daily norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg. Of 201 patients enrolled in the initial trial, 123 completed at least 280 days of therapy and entered the follow-up period. Physical findings and symptoms were quantified, and lumbar spine bone mineral density was determined at intervals for up to 12 and 24 months post-therapy.

Symptom and pelvic examination scores remained significantly below baseline for at least 8 months after completion of therapy for all four groups (P <.05). Findings were not affected by endometriosis scores noted on screening laparoscopy. Mean bone mineral density values remained at or above baseline in all add-back groups. The significant mean loss in bone density in group A during therapy reversed slowly and had not returned to baseline at the final follow-up visit (P <.001).

GnRH agonist and norethindrone acetate alone or combined with low-dose conjugated equine estrogens administered to symptomatic endometriosis patients for 12 months provides extended pain relief and bone mineral density preservation after completion of therapy.