The Effects of Gonadotropin-Releasing Hormone Agonist Combined with Add-Back Therapy on Quality of Life for Adolescents with Endometriosis: A Randomized Controlled Trial

Study Objective

Use of gonadotropin-releasing hormone agonists (GnRHa) to treat endometriosis can cause mood and vasomotor side effects. “Add-back therapy,” the combination of low-dose hormones, limits side effects but research is limited to adults. We sought to characterize quality of life (QOL) before treatment and to compare an add-back regimen of norethindrone acetate (NA) with conjugated estrogens (CEE) to NA alone for preventing side effects of GnRHa therapy in female adolescents with endometriosis.

Design

Twelve-month double-blind, placebo-controlled trial.

Setting

Pediatric Gynecology clinic in Boston, Massachusetts.

Participants

Fifty female adolescents (aged 15-22 years) with surgically confirmed endometriosis initiating treatment with GnRHa.

Interventions

Subjects were randomized to: NA (5 mg/d) with CEE (0.625 mg/d) or NA (5 mg/d) with placebo. All subjects received leuprolide acetate depot every 3 months.

Main Outcome Measures

The Short Form-36 v2 Health Survey, Beck Depression Inventory II, and Menopause Rating Scale were completed at repeated intervals.

Results

At baseline, subjects reported impaired physical health-related QOL compared with national norms (all P < .0001). Over 12 months, these Short Form-36 v2 scores improved (all P < .05). Subjects receiving NA with CEE showed greater improvements in the pain, vitality, and physical health subscales (P_{between groups} < .05) than those receiving NA alone, as well as better physical functioning (P < .05). There were no changes in depression or menopause-like symptoms in either group.

Conclusion

Female adolescents with endometriosis initiating GnRHa therapy have impaired QOL. Treatment with GnRHa combined with add-back therapy led to improved QOL, with no worsening of mood or menopausal side effects. NA with CEE was superior to NA alone for improving physical health-related QOL.