Phase 2 bupropion XL norepinephrine–dopamine reuptake inhibitor to improve AI tolerance (HSDD)

University of Illinois at Chicago is running this Phase 2 supportive-care study in women with resected, early-stage hormone receptor–positive breast cancer taking adjuvant aromatase inhibitor (AI) therapy who develop hypoactive sexual desire disorder (HSDD). Participants continue standard endocrine therapy (AI ± ovarian suppression with a GnRH agonist for premenopausal patients), with a protocol-directed switch to a different AI if HSDD is present at baseline (e.g., non-steroidal to steroidal AI or vice versa), and an option to add bupropion XL. Bupropion XL (commonly marketed as Wellbutrin XL; multiple generics) is a norepinephrine–dopamine reuptake inhibitor used for depression and smoking cessation, repurposed here to test whether it improves patient-reported sexual functioning while maintaining adherence to curative-intent endocrine therapy. The commercial/scientific angle is pragmatic: sexual side effects are a common reason patients struggle with long-duration AI therapy, and improving tolerability could indirectly protect cancer outcomes by supporting persistence. Today’s care after surgery is 5–10 years of endocrine therapy (AI for postmenopausal patients; ovarian suppression + AI is common for higher-risk premenopausal disease), with symptom management that often includes nonhormonal strategies and selective use of vaginal therapies; this trial evaluates a non-estrogen systemic option aimed at sexual desire specifically.