This is the second published case report of Lleuprolide acetate for depot suspension (LD)-induced mania. Both reports detail a patient with a prior psychiatric history of both depressive and hypomanic episodes. While depression is a predictable and documented side effect of LD and menopause (especially in those with a previous history of symptoms), manic reactions are rare and unexplained. Possible causative mechanisms behind the LD-induced manic episodes are discussed, and we suggest that patients with a single previous hypomanic episode are at risk for LD-induced mania.