In a double-blind, placebo controlled study, ipriflavone (600 mg/day, T.D.D.) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with the gonadotropin hormone-releasing hormone agonist (Gn-RH-A) leuproreline acetate, 3.75 mg every 30 days for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma osteocalcin levels showed a significant (P < 0.01 and P < 0.05, respectively) increase, whereas spine bone density and total body bone density significantly (P < 0.001 and P < 0.05, respectively) decreased after 3 and 6 months of GnRH-A administration. Conversely, in the ipriflavone-treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medically induced hypogonadism.