Combination Treatment with Bromocriptine and Metformin in Patients with Bromocriptine-Resistant Prolactinomas: Pilot Study

BACKGROUND: Prolactinomas are the most common functional pituitary adenomas and dopamine agonists are the primary therapy. However, some patients are resistant to dopamine agonists. Recently, metformin has been proposed as a cancer treatment. CASE DESCRIPTION: This study is a retrospective review of 2 cases including 1 patient with prolactinoma who was resistant to bromocriptine, diagnosed with impaired glucose tolerance, and administered metformin. Surprisingly, combining the patient's treatment with metformin decreased prolactin (PRL) levels to 12 ng/mL and significantly decreased the size of the tumor after 1 year of combination therapy. As menstruation resumed and galactorrhea resolved, the patient became pregnant and stopped using metformin but continued taking bromocriptine. She gave birth to a healthy boy in August 2016. After delivery, she decided to breastfeed the baby and only took bromocriptine. After 14 months of using bromocriptine alone, her PRL level increased to 208 ng/mL and the tumor reappeared (7 mm 3 8 mm 3 9 mm). Interestingly, the patient's PRL level decreased from 208 ng/mL to 150 ng/mL 2 months after using combination treatment with bromocriptine and metformin. On the basis of these findings, a second bromocriptine-resistant patient was recruited. After 3 months of combined treatment with bromocriptine and metformin, the patient's PRL level decreased to 2.08 ng/mL, testosterone levels increased significantly, and the tumor size decreased. CONCLUSIONS: Although more cases and investigations into the mechanisms underlying these effects are needed, these 2 cases support the hypothesis that the combination of metformin and bromocriptine might be a new treatment for resistant prolactinomas.