Aromatase inhibitors as a therapeutic strategy for male prolactinoma resistant to dopamine agonists: a retrospective cohort study and literature review.

PURPOSE: To assess the effect of letrozole, an aromatase inhibitor (AI), in patients with resistant prolactinoma that presented an increase in serum prolactin (PRL) levels during testosterone replacement therapy (TRT). METHODS: A retrospective cohort study in a single tertiary care center. From March 2012 to July 2023, 53 male patients over 18 years with prolactinoma were followed in our Neuroendocrine Unit. Of those, 90.6% presented macroadenomas, 41% of them were resistant to cabergoline and 25% presented persistent hypogonadism to whom TRT was indicated. Among them, five presented a significant increase in PRL levels and AI was initiated. All five patients had resistant prolactinomas. One of them was excluded due to tumor aggressiveness and concomitant use of temozolomide during AI therapy. RESULTS: Four patients were included in the analysis, with a mean age of 28.5 (± 7.5) years, median prolactin of 1060 (600 to 6700) ng/mL and median of the largest tumor diameter of 3.6 (1.5 to 5) cm at the time of prolactinoma diagnosis. On TRT, all presented an increase in serum PRL levels (231 to 396%), with a subsequent decrease (61 to 93%) after adding AI. During AI treatment for a median time of 60.5 (21 to 120) months, tumor shrinkage was observed in two cases (-8 and -3 mm in the maximum diameter) and tumor stability in the other two. No major side effects occurred and AI was well tolerated. CONCLUSION: AI might be an option for men with resistant prolactinoma who have an increase in PRL levels on TRT. Nevertheless, prospective randomized clinical trials are needed to ensure efficacy and security for this approach.