Effect of Tamoxifen on the Management of Dopamine Agonist-Resistant Prolactinomas: A Systematic Review

The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy. The presence of estrogen receptors on pituitary tumors, and the variable behavior of pituitary tumors in the presence of estrogen, prompted investigation of the role of anti-estrogen in the treatment of DA-resistant prolactinomas. The goal of this paper is to perform a systematic review of the role of tamoxifen in the treatment of DA-resistant prolactinomas. A systematic review was conducted. Inclusion criteria were case reports, case series, and experimental studies using tamoxifen in DA-resistant prolactinomas. Exclusion criteria included review articles, DA-sensitive prolactinomas, and those that were not previously treated with DA. Data were analyzed using descriptive statistics. For continuous data, the mean was used. For dichotomous data, frequencies and percentages were used. Data on 22 patients were extracted from the seven included studies. Twenty patients (90.9%) responded positively to the use of tamoxifen with a mean reduction in prolactin levels of 57.4%. Ten patients (45.5%) showed normalization of prolactin post-tamoxifen administration. Regression of tumor size and stability of tumor growth were reported in four out of 22 cases (18.2%). Combination therapy with DA and tamoxifen increased DA sensitivity and had a clinically significant inhibitory effect on prolactin secretion. Furthermore, tamoxifen may be considered an effective adjuvant for tumor size control. Therefore, further studies are needed to draw more clinically and statistically robust conclusions.