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Prolactinomas in men are usually macroprolactinomas and other investigators have attributed bigger size of tumors in men to delay in diagnosis. A retrospective study of 71 macroadenomas (42 men) was carried out. Parameters studied were age, signs and symptoms at presentation, time of onset of symptoms, basal prolactin, estradiol, and total testosterone levels, tumor size and Ki 67 expression in tumor tissue. Male patients were older. Visual defects were significantly more prevalent in men. Hardy 4 stage tumors were found only in men. We found no significant correlation between tumor size and the patients age nor between tumor size and the onset of symptoms. Whereas basal E2 levels (21.2+/-12.9 vs. 33.3+/-43.3 pg/ml, p=n.s.) were very similar in male and female patients, testosterone levels were significantly higher in men (0.6+/-0.5 vs. 1.8+/-1.2 ng/ml, p=0.02). The rate of cell proliferation represented by Ki 67 was significantly higher in tumors in men (3.5+/-1.2 vs. 1.5+/-0.5%, p=0.0001). This is the first study focused in macroprolactinomas that shows that they are clinically and biologically more aggressive in men. Hypogonadism in men could appear later in the progression of prolactinomas and this might explain why men were older at the time of diagnosis. Furthermore, testosterone could be a source for E2 in situ aromatization giving male tumors an advantage in cell proliferation., (Copyright (c) 2010 S. Karger AG, Basel.)