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Objective: To analyze the hormone production profiles of prolactinoma and to analyze the clonality of prolactinoma., Methods: Clinicopathologic factors were studied in 123 patients with prolactinoma, 40 males and 83 females, aged 31.9 +/- 12.2 (16 approximately 65) who underwent resection of tumor in Japan. The specimens were fixed in either 10% neutral buffered formalin or 70% alcohol and used for light microscopy. DNA was extracted from 26 samples of alcohol-fixed tissue from female patients for human androgen receptor gene (HUMARA) assay. The data underwent Spearman rank correlation analysis and nonparametric Mann-Whitney U test., Results: sixty-one cases (50%) were pure prolactinoma and 62 cases (50%) were plurihormonal prolactinoma. Spearman rank correlation analysis revealed that age was significantly positively correlated with serum prolactin (PRL) level (P = 0.0002), and tumor volume (P < 0.0001); and tumor volume was significantly positively correlated with serum PRL level (P < 0.0001). Multiple regression analysis showed a significant correlation only between tumor volume and serum PRL level (multiple correlation coefficient = 0.622, coefficient of multiple determination = 0.387, t = 7.59, P < 0.0001). Mann-Whitney U test revealed that the invasiveness of tumor was significantly positively correlated with the serum PRL level (P < 0.0001), volume of tumor (P < 0.0001), and the age of patient (P = 0.0003); that the sex of patient was significantly positively correlated with the pre-and post-operative serum PRL levels (both P < 0.0001) and the tumor volume (P < 0.0001); and that male patients had significantly higher PRL levels and larger adenomas(P < 0.0001, P < 0.0001 respectively). The HUMARA assay disclosed that 11 of the 13 plurihormonal prolactinomas (85%) were compatible with monoclonal origin., Conclusion: Prolactinoma secrets not only PRL but also other pituitary hormones. Most multihormone producing prolactinomas are monoclonal in origin.