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Background: Several pharmacotherapeutic approaches have confirmed the influence of neuroendocrine parameters on sexual desire, function, and fantasies in men; however, the relevance of acute neuroendocrine changes in mediating heightened sexual drive remains unknown. We recently demonstrated that plasma prolactin substantially increases following orgasm in healthy men, suggesting a feedback mechanism for peripheral prolactin in the control of acute sexual arousal. Because prolactin appears to play a regulatory role in acute sexual drive, we initiated this study to see whether sexual offenders with a high sexual drive have a different neuroendocrine response to sexual arousal. This study compares the prolactin response to orgasm of sexual offenders with high sexual drive and that of healthy subjects with average sexual drive., Methods: From a subject pool of 150 inpatients held because of sexual crimes, we recruited 10 volunteers, based on their high sexual drive according to an intensive, semistructured clinical interview. We defined sexual drive by a short refractory period and strong sexualization, or a high frequency of sexual stimulation. We analyzed the acute psychoneuroendocrine response to sexual arousal and orgasm continuously before, during, and after masturbation-induced orgasm in patients and control subjects., Results: Sexual offenders demonstrated higher sexual desire (P < 0.001) and function (P < 0.001) and a more positively perceived refractory period (P < 0.05). Both groups displayed a prolonged, significant increase in prolactin plasma levels after orgasm (P < 0.001). Sexual offenders did not differ from control subjects in neuroendocrine response to sexual arousal and orgasm., Conclusions: These data demonstrate that sexual offenders with a high sexual drive do not differ from control subjects in the postorgasmic neuroendocrine response, particularly in prolactin release. This study confirms that factors other than peripheral hormones influence deviant sexual behaviour.