Serotonergic dysfunction in women with pure premenstrual dysphoric disorder: is the fenfluramine challenge test still relevant?

The fenfluramine (FEN) neuroendocrine challenge paradigm, which involves measuring the response of prolactin (PRL) release to an oral challenge dose of FEN, provides a means of assessing serotonin (5-HT) function. The purpose of this study was to ascertain the role of 5-HT in premenstrual dysphoric disorder (PMDD) by measuring: (1) PRL and cortisol (CORT) responses to FEN; and (2) platelet 3H-imipramine binding levels, in females with pure PMDD (without a past or present comorbid mood disorder) in comparison to healthy controls. FEN challenge tests were administered to nine female patients with pure PMDD and nine healthy female controls during the follicular and late luteal phases of a menstrual cycle. There were no differences in the PRL response to FEN for women with PMDD compared to healthy controls. However, the trend toward a delayed response to FEN and a significant negative correlation between delta(max) PRL and basal CORT in patients but not in controls during both phases of the menstrual cycle suggest an underlying 5-HT dysfunction in patients as compared to controls. This is further supported by the finding of significantly lower Bmax 3H-imipramine binding levels in the patients during the late luteal phase.