Altered Serotonergic Activity in Women with Dysphoric Premenstrual Syndromes

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Abstract
Objective: Dysphoric Premenstrual Syndromes (PMS) are quite prevalent and in some women they are severe enough to warrant treatment. Their pathophysiology is still unknown, despite increased interest and research. Here we review the possible role of serotonin in the multidimensional interactive pathophysiology of PMS. Method: Over 170 articles are reviewed. An extensive library search has been conducted and articles are included because of their relevance to: 1) the phenomenology of PMS; 2) the putative association of serotonergic (5-HT) activity with syndromes that occur premenstrually; 3) changes in 5-HT activity along the menstrual cycle, especially the late luteal phase; 4) influence of gonadal hormones on serotonergic functions; 5) endocrine strategies for assessment of 5-HT abnormalities; and 6) treatment studies of PMS with serotonergic agonists. Results and Conclusions: The data presented here suggest that post-synaptic serotonergic responsivity might be altered during the late-luteal-premenstrual phase of the menstrual cycle. Some serotonergic functions of women with PMS might be altered during the entire cycle and be associated with a vulnerability trait. It is hypothesized that gonadal hormones might cause changes in levels of activity of 5-HT systems as part of a multidimensional interactive system. Strategies to evaluate 5-HT activities in the context of the menstrual cycle are discussed—leading to the conclusion that the most promising approach is active stimulation with specific post-synaptic serotonin agonists. Treatment outcome studies of some imperfect compounds that are currently applied as a symptomatic treatment of PMS support the notion that 5-HT is involved in the pathophysiology of these syndromes.