Sexual hormones influence complex brain function and pain perception. Many psychophysical studies attempted to establish pain perception changes across menstrual cycle in animal models and healthy women or those with chronic pain. General results are quite uncertain in regard to consistent menstrual-related fluctuations of pain perception. The few studies applying neurophysiological procedures to test pain-related changes during menstrual cycle suggested a fluctuation of central modulation of pain across phases, with a prevalence of excitatory versus inhibitory control in the premenstrual period, which may explain the cyclic worsening of many syndromes, such as migraine. Whatever is the relevance of menstrual cycle on individual painful symptoms, it should be accepted as one of the numerous factors influencing mechanisms of neuromodulation.