Menstrual variation of autonomic balance may be a factor in exacerbations of certain diseases during the menstrual cycle

Exacerbation of certain medical conditions during specific phases of the menstrual cycle has long been recognized. Mechanisms of the cyclic variations are poorly understood, but are often attributed to fluctuations in reproductive hormones. We hypothesize that normal variations in autonomic balance during the menstrual cycle, which likely evolved as adaptations for reproduction, may contribute to catamenial variations in diseases independent of hormonal variations. Emerging evidence suggests that autonomic balance shifts towards sympathetic bias during the second half of the menstrual cycle. This shift can be seen as an evolutionary adaptation to address the immunologic and physiologic demands for successful implantation and gestation. Through direct modulation of lymphoid system and activation of the cortisol pathway, sympathetic bias promotes a shift to relative T helper (Th)-2-biased immunity which may favor maternal tolerance of the embryo by attenuating Th-1-mediated interference of implantation. Immune variance during the menstrual cycle has been implicated in menstrual fluctuations of many diseases, but until now the immune variance has been attributed to female hormonal changes. We propose that shifts in autonomic balance independently contribute to fluctuations in diseases by modulating the immune system. Still further, we propose that many other diseases fluctuate due to the direct nervous system actions of shifts in autonomic balance. Our hypothesis portends new therapeutic paradigms based on cyclical modulation of autonomic balance to address catamenial variations of medical conditions.