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ABSTRACT Premenstrual syndrome is a collection of heterogeneous symptoms that are attributed to hormonal fluctuations and that vary among individuals for unknown reasons. We propose that much of what is labeled "premenstrual syndrome" is part of a broader set of infectious illnesses that are exacerbated by cyclic changes in immunosuppression, which are induced by cyclic changes in estrogen and progesterone. This cyclic defense paradigm accords with the literature on cyclic exacerbations of persistent infectious diseases and chronic diseases of uncertain cause. Similar exacerbations attributable to hormonal contraception implicate hormonal alterations as a cause of these changes. The precise timing of these cyclic exacerbations depends on the mechanisms of pathogenesis and immunological control of particular infectious agents. Insight into these mechanisms can be obtained by a comparison of timing of menstrual exacerbations with the timing of exacerbations associated with pregnancy.
PREMENSTRUAL SYNDROME (PMS) pertains to symptoms that arise or are exacerbated during the luteal phase of the menstrual cycle (the interval between ovulation and the onset of menstruation) and ameliorate after the onset of menses (Deuster, Adera, and South-Paul 1999; Dickerson, Mazyck, and Hunter 2003). PMS is a diagnosis of exclusion, that is, a collection of states united by timing of symptoms and unknown etiologies. PMS therefore may be a catch-all category for exacerbated symptoms of chronic diseases that have not been sufficiently well characterized for their premenstrual exacerbations to be recognized. If so, the PMS category may be largely an artifact of the inadequacy of current knowledge about the true spectrum of chronic diseases, the causes of chronic diseases, and the reasons why chronic diseases are exacerbated cyclically in concert with the menstrual cycle.
HERITABILITY AND ENVIRONMENTAL INFLUENCES
We begin by summarizing what is known about the general causes of PMS. A balanced approach to investigating the causes of chronic illnesses requires that each of the three major categories of causation-infectious, genetic, and noninfectious environmental-be evaluated both logically and empirically (Cochran, Ewald, and Cochran 2000; Ewald and Cochran 2000). Twin studies have yielded only moderate correlations between PMS symptoms and genetic relatedness (Condon 1993;Kendler et al. 1992;Treloar, Heath, and Martin 2002). These correlations provide a sense of the maximal possible genetic influence rather than a demonstration of genetic influence, because environmental correlates of genetic...