Premenstrual Syndrome: An Evolutionary Perspective on Its Causes and Treatment

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.

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

“…Indeed, it is possible that this is but one in a suite of secondorder adaptations serving this purpose. Progesterone may exercise a similar antagonistic effect on the availability of iron (see Fessler 2002), and there is evidence that estrogen has an antagonistic effect on the availability of tryptophan (Doyle et al 2007). Like cholesterol, iron and tryptophan play critical roles in infection, suggesting the presence of evolved systems that compensate for the liabilities entailed by reproductive immunomodulation (Fessler 2002;Doyle et al 2007).…”

“…As a consequence, changes must occur in the maternal immune system in order to prevent maternal lymphocytes from attacking the conceptus (Szekeres-Bartho et al 1983). Pregnancy is facilitated by a shift in the Th1/Th2 balance in maternal immune functioning, a move away from those inflammatory responses that pose the greatest danger to the invasive blastocyst and the subsequently semiparasitic embryo (reviewed in Fessler 2002;Doyle et al 2007;Fleischman and Fessler 2011). Importantly, progesterone plays a central role in the immunomodulation necessary to tolerate the halfforeign conceptus (Siiteri et al 1977).…”

“…The downregulation of maternal inflammation is achieved through decreased levels of proinflammatory cytokines and natural killer cells. These changes are the downstream consequence of progesterone-induced blocking factor (PIBF), which shifts the maternal immunological balance toward anti-inflammatory signals (reviewed in Fessler 2001; see also Szekeres- Bartho et al 1995;Doyle et al 2007). Hence, progesterone is essential to pregnancy in part because it commands an immunomodulatory cascade that allows for tolerance of the half-foreign parasitic conceptus.…”

“…Maternal immune tolerance of the conceptus comes at a price as, by lowering host defenses, it increases the chances of infection (reviewed in Fessler 2001Fessler , 2002Doyle et al 2007). PIBF alters the cytokine secretion profile by increasing the production of Th2 cytokines and decreasing the production of Th1 cytokines (Faust et al 1999).…”

Differences in Dietary Intake as a Function of Sexual Activity and Hormonal Contraception

“…The major exogenous progestin that has not been found to have immunosuppressive effects, Desogestrel (Auerbach et al, 2002), was not used by any participants in our hormonal contraception using sample. For an extensive review of the effects of HCPs on immune functioning, see Doyle, Swain Ewald, and Ewald (2007).…”