The Uncertain Etiology of PMS and a Link to Infectious Disease

Science Blogs

Posted on: April 26, 2010 8:00 AM, by Tara C. Smith

Student guest post by Anne Dressler

Ninety percent of menstruating women experience some kind of premenstrual symptoms during the luteal phase of the menstrual cycle, with 20-30% experiencing moderate to severe symptoms. With an even more severe collection of symptoms, is premenstrual dysphoric disorder (PMDD). 3-8% of menstruating women report symptoms severe enough to be considered suffering from PMDD. Yet another designation, premenstrual magnification (PMM), is used to describe women who are symptomatic the entire cycle but have a premenstrual exacerbation of a diagnosed psychiatric, medical, or gynecological condition.

With a large number of wide-ranging symptoms and the difficulty involved in making a diagnosis, it is not surprising that the various theories advanced to explain premenstrual syndrome (PMS) have yet to been proven. One problem is that PMS is a diagnosis of exclusion, meaning there could be a variety of poorly understood conditions responsible for these symptoms. Several theories attribute PMS to fluctuations in sex hormones and neurotransmitters. The observation that symptoms disappear when a women has a menstrual cycle during which she does not ovulate and a corpus luteum is not formed, led to the theory that sex steroids, estrogen and progesterone, produced by the corpus luteum are responsible. In addition, the neurotransmitters serotonin and gamma amino butyric acid (GABA) have been implicated in various pathways. The list of other hormones and their modes of action that are suspected to be involved is long and confusing, making it no wonder that there is still no known etiology.

One distinctly different hypothesis is that PMS is due to a broad set of persistent infectious illnesses that are exacerbated by cyclic changes in immunosuppression due to the fluctuating levels of progesterone and estrogen. In general, there have been studies looking at two major categories of causation- genetic and environmental and have found moderate correlations at the best. Infectious causation has been overlooked for the most part, with almost no empirical support in published literature. I don’t think this means there is no value to the theory, simply that it is a very hard one to test. One very convincing article by Doyle et. al explains how this possibility of infectious causation is integrated with the cyclic changes in hormone levels that have been observed and are generally thought to be involved in PMS.

As the article explains, immune function varies across the menstrual cycle. During the luteal phase, cell-mediated immunity is suppressed and humoral immunity is amplified. This appears to be related to higher levels of progesterone that enhances humoral immunity by promoting the development of type 2 helper T cells. In addition, progesterone is involved in suppressing type 1 helper T cells, which is associated with inhibition of natural killer cells and phagocytosis. This leads to less effective control of various fungi, viruses, and intracellular bacteria. Estrogen also seems to suppress cell-mediated immunity. These hormone driven changes to the immune system provide the possibility that persistent infections may be less well controlled during the luteal phase, leading to the symptoms that make up PMS.

Supporting evidence for this theory is a long list of infections, compiled by Doyle et. al, that are normally controlled by cell-mediated immunity but are exacerbated premenstrually. These include, increased proliferation of Candida albicans, increased proliferation of cytomegalovirus in the cervix, increased number of lesions from human herpes simplex virus-1, and exacerbated peptic ulcers from Helicobacter pylori among others. There are also chronic diseases that have infectious causes or are suspected to have infectious causes that are exacerbated premenstrually. A few examples are, Crohn’s disease, lupus, multiple sclerosis, rheumatoid arthritis, asthma, and chronic fatigue syndrome. The pathogens that are suspected causes for these diseases are also controlled by cellular immunity.

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Author: Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.