The exact cause of PMS and PMDD is unclear, but it is generally agreed that PMS and PMDD develop through a combination of cyclical changes in hormone levels and dysregulation of brain neurochemical activity. Interestingly, the relationship between hormones and neurochemicals appears to be bidirectional. Hormones activate brain neurochemical pathways, directly or indirectly, and are involved in the regulation of many essential brain functions; in turn, these neurochemicals appear to impact hormones (Rasgon 2001; Andreen 2009; Kuhl 2002; Finocchi 2011). Hormones also interact with the hypothalamic-pituitary-adrenal axis, which then impacts the stress hormone cortisol, another interaction that may contribute to premenstrual symptoms (Segebladh 2013; Girdler 2001).
Estrogen and Progesterone
Young women who have not started menstruation do not have a menstrual cycle, and thus do not experience PMS. Women who have undergone menopause also do not have a menstrual cycle or a luteal phase and thus do not experience PMS. This provides evidence that the hormones progesterone and estrogen contribute to PMS and PMDD. Furthermore, PMS and PMDD occur during the luteal phase of the menstrual cycle, when progesterone and estrogen levels are high (Rapkin 2014; Brzyski 2013). However, PMS symptoms do not appear to solely relate to hormone levels, as researchers have been unable to detect differences in hormone levels or patterns in women with PMS compared with control women (Rubinow 1988; Backstrom 1983; Rapkin 2012).
Another possibility that has received some attention from researchers is that hormone metabolites, or derivatives, may underlie some aspects of PMS and PMDD. For example, several studies have suggested that allopregnanolone, a progesterone metabolite, may be involved in PMS and PMDD (Reddy 2010; Andreen 2006; Backstrom 2011; Nillni 2011; Rapkin 1997; Monteleone 2000; Lombardi 2004; Bernardi 2004; Engin 2007; Klatzkin 2006).
Additionally, the relationship or “balance” between sex hormones in a woman’s body may play a discrete but influential role in PMS and PMDD. For example, the fluctuating balance between sex hormones during a woman’s menstrual cycle influences neurotransmitter systems in the brain, which in turn modulate mood and cognition. This is intriguing because altered activity or signaling of certain neurotransmitter systems is thought to contribute to some PMS symptoms (Steiner 2003; Studd 2011; Hudson 2013). Thus, helping establish balance between sex hormones may relieve PMS symptoms for some women (Studd 2011; Hudson 2013).
The hypothalamic-pituitary-adrenal (HPA) axis comprises two brain regions—the hypothalamus and the pituitary gland—and the adrenal glands, which are found on top of each kidney. These three structures work in concert to regulate neurochemical and hormonal signals passed between the brain and adrenal glands, helping manage the response to stress through regulation of cortisol. This functional group is called the HPA axis (Smith 2006). Deregulation of the HPA axis in women with PMS or PMDD can affect cortisol and allopregnanolone levels, resulting in changes in mood and altered responses to stress (Klatzkin 2010; Segebladh 2013; Girdler 2007; Mortola 1989). A more detailed discussion about the HPA axis is available in the Stress Management protocol.
Serotonin, a neurotransmitter, is involved in the regulation of mood and response to stress, eating behavior, and circadian rhythm (sleep-wake cycle) (Caspi 2003; Parsey 2006; Hainer 2006; Monti 2011). Serotonin activity is partly controlled by ovarian sex hormone levels. Therefore, fluctuations in hormone levels during the menstrual cycle can alter serotonin levels and lead to changes in mood (Benmansour 2012; Rapkin 2012; Yonkers 2008). Some but not all studies have found evidence of a relationship between serotonin signaling and sex steroids in the context of premenstrual symptoms (Clayton 2006; Yen 2013; Dhingra 2007; Gingnell 2010; Magnay 2010; Magnay 2006; Yonkers 2008).
Other Potential Mechanisms
Prolactin is a hormone released by the pituitary gland to stimulate breast development and lactation (Liou 2012), while beta-endorphins are neurochemicals that control pain, reward, and addictive behaviors (Sprouse-Blum 2010; Roth-Deri 2008). Both may play a role in premenstrual symptoms. Women who have PMS may have high prolactin levels or low beta-endorphin levels, and this may contribute to some of the psychological and physical symptoms of PMS (van Die 2013; Cunningham 2009). There is also limited evidence to suggest that thyroid dysfunction may be more common in women who experience PMS (Girdler 1995; Schmidt 1993). Women who suffer from PMS should consider having blood testing to determine whether they have a thyroid hormone imbalance. More information about thyroid hormone testing and correcting thyroid hormone levels is available in the Thyroid Regulation protocol.