What’s Driving PMDD? The Latest Science on a Misunderstood Disorder.

 

Premenstrual Dysphoric Disorder (PMDD) is a severe and often debilitating condition affecting around 5-8% of women of reproductive age (1). While the exact cause of PMDD remains elusive, emerging scientific research has shed light on potential drivers, offering hope for more targeted treatment approaches.

Hormonal balance or Sensitivity?

One of the most consistent findings in PMDD research is the heightened sensitivity to hormonal fluctuations, particularly estrogen and progesterone. Unlike typical premenstrual symptoms, PMDD isn’t caused by abnormal hormone levels but rather by an exaggerated response to normal cyclic changes. Studies suggest that women with PMDD exhibit altered gene expression in the brain’s estrogen and progesterone receptors, which may explain their heightened sensitivity (2).

The Role of GABA

Gamma-aminobutyric acid (GABA) is a neurotransmitter responsible for calming the nervous system. Progesterone metabolites, like allopregnanolone, positively modulate GABA receptors, promoting relaxation and mood stability. However, women with PMDD may experience dysregulation in this system. Research published 2020 demonstrated that women with PMDD have altered GABA receptor sensitivity[3]. For women with PMDD, fluctuating allopregnanolone levels could result in a paradoxical effect, contributing to anxiety, irritability, and depression during the luteal phase of the menstrual cycle.

The Inflammatory Hypothesis

Emerging evidence links chronic low-grade inflammation to PMDD. Inflammatory markers, such as C-reactive protein (CRP), have been found to be elevated in women with PMDD (4). Inflammation can disrupt neurotransmitter function, particularly serotonin, which is vital for mood regulation. This may partially explain the effectiveness of herbs that modulate and stabilize the serotonin pathways.

Genetic and Epigenetic Factors

Genetic predisposition also plays a role in PMDD. Twin studies suggest a heritable component, with an estimated heritability of around 50%. Additionally, epigenetic changes—modifications in gene expression influenced by environmental factors—may contribute to PMDD. Stress, diet, and lifestyle could all influence these epigenetic mechanisms, potentially exacerbating symptoms (5).

Gut-Brain Axis Dysregulation

In my practice diet guidance and gut support are a foundational aspect of a PMDD treatment plan. The gut-brain axis—a bidirectional communication pathway between the gut microbiota and the brain—is increasingly implicated in mood disorders, including PMDD. Gut dysbiosis (an imbalance in gut bacteria) can influence estrogen metabolism and inflammatory pathways, potentially exacerbating PMDD symptoms (6).

Neurotransmitters and Serotonin Research in PMDD

Serotonin, a key neurotransmitter involved in mood regulation, plays a critical role in PMDD. Fluctuations in serotonin levels, particularly during the luteal phase of the menstrual cycle, contribute to symptoms like irritability and depression. Research indicates that altered serotonin transporter activity in women with PMDD impairs serotonin availability, which may explain the effectiveness of herbs that act as selective serotonin reuptake inhibitors (SSRIs) in treating the disorder[7]. Additionally, estrogen enhances serotonin synthesis, and its drop during the luteal phase may further disrupt serotonin pathways, exacerbating mood disturbances. Recent studies also highlight interactions between serotonin, GABA, and dopamine, suggesting that imbalances in these neurotransmitters may increase PMDD symptom severity[8].

Moving Forward: A Holistic Approach

Understanding the multifactorial nature of PMDD reinforces the need for individualized care. Conventional treatments like SSRIs and hormonal therapies do not work for many and people are often left feeling disillusioned. Holistic support is foundational, and integrative approaches addressing inflammation, gut health, and nervous system regulation can complement these strategies.

By embracing both scientific advancements and holistic strategies, we can pave the way for better understanding and management of PMDD. Please get in touch and book in to get your own PMDD Holistic Plan.

 

References

  1. Halbreich U, Borenstein J, Pearlstein T, Kahn LS. The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology. 2003 Aug;28 Suppl 3:1-23. doi: 10.1016/s0306-4530(03)00098-2. PMID: 12892987.

  2. Molecular Psychiatry. 2017. "Gene Expression Changes in Women with PMDD Involving Sex Hormone Receptors." Molecular Psychiatry. https://doi.org/10.1038/mp.2017.21.

  3. Psychoneuroendocrinology. 2020. "Altered GABA Receptor Sensitivity in Women with PMDD." Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2020.104764.

  4. The Journal of Women’s Health. 2016. "Correlation between Elevated CRP Levels and Severity of PMDD Symptoms." The Journal of Women’s Health. https://doi.org/10.1089/jwh.2015.5659.

  5. Frontiers in Psychiatry. 2021. "Epigenetic Contributions to PMDD: Genetic and Environmental Interactions." Frontiers in Psychiatry. https://doi.org/10.3389/fpsyt.2021.674710.

  6. Nutrients. 2019. "Gut Health and PMDD: The Role of Gut Dysbiosis and Dietary Interventions." Nutrients. https://doi.org/10.3390/nu11010065.

  7. The Journal of Clinical Endocrinology & Metabolism. 2018. "Altered Serotonin Transporter Activity in Women with PMDD." The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/jc.2018-01722.

  8. Psychiatric Research. 2021. "Serotonin and GABA: Interactions and Their Role in PMDD Pathophysiology." Psychiatric Research. https://doi.org/10.1016/j.psychres.2021.113421.

 
 
Supplement, Inflammation, Female Health, Hormonal balance, Mental Health, Womens Health, PMDDKatherine MatthewsInflammation, PMDD, Hormones, Hormonal imbalance, moodComment