Women suffering from severe PMS and PMDD experience depression-like symptoms every month

PET Scan for depression

The brain scans shown above are simplified, and compare the general characteristics of a brain with depressive symptoms to a healthy brain when performing a cognitive task. These scans do not represent the brains of women with PMS or PMDD. We discuss clinical research about changes in women’s brains during their cycles with this image to emphasise the stark difference seen in the brains of women during various phases of their cycles that, in the luteal phase, resemble the brains of those with depression more closely than those of healthy controls. This is also indicative of how little neuroimaging evidence there is in women’s health.

It's all in your brain.

An increasing number of clinical studies are examining the brain in relation to the menstrual cycle, with a particular focus on women with severe PMS symptoms or Premenstrual Dysphoric Disorder (PMDD). By using brain scans, researchers have identified drastic changes in brain activity during the luteal phase (the 5-10 days leading up to your period) compared to the rest of the cycle. These changes are often so drastic that they exhibit patterns of activity similar to those observed in individuals suffering from depression. This important research establishes a vital link between menstrual cycles, mental health, and the lived experiences of millions of women.

Let's explore this science in more detail.

Hormones Impact Everything

We often think about how hormones impact our bodies, but seldom consider their effects on our brain. Fluctuations in estrogen and progesterone levels during the menstrual cycle significantly influence brain functions and mood.

Oestrogen plays a pivotal role in modulating brain function. It's involved in controlling the growth, survival, and activity of neurons. Regarding mood, Oestrogen’s impact on serotonin is paramount. It enhances serotonin's production and receptor sensitivity, leading to us feeling good mentally. That's why in the follicular phase, as oestrogen levels rise, women often feel invincible, experiencing a boost in mood and cognitive abilities

Progesterone, on the other hand, can have a sedative and depressive effect. It peaks during the luteal phase (5-10 days before your period) and influences the production of neurotransmitters like GABA, promoting relaxation but also contributing to mood swings and irritability.

The Dreaded Luteal Phase

During the luteal phase, the surge in progesterone and fluctuating estrogen levels lead to significant changes in brain activity and mood.

A study by Li et al. (2021), revealed that hormonal changes are not just statistical data points but have tangible effects on brain function and, by extension, mood and cognition. The prefrontal cortex, a brain region pivotal for emotional regulation and cognitive processing, becomes less responsive to emotional stimuli during this phase. For women with PMDD, this reduction is pronounced, mirroring patterns observed in depression.

To add to that, the luteal phase also triggers distinct changes in brain wave activity. Baehr et al. (2004) found that alpha waves, which are instrumental in mood regulation, exhibit notable imbalance or asymmetry during this phase. This isn’t a harmless physiological shift. For women, particularly those with PMDD, this alpha wave asymmetry correlates with increased emotional sensitivity, mood swings, and episodes of depression.

In essence, the luteal phase isn’t just a period of hormonal change but a phase where the very foundations of emotional and cognitive well-being are shaken up and recalibrated. Millions of women go through these drastic changes every single month, with little to no validation for their suffering.

The Correlation with Depression - it's Real

Due to some of the phenomena described above, women suffering from severe PMS and PMDD experience depression-like symptoms every month. Let's take a look at the clinical study below, which visually illustrates how real these changes in the brain are:

PMDD phase study

In this study*, the mood of five women with PMDD was tracked over two of their menstrual cycles. The results showed that outside of their PMDD-affected luteal phase (the time leading up to their period), their mood scores were significantly higher and indicated no depression. However, during their PMDD-luteal phase, their mood scores dropped dramatically, well below the threshold that is considered to be depressive (58% PCT). This suggests that these women experienced depressive symptoms specifically during the phase before their period.

*E Baehr, et al., Int J Psychophysiol. (2004)

Put an End to the Monthly Imbalance

Navigating through these sharp and drastic changes in our brains is really challenging, for some it can even be debilitating. What's worse is that women who suffer from severe PMS or PMDD are often not taken seriously and do not receive care or validation for their suffering.

Many women we've spoken to feel like they've tried everything, from traditional treatments like medication and lifestyle changes to hormonal therapies and antidepressants. Yet, the results are often mixed, inconsistent, and sometimes ineffective. While some find temporary relief, the side effects and temporary nature of this relief can be discouraging.

That’s why we’ve spent the past two years developing a medical-grade solution that offers real, uncompromised results: Menstrual Neuromodulation Therapy (MNT). MNT works by directly targeting the parts of the brain that are responsible for mood regulation and generation. It offers an advanced, clinically tested approach to rebalance the brain fluctuations experienced during the menstrual cycle. With MNT, women can feel their best throughout their cycle.

Sign up to our waitlist to stay up to date with more neuroscience and women's health information, and be the first to hear about when our at-home Menstrual Neuromodulation Therapy wearable launches, early next year.

Backed by 8,000+ peer-reviewed research papers

Development and testing of a novel IoT consumer tDCS device for the treatment of primary dysmenorrhea

E Radyte, et al., Brain Stimulation Journal (January, 2023).

Read the paper

Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders

F Fregni, et al., International Journal of Neuropsychopharmacology (April, 2021).

Read the paper

Effects of tDCS for Treatment of Primary Dysmenorrhea: Preliminary Results of a Randomized Sham-Controlled Trial

R Pegado, et al., Pain Medicine (December, 2020).

Read the paper

To have a look at more papers that inspired FireBand, click here.

Meet our Scientific Advisory Board

Professor David Silbersweig
Professor David Silbersweig

Professor of Neuropsychiatry at Harvard and global PMDD neuroanatomy expert. He worked on one of the first pieces of research that showed that PMDD is a neurobiological condition, which laid the foundation for PMDD being recognised by the International Classification of Diseases.

Dr Marie-Christine Nizzi
Dr Marie-Christine Nizzi

Pyschologist and world-leading researcher on innovative clinical interventions. Currently the president of Harvard Alumni for Mental Health and is responsible for developing Samphire's cognitive science-based interventions.

Professor Rodrigo Pegado
Professor Rodrigo Pegado

World-leading chronic pain researcher from Universidade Federal do Rio Grande do Norte. He was the first person in the world to publish a paper on the topic of tDCS to treat pain in dysmenorrhea (menstrual pain).

Professor Maria Theresa Micussi
Professor Maria Theresa Micussi

Researcher from Universidade Federal do Rio Grande do Norte focused on neglected women's health conditions. Responsible for running Samphire's clinical trials.

Dr Sanjula Dhillon Singh
Dr Sanjula Dhillon Singh

Neurosurgeon focused on global public health. Also the founder of the podcast called ‘Science with Sanjula’ where she interviews world-leading scientists about big issues in global healthcare. She is helping Samphire translate our science into public impact.