Could Cleaning Your Brain Improve PMDD? What New Research Tells Us About Sleep, Hormones and the Glymphatic System
"Your hormones are normal."
It's a phrase that many people with Premenstrual Dysphoric Disorder (PMDD) hear repeatedly. Yet despite normal hormone levels, symptoms can be profoundly disabling, affecting mood, anxiety, concentration, sleep and emotional regulation for up to half of every month.
At Sirona Health, we've long explained PMDD as a condition of brain sensitivity to normal hormonal changes, rather than a disorder of hormone production. A fascinating new study has added another piece to that puzzle by exploring a part of the brain that many people have never heard of: the glymphatic system.
Although this research won't change treatment overnight, it provides another clue to how sleep, hormones, inflammation and emotional regulation may all be connected.
What is the glymphatic system?
For many years, scientists wondered how the brain removed waste products. Unlike the rest of the body, the brain has no conventional lymphatic drainage system.
In 2012, researchers described what is now known as the glymphatic system. Rather than being a simple bath of cerebrospinal fluid surrounding the brain, fluid flows alongside blood vessels, exchanges with the fluid between brain cells, and helps remove metabolic waste, inflammatory molecules and proteins such as amyloid-beta and tau.
You can think of it as the brain's overnight housekeeping system.
During the day, our brains are incredibly active, producing waste products as a normal consequence of metabolism. During sleep—particularly deep, slow-wave sleep—the glymphatic system becomes much more active, helping to clear these substances before we wake the following morning.
Why does sleep matter so much?
One of the most remarkable discoveries in neuroscience has been that the glymphatic system is most active during deep sleep.
As we enter slow-wave sleep, several things happen simultaneously:
The spaces between brain cells expand.
Levels of noradrenaline, one of the brain's "alertness" chemicals, fall dramatically.
Cerebrospinal fluid moves more freely through the brain.
Waste products are cleared more efficiently.
This may help explain why poor sleep affects far more than simply feeling tired. Sleep disruption influences memory, learning, concentration, emotional regulation and inflammation—many of the very symptoms experienced by people with PMDD.
What did the new PMDD study find?
Researchers recently used an advanced MRI technique called the DTI-ALPS index, which provides an indirect measure of glymphatic function, to compare women with PMDD and women without the condition.
Interestingly, they found that women with PMDD appeared to have higher glymphatic activity, rather than lower.
At first glance this seems surprising. If the glymphatic system helps clear waste, wouldn't more activity be a good thing?
Perhaps—but biology is rarely that straightforward.
Imagine seeing a dishwasher running twice as often. That could mean the kitchen is exceptionally clean. Equally, it could mean there are simply twice as many dirty dishes to wash.
Similarly, increased glymphatic activity could represent the brain responding to greater inflammatory activity, altered hormone signalling or increased metabolic demand, rather than indicating that the system is working "better".
The study also found altered communication involving the hypothalamus, a region of the brain responsible for integrating hormonal signals, sleep, circadian rhythms, temperature regulation and stress responses.
These findings fit remarkably well with what we already know about PMDD, although they certainly don't prove cause and effect.
How might hormones be involved?
One of the biggest misconceptions about PMDD is that it is caused by having too much progesterone or too little oestrogen.
In reality, people with PMDD almost always have normal hormone levels.
The problem appears to lie in how the brain responds to those normal hormonal changes.
Research over the last decade has shown that some women appear particularly sensitive to changes in progesterone and its neurosteroid metabolite allopregnanolone, while emerging evidence suggests that others may be especially sensitive to fluctuations in oestradiol.
These hormones influence far more than reproduction. They also affect:
Sleep quality
Circadian rhythms
Neurotransmitters such as serotonin and GABA
Inflammation
Astrocytes, the support cells that form an essential part of the glymphatic system
Cerebral blood flow
It is therefore entirely plausible that cyclical hormonal changes could indirectly influence glymphatic function through several interconnected pathways.
At present, however, this remains a hypothesis rather than an established mechanism.
Could poor sleep contribute to PMDD?
One of the questions this research raises is whether sleep disruption is simply a symptom of PMDD—or whether it also contributes to it.
Many people describe:
waking repeatedly during the luteal phase
early morning waking
vivid dreams
feeling unrefreshed despite spending enough time in bed
feeling as though their brain never completely "switches off".
If deep, restorative sleep is essential for optimal glymphatic function, then disrupted sleep could theoretically reduce the brain's ability to restore itself overnight.
This raises the possibility of a vicious cycle:
Hormonal sensitivity leads to poorer sleep.
Poorer sleep alters inflammatory signalling and emotional regulation.
Those changes increase sensitivity to hormonal fluctuations.
Symptoms worsen further.
This is an attractive biological model, but importantly it has not yet been proven.
What does this mean for treatment?
At the moment, very little.
This study is exciting because it helps us understand why PMDD may occur, not because it has identified a new treatment.
The evidence still strongly supports established approaches such as:
Selective serotonin reuptake inhibitors (SSRIs)
Combined hormonal contraception for appropriate women
Ovulation suppression in severe cases
Cognitive behavioural approaches as part of holistic care
Optimising sleep and treating co-existing sleep disorders
However, the study does reinforce something that clinicians have recognised for years: protecting sleep is likely to be far more important than simply reducing daytime tiredness.
Sleep is one of the brain's fundamental maintenance processes.
Looking to the future
One of the most exciting aspects of this research is that it moves us further away from viewing PMDD as "just hormones."
Instead, we are beginning to see PMDD as a disorder involving the interaction between:
Hormonal sensitivity
Sleep
Circadian biology
Neurotransmitters
Inflammation
Brain support cells called astrocytes
Neural networks involved in emotional regulation
Rather than searching for a single culprit, neuroscience increasingly suggests that PMDD emerges when several interconnected systems become unusually sensitive to the normal hormonal changes of the menstrual cycle.
The Sirona Health perspective
One study rarely changes clinical practice.
But occasionally, a study changes how we think.
This research is unlikely to alter the way PMDD is treated tomorrow. Nevertheless, it adds another fascinating piece to an increasingly coherent picture: PMDD is not a disorder of abnormal hormones, but of how a susceptible brain responds to normal hormonal change.
As our understanding of the brain continues to evolve, we hope this will eventually lead to more targeted, effective treatments. Until then, the foundations remain the same: evidence-based diagnosis, individualised treatment, and recognising that PMDD is a genuine neurobiological condition deserving of expert care—not dismissal.
Reference
Li Y, et al. Altered glymphatic system activity and hypothalamic connectivity in premenstrual dysphoric disorder: A diffusion tensor imaging study. 2025.
FAQ
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The glymphatic system is a waste-clearance system in the brain. It helps move cerebrospinal fluid through brain tissue, clearing metabolic waste and inflammatory molecules. It appears to be most active during deep sleep.
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A recent study found altered glymphatic system activity in women with PMDD, alongside changes in hypothalamic connectivity. The hypothalamus is involved in sleep, stress, hormones and circadian rhythm, all of which are relevant to PMDD.
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No. This was an early imaging study, so it cannot prove cause and effect. It suggests that the glymphatic system may be involved in PMDD, but we do not yet know whether these changes are causal, compensatory, or simply associated with the condition.
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Deep sleep is when glymphatic clearance appears to be most active. Many women with PMDD experience fragmented sleep, early morning waking or feeling unrefreshed, particularly in the luteal phase. Poor sleep may worsen emotional regulation, inflammation and hormone sensitivity.
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There is no proven “glymphatic supplement” for PMDD. However, regular sleep, exercise, reducing alcohol, treating sleep disorders and supporting overall cardiometabolic health are all biologically plausible ways to support healthy brain function.