The PMDD-EDS connection

If you’ve been diagnosed with EDS and notice your premenstrual symptoms are worse than others’, you’re not alone.

In case you haven’t heard of it before, Ehlers-Danlos Syndrome (EDS) refers to 13 rare genetic conditions that affect connective tissue - things like skin, joints and blood vessels. If you have EDS, you probably know all too well about joints that bend too far, skin that bruises like a peach and chronic pain that never goes away.

Now, on the surface, EDS and PMDD seem like they belong in completely different boxes. But here’s the thing - lots of women with EDS say their symptoms flare before their period, or that their pre-menstrual dysphoric disorder (PMDD) feels off the charts compared to others’. And that’s not a coincidence.

What do PMDD and EDS have in common?

It turns out, more than you might think (Lovegrove, 2025):

· Chronic pain

· Mood disorders

· Fatigue

So when your PMDD symptoms show up in the luteal phase (those two tough weeks before your period), they might be stacking right on top of your baseline EDS symptom, making everything feel worse.

This overlap in your symptom suggests a deeper link between EDS and PMDD, that involves your nervous system, hormones, or even how your body responds to stress. The science behind this is still catching up, but here’s what we know so far.

Possible causes

It’s likely there’s no single explanation for why EDS and PMDD seem to go hand in hand. It’s probably a mix of several overlapping features:

1. Hormonal sensitivity

Let’s start with something you might be familiar with if you’ve explored blogs in this series, your ovarian hormones - progesterone and estrogen. With PMDD, your body overreacts to normal fluctuations of these two hormones, triggering your debilitating mood swings, fiery irritability and excruciating pain.

Estrogen and progesterone can also affect your EDS - especially if you have Hypermobile Ehlers-Danlos syndrome. We know that high progesterone in the late luteal phase makes joints more relaxed, so if you’re already hyper-flexible joints can mean increased pain and instability. A surge in progesterone therefore means worsening both your PMDD and EDS symptoms.

2. Chronic pain and fatigue

Pain is nothing new in EDS - you’re dealing with it daily, thanks to connective tissue being involved in every movement. Add PMDD to the mix and you’ve got cramps, headaches and muscle aches layered on top.

It’s no wonder your energy and resilience might be feeling particularly low before your period.

3. Mental health challenges

PMDD is well known for triggering intense mood swings and anxiety. But these symptoms aren’t just limited to PMDD - they might also be a result of your EDS.

Here’s a shared thread running through both conditions: autonomic dysfunction. We talked about this in our post on autism and PMDD, but to recap: autonomic dysfunction means the part of your nervous system that controls things like heart rate, digestion, and stress response starts acting up. And one common result? Anxiety.

So if you’re dealing with both EDS and PMDD, there’s a good chance it’s partly because your nervous system has gone haywire, making you feel overwhelmed, panicky, or emotionally flooded even when there’s no obvious cause.

4. Added comorbidities

Autonomic dysfunction doesn’t just stop at increasing your anxiety. In fact, it’s potentially one of the reasons why Autism and ADHD are more common in women with EDS (Illipse, 2024), as both neurotypes have altered autonomic system activity.

This may seem unrelated but if you’ve read our (PMS vs. PMDD, Severe PMS & PMDD, PMDD symptoms), you’ll know that neurodivergent women are more likely to suffer from worsened PMDD. Therefore, if you have EDS with an added diagnosis of autism or ADHD, the chances you have more intense experience of PMDD are very high.

5. Histamine

Now this feature of EDS and PMDD is really interesting: histamine sensitivity.

Histamine sensitivity is a potential link between why your EDS symptoms worsen if you have PMDD.

Yes, we’re talking about the same histamine that makes you reach for antihistamines during summer. But histamine does far more than just trigger sneezes. It’s also involved in regulating mood, inflammation, and pain.

Histamine is released by a type of cell called a mast cell. If you have EDS, you are more likely to have mast cells that act a little funky, which can lead to developing Mast Cell Activation Syndrome (MCAS), or unpleasant symptoms triggered by histamine fluctuations.

So where does PMDD come in? Mast cells are sensitive to hormones.

In the first half of your cycle - from your period to ovulation (the follicular phase) - mast cells produce more histamine. Your EDS symptoms like fatigue, pain, or emotional reactivity are probably worse during this phase.

Normally, progesterone levels rise in the luteal phase and help calm down your histamine, improving your EDS symptoms. But in PMDD, your brain and body often don’t respond to progesterone the way they should. This means histamine stays high, and your symptoms stay intensified (Illipse, 2024).

Easing your PMDD experience

There’s clearly a lot going on when it comes to the link between EDS and PMDD. It can feel like a tangled mess of hormones, chronic pain, nervous system chaos, and biological processes acting up.

Living with EDS is already exhausting. Add PMDD on top, and the days before your period can feel completely unmanageable. Everything hits harder - your pain, emotional swings and energy levels.

Women with both conditions deserve more research, more recognition and more personalized support. But there are steps you can take to help.

Using Samphire (our app to track your symptoms around your cycle) is a great place to start. It helps you to notice when your symptoms flare meaning you can spot patterns, triggers or even small things that help.

If you’re looking for ways to ease your emotional lows and menstrual pain, gentle brain stimulation from NettleTM might be the relief you’re searching for.

Whilst the research into your condition is evolving, you can take control now with what’s around you - using brain-centred tools to improve your experience with EDS and PMDD.