19. Clinical Insights into PMDD, Severe PMS & the Role of Methylation

In this episode of The Histamine Well, Joanne dives deep into Premenstrual Dysphoric Disorder (PMDD) and severe PMS — the kind that can leave you feeling anxious, depressed, exhausted, and unlike yourself for half the month.

Joanne shares insights from her clinical practice to explore what’s really going on beneath the surface, including:

• Hormone imbalances like estrogen dominance and low progesterone
• Inflammation, oxidative stress, and their impact on ovulation
• Nutrient deficiencies that affect mood and hormone function
• The surprising role of methylation imbalances — particularly overmethylation — and how this biochemical pathway can disrupt neurotransmitters and mood

She also introduces the concept of testing methylation in real time, and shares a powerful patient story that shows how personalized treatment can dramatically improve mood and cycle symptoms.

Whether you’ve been diagnosed with PMDD or you just know your PMS isn’t normal, this episode offers a fresh perspective and hope for more stable cycles and moods.

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Transcript

Joanne Kennedy: 0:00

Hi, it's Joanne. In today's episode, we're diving deep into premenstrual dysphoric disorder and severe PMS. The kind that leaves you depressed, anxious, exhausted, overwhelmed, and not feeling like yourself For half of the month. I'll walk you through what's really going on beneath the surface. From hormone imbalances to nutrient deficiencies, inflammation, and even methylation imbalances that could be really impacting your mood and your hormones. Whether you've been diagnosed with PMDD or you just know your PMS is anything but normal. This episode will give you a fresh clinical perspective on what's driving your symptoms and what you can do to start feeling like yourself again. Welcome to the Histamine Well Podcast designed for practitioners and patients alike. This is your trusted source for insights on histamine intolerance, methylation, gut health, women's hormones, and much more. I'm Joanne Kennedy. Your host, naturopath, author, and educator. Passionate about breaking down complex science into clear, accessible knowledge. Whether you are a health professional or navigating your personal wellness journey, the Histamine Well Podcast bridges the gap between cutting edge research and practical understanding to empower you with the tools to thrive. Hi everyone and welcome back to the show. Today I want to share some insights from my clinical experience working with Premenstrual Dysphoric Disorder or PMDD. But before we dive in, let's zoom out and talk about what PMDD actually is. According to the medical literature, PMDD is a significant hormonal mood disturbance that occurs alongside physical symptoms, typically from ovulation to menstruation. It's important to note that it's not caused by preexisting mental health conditions rather it's hormonally driven. Now I see so many women who come to me with really difficult or severe PMS. Is it PMDD? Maybe. Maybe not. But here's the truth. Whether it technically fits the diagnostic label of PMDD or is just really severe, PMS, what matters most is why a woman's hormonal shifts are having such a profound impact on her mood, and that's where we need to focus. One of the first things that I do is I start with cycle regularity. If your cycle is all over the place, your hormones are all over the place. So if you're having a short cycle under 21 days or a long cycle over 35, getting up to 40-45 days, or you are just a few days off your usual rhythm. That variability can really affect both a woman physically and mentally. So even going from a 28 day cycle to a 26 or a 32 day cycle can make a big difference for women who are sensitive to hormonal shift. One of the first things I do is I try to get the cycle back into a consistent rhythm. That's ideally close to your personal normal, and for many women, that's around 28 days. Regularity helps balance estrogen and progesterone. It's not the only thing we focus on, but it's really important to at least start getting the cycle back to regular. It's definitely what I start to do at the first appointment alongside what else I'm gonna talk to you about. If your cycle is erratic, start to try and get it regulated. Now, obviously you are welcome to work with me. I see patients online via Zoom or other practitioners that can help you regulate your menstrual cycle. Usually with herbal medicine and supplements. Stress management. You need to get your cortisol down. You might have blood sugar issues. You might be underweight. So all of these sort of environmental things need to be addressed. Once you've got your cycle in place, it doesn't mean that it's all perfect. And a lot of women that come to me with PMDD, they do have a regular cycle and they have terrible mood. So what else is going on? First of all, we need to look at oestrogen dominance. It's very common. It's a common part of severe PMS and PMDD. Signs of estrogen dominance include heavy periods, weight gain around the hips and thighs, breast tenderness, bloating and fluid retention, anxiety, irritability, depression, brain fog, and memory issues, fatigue and histamine related symptoms. In these women helping the body detoxify estrogen is key. One of my favorite supplements to do this is calcium d glucarate. It supports a liver detoxification pathway called glucoronidation. Which is one of the pathways that detoxifies estrogen. It downregulates an enzyme in the gut called the beta glucuronidase enzyme. That enzyme deconjugates estrogen. Breaks it, rendering it more active, therefore more circulating estrogen. Now, there are other contributors to high estrogen. Chronic constipation, so if you're not limiting out your agen effectively, that's obviously gonna cause more estrogen. You can have a histamine overload. So histamine definitely increases estrogen. You can have genetic variants such as the COMT enzyme and methylation issues. COMT helps detoxify estrogen, but it needs methylation to be working effectively for that enzyme to work'cause it relies on methyl groups to function. In addition to reducing estrogen, we also need adequate progesterone to balance it. And progesterone is made after ovulation or kind of at ovulation, and then it's secreted with a tissue called the corpus luteum throughout the luteal phase, the second half of the cycle. Progesterone deficiency can present as spotting before your period. Muscle fatigue and inflammation, poor exercise recovery in the second half of the cycle. That's very telling to me of low progesterone, anxiety and insomnia. To support progesterone production, we need some key nutrients. We need zinc, B six, iron, vitamin D, and iodine. So many women are so low in iron. Especially if they're having short cycles and heavy bleeds. They're gonna have really, really low iron, so we need to make sure we get that up. Another thing we really need to understand, this is very important. Is the way inflammation and oxidative stress impacts the cycle. So essentially follicles that grow in the ovary and then at sort of day 14 you get the dominant follicle. They love an environment of low inflammation, low oxidative stress. And when that happens, you can get a nice, healthy, dominant follicle around day 14 that releases the egg. That follicle then forms a tissue called the corpus luteum. And the corpus luteum is a tissue that secretes progesterone. It also loves an environment of low inflammation, low oxidative stress. So my go-to supplements here to support inflammation, oxidative stress are n-acetylcysteine or glutathione. But here's the critical part and what I really hope you get out of this podcast is that if you've done all of that and your mood is still unstable. This is where methylation comes in. And this is so profoundly important to understand. So methylation is a biochemical process that influences neurotransmitter production amongst other things. Okay? So it helps with the production of your dopamine, serotonin, epinephrine, norepinephrine, adrenaline. It also helps detoxify those neurotransmitters. So it's a very balancing. Now methylation is also important for the detoxification of estrogen and the breakdown of histamine. What we are seeing so often is that many women are over methylating due to estrogen. If you know much anything about methylation, you might likely be looking at your gene variants Genes such as MTHFR, MTR, BHMT. These genes are the provide the code for enzymes that are important for the production of methyl groups. And when we look at these genes, we can think potentially this person is an under methylator. Because the symptoms can often be quite similar, especially when it comes to mood. But what we now know is that estrogen pushes most women into over methylating. Over methylation can lead to an excess of neurotransmitters. So you can have too much dopamine and too much adrenaline. Can make you feel wired Jacked up, anxious, ery, overwhelmed. Women who are over methylators tend to be perfectionistic, very empathetic, OCD like tendencies. And then when their hormones change, it just causes more havoc with this excess amount of neurotransmitters. This is why women with PMDD are such classic. Group of patients that I see that are definitely have big methylation issues and often over methylating. We can now test your methylation. We can test it in real time and this is what I'm doing with my patients so that we can understand if you are over or underm methylating. And this is something I'm now doing routinely in patients in my clinic, and it's making a really huge difference. I. So once we know your methylation picture, we can really start balancing out your methylation, which is really supporting your overall mood and allowing you to have the changes in hormones without the huge crash in mood.. So it makes everything way more stable. Let me just share a quick story about a patient I had recently. So a woman came to me, she was vegetarian. She's only eats eggs. She's had long term blood sugar dysregulation. She had the marina inserted and it left her severely unwell mentally. She was put on an SSRI and sleep aids, and ended up developing serotonin syndrome. Likely because she was already over methylating and producing too many neurotransmitters on her own. And to add to that chronic insomnia, perimenopause, and failed HRT attempts. So you get a really complex and overwhelming case. We tested her methylation and sure enough, she was severely over methylating. So knowing this gives us a clear direction. For sure. This is why I wanna talk about this case. We need to stabilize blood sugar. Okay? We've got her eating animal protein at every meal, which she's really bravely committed to. Okay? So we are doing that, and at the same time, balancing her methylation. Now, due to failed HRT attempts in the marina, her menstrual cycle, it's all over the place. That takes a lot of time to correct, but in the meantime, we can stable out her mood and balance her methylation. Thereby these huge fluctuations that she's getting are not causing debilitating symptoms. When I get really complex cases like this, that the women that have unfortunately had really serious adverse reactions to hormones. The pill, the marina, HRT, and been on medications, SSRIs and sleep, things like Tamaz Pan. It can just be a very, it can end up being very overwhelming and you have to zoom out and now we can zoom out and test methylation in real time and correct the methylation, which really helps stabilize the mood. And then the hormones in time if supported correctly, can start to balance out. I hope this gives you a sense of how I work with PMDD in clinical practice. To me, it's not always about whether someone has PMDD, it's more about understanding the drivers of this moon issue. Is it eastern dominance? Is it low progesterone? Is it histamine overload, nutrient deficiencies, inflammation, blood sugar imbalances, or disrupted methylation, or a combination of all. So if you're struggling with PMDD, we are here to help. We see patients globally online via Zoom. You can make a booking with us via my website, joanne kennedy naturopathy.com. So thank you for joining me. I hope you found this episode beneficial. Be sure to subscribe to the histamine well so you don't miss an episode. Leave a review and you can also share this episode with someone who could benefit. If you have any questions you'd like answered. Or have a topic you'd like me to discuss, please go to my website, joanne kennedy naturopathy.com, where you can provide us with that information. Until next time, take care and be well.