What Is PMDD?

PMDD (premenstrual dysphoric disorder) is often referred to simply as “bad PMS”, doing women dealing with this issue a huge disservice as it’s much more disruptive to daily living that typical PMS and it’s underlying causes are more nuanced making it difficult to treat.

While some underlying issues of hormonal fluctuations and neurotransmitter imbalance exist in both conditions, there are some key differences between PMS and PMDD:

Symptoms of PMS Include

• Lower mood and energy
• Cramping
• Breast tenderness
• Water retention and weight gain
• Increased appetite and sugar cravings
• Changes in bowel movements (often constipation leading into looser stools with onset of period)
• Breakouts
• Changes to libido
• Insomnia
• Abdominal bloating

Symptoms of PMDD include any physical symptoms of PMS as well as:

• Significant emotional disruption that can include depression, irritability, sudden and severe sadness, increased conflict in work and personal relationships, increased sensitivity and  tension
• Less interest in things that are usually enjoyable
• Extreme fatigue and/or increased need to sleep (hypersomnia)
• Difficulty concentrating
• Sense of overwhelm or feeling out of control, increased need to sleep/hypersomnia
• Increase appetite or cravings that can lead to significant overeating

 

If you prefer to listen instead of read, I cover PMDD on this episode of the Dr Brooke Show.

 

Conventional Medical Treatments for PMDD

Treatment for PMDD includes the birth control pill and often an antidepressant such as an SSRI (serotonin reuptake inhibitor) as well.

These medications can offer some relief but they can of course bring with them other unwanted side effects or in some cases, they can exacerbate PMDD symptoms.

More aggressive treatments for PMDD include GnRH (gonadotropin releasing hormone) agonists or even hysterectomy to entirely stop cyclical hormone changes. However, after a hysterectomy it’s often recommended women take HRT for bone health, etc. and this can of course trigger PMDD again.

What’s particularly interesting is that PMDD is not simply a case of high or low hormones, but rather an instance of sensitivity to hormonal changes as most women with PMDD will show normal serum levels of estrogen and progesterone on testing. Yet when we look deeper some women do display difficulty with estrogen metabolism (i.e. estrogen dominance) and a relative higher estrogen lower progesterone picture, however a more overarching factor is that women with PMDD are overly sensitive to fluctuations in their female hormones rather than an over excess of either estrogen or progesterone.

These normal fluctuations can trigger significant changes in mood and sense of wellbeing as both estrogen and progesterone have an intricate relationship with our brain chemistry.

 

Understanding the Chemistry of PMDD

Here’s the big picture view of how our female hormones and affect mood:

In short, estrogen supports serotonin and progesterone helps GABA. When you have adequate serotonin and GABA you feel happy and not cranky, anxious or irritable.

 

Estrogen & Serotonin

Estrogen is typically highest the second week of your cycle, with a little bump up again around day 21. Estrogen is involved directly in serotonin production from tryptophan and is important for serotonin receptors to function properly so it is key to proper sleep, a sense of calm, an optimistic mood, balanced appetite and even enhanced creativity.

On the other hand, too much estrogen can negatively impact mood as it can (along with stress and inflammation) ramp up production of kyenurate from tryptophan instead of it making serotonin. Normally 95% of our tryptophan goes to kyenurate and just 5% goes toward serotonin, so shifting this pathway even a bit can really tank overall serotonin and thus sleep and mood very quickly.

Finally, we know that SNPs or genetic variations in the ESR1 gene makes us more sensitive to estrogen resulting in more significant estrogen related changes in mood. This is an area worth exploring for women with PMDD as this may play a previously overlooked role in this condition.

It’s clear that to keep serotonin levels adequate we truly need enough, but not too much estrogen. And like most hormonal issues, we want to keeping stress and inflammation in check as they profoundly affect all hormonal and neurotransmitter levels.

 

Natural Treatments That Impact Both Estrogen and Serotonin

Vitamin B6 as it impacts serotonin synthesis and estrogen metabolism in multiple ways.Doses up to 200mg per day can be helpful but start with 50mg per day (too  much B6 can be problatic and cause neuropathy, so use guidance for higher dosages).

It is also wise to ensure you are not low on iron as this is also key for serotonin production.

CBD and l-theanine can be helpful and be careful not to overdo supplementation of DIM or indole 3-carbinol as these are widely used for “estrogen imbalances” but without guidance can result in lower estrogen which may not be ideal.

Finally, balancing blood sugar, managing stress and addressing inflammation will also be very helpful.

 

Progesterone & GABA

Progesterone can be made in the adrenal glands if you’re not ovulating but the largest amounts are produced in the ovary after ovulation and it is typically highest day 21 of our cycle (or rather 7-10 days after ovulation).

GABA (gamma aminobutyric acid) is our main calming neurotransmitter and it is made in the brain as well as the beta cells of our pancreas, ovaries, kidney lung and liver and it’s impacted significantly by progesterone.

Progesterone and it’s precursor pregnenolone, will convert to a neurosteroid called allopregnanolone in our brains and this will bind to the GABA receptor when the receptor is in the correct configuration causing relaxation and calm.

Our GABA receptors normally reconfigure their five subunits throughout our cycle in response to normal changes in female hormones and thus neurosteroid levels (very cool, right?) but a rapid withdrawal or dip in progesterone at the end of the cycle can upset the GABA receptor. When there is a quick drop from progesterone or for some other reason you don’t shuffle those GABA receptor subunits properly, allopregnanolone may not bind to cause the relaxation that should come from GABA receptor activation leading to anxiety, insomnia and agitation.

This is a leading theory in PMDD called  “neurosteroid change sensitivity” where women don’t respond well to fluctuating levels of allopregnanolone leading to many of the mood related issues of this condition. This is likely why some women with PMDD feel much worse using progesterone replacement. Herbs that support the GABA pathway such as valerian, chamomile, hops and lemon balm as well a l-theanine, magnesium and CBD can be helpful in this case.

This is a great formula that I use in my practice to support GABA.

However some women with low progesterone and low allopregnanolone can also have PMDD so this neurosteroid change sensitivity is likely not the only mechanism of this condition so it’s wise to also look at inflammation, estrogen and two other brain chemicals: glutamate and histamine.

I cover why some women do not tolerate progesterone in this episode of the Dr Brooke Show.

 

Estrogen, Progesterone & Glutamate

Glutamate, our most stimulating neurotransmitter, needs to exist in a healthy balance with our calming chemical GABA. Glutamate is converted to GABA by the enzyme GAD65 (l-glutamic acid decarboxylase).

GAD65 requires vitamin B6 so again, B6 deficiency can hinder mood in multiple ways. Some women may have antibodies to their GAD65 antibodies leading to lower levels of GABA and more glutamate. More glutamate means agitation, headaches, insomnia and irritability. There is also an association between GAD antibodies and gluten sensitivity so if you have issues with low GABA it’s worth exploring a gluten free diet.

This pathway doesn’t escape the impact of inflammation and stress either as when we’re under stress our CRH (cortisol releasing hormone) increases which will boost glutamate (due to decreased anandamide). Anandamide is a neurotransmitter and endocannabinoid that binds our own cannabinoid receptors. It’s been called the “bliss molecule,” aptly named after ananda, the Sanskrit word for “joy, bliss, or happiness.”  If stress seems to make mood or PMDD issues worth, CBD may be a helpful treatment.

Excess glutamate may be an issue for you if you get agitated from taking the supplement l-glutamine (common in gut healing regimens and many workout recovery products), get agitated or migraines from MSG (mono-sodium glutamate) or have mood related issues when you eat gluten.

 

Female Hormones & Histamine

Histamine is commonly thought of only in relation to allergies and hives but it is not only part of our acute inflammatory reaction it is also a stimulating neurotransmitter (like glutamate) and has an interplay with estrogen and progesterone.

Inflammatory conditions ranging from skin issues (acne, eczema, hives, itching, etc.) and digestive trouble as well as painful or irregular menses, irritability, insomnia, headaches or even frequent urination may be related to excess histamine. Interestingly histamine issues are exacerbated by estrogen and improved by progesterone.

Histamine may be worsening your PMDD issues in particular if:

• Anxiety is key symptoms
• You get headaches or migraines with ovulation or leading up to your period
• If you have itching, hives or dermatographia (slightly scratch your skin and look for a raised red mark)
• Breast or pelvic pain
• Have digestive changes with your period

Histamine balance can be improved with vitamin C (particualrly helpful if blended with other bioflavanoids such as in this product) and again, vitamin B6. It may also be worth exploring a lower histamine diet or at the very least going dairy free. Dairy is a significant histamine trigger and one component of diary, casein-derived neuroactive peptide (BCM7) will negatively impact GABA levels.

You can see that PMDD is not likely to be solved by one medication or supplement intervention but rather several mechanisms are likely involved for women suffering with this issue.

 

Here’s a recap of how to best address this complex condition:

Nutrition

Ensure balanced blood sugar with adequate fibrous veggies and protein at each meal and taking the time to find your unique carb tolerance (which types and amounts of starchy carbs and fruit work best for you). And don’t forget sleep and stress will profoundly affect blood sugar as well, it’s not just about what you eat.

Manage all sources of inflammation which range from not enough sleep, too much stress, over-exercising, food sensitivities, gut health, etc. This is exactly what I do in my pracitce so please reach out for help!

Consider glutamate and histamine intolerances  (more on Histamine Intolerance in this article) especially if your symptoms seem worse on popular healthy foods such as bone broth, fermented foods, collagen powders and even spinach, avocado or banana.

Consider both a gluten and dairy free diet especially if you have irritability, anxiety or insomnia as part of your PMDD picture.

 

Supplements

Vitamin B6 is a clear leader as it affects so many neurotransmitter pathways as well as estrogen metabolism. 50mg-150mg of activated B5 (pyridoxal 5 phosphate) not to exceed 200mg per day.

Magnesium 300-1200mg per day to support GABA pathways, healthy progesterone levels, cortisol production and many, many biochemical reactions. If anxiety and insomnia are significant magnesium glycinate is the best form.

GABA supportive nervine herbs such as valerian, chamomile, hops and lemon balm.

Turmeric (1-3 grams per day ) and omega 3 fatty acids from high quality fish oil (2-4g per day) can be helpful if inflammation is a part of your PMDD picture.

CBD and l-theanine are also both very helpful if irritability and insomnia are significant symptoms or if stress makes your PMDD issues worse.

Consider testing female hormone metabolism with tests such as DUTCH to better understand if supporting these pathway would help your PMDD symptoms vs. trial and error with supplements such as DIM or vitex to balance estrogen and progesterone.

 

Medications

Discuss bioidentical progesterone with your provider and carefully monitor symptoms and levels.

Oral bioidentical progesterone more readily converts to allopregnanolone than topical, however topical progesterone has been shown to be helpful as well. Progesterone is tricky though and espeically in PMDD as many women feel much worse on it.

Synthetic progestins (such as drospirenone, levonorgestrel, or medroxyprogesterone orally or as part of IUDs such as Merina or Skyla) are not recommended as they are not the same as your own progesterone and many carry significant mood issues and depression as side effects.