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PMDD: More than just “bad PMS”

Some think of PMDD (premenstrual dysphoric disorder) as “bad PMS.” This is truly a disservice to the women who suffer from PMDD, as it is much more disruptive to daily living that typical PMS and its’ underlying causes are more nuanced. While some underlying issues of hormonal fluctuations and neurotransmitter imbalance exist in both conditions, there are some key differences between PMS and PMDD:

For a discussion of PMS symptoms and some tips on how to naturally alleviate your period woes, check out our article from Lisa Hendrickson-Jacks.

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

Understanding the Chemistry of PMDD

PMDD is not simply a case of high or low hormones. Most women with PMDD will show normal serum levels of estrogen and progesterone when tested, not an excess of hormones. In general, women with PMDD are overly sensitive to normal fluctuations in their female hormones. This can trigger significant changes in mood and sense of well-being as they have an intricate relationship with our brain chemistry.

I will share an overview of how the female hormones affect mood. Estrogen supports serotonin and progesterone helps GABA. When you have adequate serotonin and GABA you feel happy and not cranky, anxious or irritable.

Symptoms of Low Serotonin:

  • Having “the blues” or feeling depressed (and perhaps feeling guilty that you aren’t happier)
  • Losing enjoyment and pleasure from things you used to enjoy
  • Feeling more susceptible to pain
  • More prone to anger than you used to be even when unprovoked
  • Feeling worse in gray, overcast weather

Symptoms of Low GABA:

  • Feeling anxious or panicked or overwhelmed for no reason
  • Feeling knots in your stomach, dread, or doom; inner tension or excitability that’s difficult to turn off
  • Having a restless mind or racing thoughts that  you can’t turn off when you want to relax
  • Worrying or feeling guilty about things that didn’t used to bother you

Estrogen & Serotonin

Estrogen is typically highest during the second week of your cycle, with a little bump up in production around day 21. Because it is involved directly in serotonin production from tryptophan, estrogen is important for serotonin receptors to function properly. 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, along with stress and inflammation, can negatively impact mood as it can ramp up production of kyenurate from tryptophan instead of it making serotonin. This can tank overall serotonin and thus sleep and mood very quickly.

Finally, research shows that genetic variations in the ESR1 gene makes us more sensitive to estrogen-related changes in mood. This is an area worth exploring for women with PMDD.

Progesterone & GABA

The ovary produces the largest amounts of progesterone after ovulation. Progesterone is typically highest day 21 of our cycle, or 7-10 days after ovulation. Progesterone significantly impacts GABA (gamma aminobutyric acid) production. GABA is our main calming neurotransmitter. It is made in the brain as well as beta cells in organs throughout the body.

Progesterone and its’ precursor pregnenolone convert to a neurosteroid called allopregnanolone in our brains. (Fun fact: a synthetic version of allopregnanolone is the active ingredient in the new IV treatment for postpartum depression.) This will bind to the GABA receptor when the receptor is in the correct configuration, resulting in relaxation and calm.

Our GABA receptors normally reconfigure throughout our cycle in response to normal changes in female hormones and neurosteroid levels (very cool, right?). A rapid dip in progesterone at the end of the cycle, however, can upset the GABA receptor. When those GABA receptors don’t reconfigure properly, allopregnanolone may not bind to GABA and cause the relaxation that should come from GABA receptor activation. This is a leading theory in PMDD called  “neurosteroid change sensitivity” and can lead to anxiety, insomnia and agitation. This is likely why some women with PMDD feel much worse using progesterone replacement.

This might not be the only cause of PMDD, so it’s wise to also look at inflammation, estrogen, and two other brain chemicals: glutamate and histamine.

Estrogen, Progesterone & Glutamate

Glutamate, our most stimulating neurotransmitter, needs to exist in a healthy balance with our calming chemical GABA. The enzyme GAD65 (l-glutamic acid decarboxylase) converts to GABA. GAD65 requires vitamin B6, so again, B6 deficiency can hinder mood in multiple ways. Some women may also have antibodies leading to lower levels of GABA and higher glutamate. More glutamate means agitation, headaches, insomnia and irritability. There is also an association between GAD antibodies and gluten sensitivity. 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. 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. Some call it the “bliss molecule,” named after ananda, the Sanskrit word for “joy, bliss, or happiness.” If stress seems to make mood or PMDD issues worse, 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 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 estrogen exacerbates histamine issues and progesterone improves them.

Histamine may be worsening your PMDD issues in particular if:

  • Anxiety is a key symptom
  • 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)
  • You have breast or pelvic pain

Vitamin C and again, vitamin B6, can improve histamine balance. 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 dairy, casein-derived neuroactive peptide (BCM7) will negatively impact GABA levels.

You can see that a single medication or supplement will not likely solve PMDD. I will explain the conventional treatments for PMDD. Then, I will share my suggestions for how to best address this complex condition.

Conventional Medical Treatments for PMDD

Treatment for PMDD often includes the birth control pill and an antidepressant such as an SSRI (serotonin reuptake inhibitor).These medications can bring with them unwanted side effects or exacerbate PMDD symptoms. More aggressive treatments for PMDD include GnRH agonists (gonadotropin releasing hormone) or even hysterectomy to entirely stop cyclical hormone changes. However, after these treatments women often take hormone replacement which can trigger PMDD again.

A functional medicine approach to PMDD


Ensure balanced blood sugar with adequate fibrous veggies and protein at each meal. Take the time to find your unique carb tolerance (which types and amounts of starchy carbs and fruit work best for you). You can check out my step by step process here. And don’t forget–it’s not just about what you eat! Sleep and stress will profoundly affect blood sugar as well.

Manage all sources of inflammation which may include not enough sleep, too much stress, over-exercising, and food sensitivities.

Consider glutamate and histamine intolerances 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 symptoms.

My book Hangry comes out on June 25, 2019. If you pre-order, you can receive bonuses like our 20 page guide to histamine complete with recipes!


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

Iron: adequate iron is also key for serotonin production, so test your levels and supplement as needed.

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.

Herbs: 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 an issue.

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

Consider having a functional medicine provider run a DUTCH test to assess your female hormone metabolism. This will help you 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. DIM and indole 3-carbinol are widely used for “estrogen imbalances,” but without guidance these can result in lower estrogen, which may not be ideal.


Discuss oral bioidentical progesterone with your provider and carefully monitor symptoms and levels. Choose oral bioidentical progesterone if possible. It more readily converts to allopregnanolone than topical; however, topical progesterone has been shown to be helpful as well.

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

A Functional Medicine Approach to PMDDDr. Brooke Kalanick, ND, MS received her doctorate in naturopathic medicine and her masters in both Chinese medicine and acupuncture from the highly acclaimed Bastyr University and has over 20 years of experience working with women as a licensed naturopathic doctor and functional medicine physician. She has helped thousands of women around the world finally feel better through her online programs and one-on-one patient visits with her highly sought after expertise in female hormone imbalance, hypothyroidism, autoimmunity, PCOS, Hashimoto’s, and menopause. Learn more on her website.