Two Cases of Severe PMS – the importance of lab testing

Updated: Mar 30

Today’s article is a little different, in that I want to show you how lab testing can give us an extremely clear picture of what is going on hormonally, and how to proceed with treatment. I’m going to share with you a two patient cases that I have worked with over the past month and how unique we all are when we dive deeply into lab testing.

My philosophy has always been “test, don’t guess,” because in some cases, what appears to be the same symptom presentation – in these cases very difficult PMS, can have a completely different underlying cause.

Case #1 – “Terrible PMS” lasting 1.5 weeks each month

This is a woman in her mid-20’s who has very difficult menstrual cycles: periods are getting heavier and more painful, and many premenstrual symptoms: moody, tender breasts, fatigue, full-body water-retention, bloating and weight gain, all lasting for approximately 10 days each month. The important note in this case is that several years ago, she lost her period for 2 full years with an eating disorder (very low calorie nutrition and significant weight loss). She is now at a healthy BMI, eating a fairly balanced diet and exercising moderately. Periods and PMS before the eating disorder were not nearly this difficult.

We did two types of lab testing: bloodwork to check luteal phase hormones (estrogen and progesterone), free T3 as a marker of metabolic stress, morning cortisol. The second test was the DUTCH hormone test which maps out hormone pathways and metabolites.

Lab results:

The most notable findings were on the DUTCH test: high-normal DHEA level (an adrenal androgen), and very high estrone levels. (Image below – hormones are starred). DHEA in this range is quite common, and can lead to a few annoying androgenic symptoms in most cases, especially acne, which is exasperated during stress. The very high estrone was the most unusual finding: this hormone is produced from DHEA, and is formed in the adrenal glands and abdominal fat cells (not the ovaries), and is unusually high in a woman in her mid-20’s, and a healthy body weight. This is where the extra estrogen is coming from which is creating all of the premenstrual symptoms.

Bloodwork showed low, but ovulatory levels of progesterone, low-normal morning cortisol and normal free T3 indicating that she is now fueling herself adequately. The combination of high total estrogen load and low progesterone together make a very strong estrogen dominance, again amplifying the premenstrual symptoms.

Interpretation and treatment:

My interpretation is based on the unusually high estrone level. I suspect that this pathway got activated during the eating disorder times, as a smart body mechanism to protect the brain, heart and bones when body fat was so low. This pathway is still activated strongly, and is significantly increasing the estrogen load leading to premenstrual moodiness, water retention, heavy flow and breast tenderness).

We can also look at the full hormone pathway picture, and see that her body is shunting a significant amount of hormone resource (pregnenolone) towards DHEA —> estrone, and less towards progesterone and cortisol. What this means is that the body is prioritizing estrogen production, at the expense of cortisol (which manages stress), and progesterone (which is essential for fertility).

This pathway map also helps us to see strategies to shift the hormones: using natural aromatase inhibitors (flaxseeds, green tea, mushrooms, soy, quercitin) to reduce DHEA —> estrone pathway especially, and also some licorice extract to reduce DHEA and create more Cortisol.

As you can see in this case, the hormone mapping provided enormous clues in how to restore hormone balance and relieve PMS. Yes, it is an estrogen-dominance pattern, but a unique one with a remnant from eating disorder times of a strong pathway making excess estrone, and greatly increasing the total estrogen load.

Case #2: PMDD – Unable to function for 10 days of the month with severe premenstrual depression and irritability

This is a woman who is just 40, and came in to discuss strategies to help her PMDD (premenstrual dysphoric disorder), which is essentially a more extreme version of the mood changes with PMS. She describes it as 10 days where she is not able to function with foggy head, fatigue, severe depression, sense of doom and irritability. She also experiences more typical premenstrual symptoms like bloating, cramps and breast tenderness. Periods come regularly and last about 3 days.

We began with bloodwork – testing on day 3 of the cycle, and also day 21 to map out the hormones and determine if the symptoms were related to a clear hormone imbalance. She had also previously done personal genetic testing through 23&me, and shared with me her genetic data to look at for methylation, detox pathways and neurotransmitter balance.

Lab results:

Bloodwork showed very normal hormone levels on day 3 – no sign of perimenopause yet with FSH, LH and estradiol in optimal ranges. Lab testing on day 21 showed both high-normal estradiol and progesterone. This is not a clear case of estrogen dominance or low progesterone, but does suggest there may be issues with clearing the high hormones.

Review of personal genetics was actually the most relevant in this case with two significant findings:

  1. Two slow COMT pathways

  2. Issues with the TPH2 gene

The COMT gene impacts two systems: how quickly we breakdown and process catecholamines and dopamine, and also estrogen detoxification. When the gene is slow (as seen in the red below), it means that after a period of stress, the adrenaline and norepinephrine continues to circulate for a long time, and the feeling of stress and anxiety can persist. It also indicates some issues with detoxification of estrogen, which we have in high levels here.

Overall with this gene in the red (meaning pathways are slower), I would expect someone who is very sensitive to stress, and tends to be anxious, and also symptoms of estrogen dominance like premenstrual bloating, breast tenderness, moodiness and water retention.

The TPH2 gene reflects on step in the conversion of tryptophan (an essential amino acid from food) to 5-HTP which is a precursor or serotonin. When this pathway is slow, and especially if there are not enough building blocks with tryptophan and cofactors like vitamin B6, we would expect to see signs of low serotonin such as depression, anxiety and insomnia.

Interpretation and treatment:

From lab findings, we can clearly see the pattern which has created the PMDD symptom: high hormone production with issues clearing estrogen; sensitivity to stress with difficulty clearing catecholamines (adrenalin and norepinephrine), and low serotonin production with a slow TPH2 gene. Put together it’s a perfect storm for menstrual mood disorders.

The good news is that all of these are steps we can modify, with correct nutrition, supplementation and lifestyle support. Here is a very brief summary of the steps:

  1. Ensure nutrition has adequate protein, especially foods high in tryptophan: nuts and seeds, poultry, shellfish, oats. Also support estrogen detox with higher-fibre intake, and a full spectrum of colourful vegetables and fruits.

  2. Additional support for serotonin production: essentially bypassing the genetic issue with supplemental 5-HTP, along with cofactors like vitamin B6 and magnesium.

  3. Emphasizing stress-reducing activities on a daily basis – meditation, yoga, regular downtime, breathing exercises, biofeedback.

  4. Additional supplements to help with hormone detoxification pathways through the liver – containing ingredients such as DIM, indole-3-carbinol, calcium d-glucarate and turmeric.

As you can see in this case, we wouldn’t have seen the whole picture without looking at the personal genetics. By understanding the mechanisms at play, we can build a very precise and personalized treatment plan, along with an understanding of why the symptoms have appeared.

What’s Next?

I hope I haven’t lost you with the complexity of the lab testing and biochemistry in these two cases! What I wanted to share is that when we look at the correct lab assessment, we can clearly understand where the imbalances are that are unique to you. If you’re interested in digging deeper into your hormone balance, and understanding with more clarity, there are some amazing lab assessments that can help.

Book an appointment with Dr. Darou online. Contact us: 416.214.9251,


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