If COMT is slow and is also suppressed by elevated estrogen, how can one feel comfortable with high estrogen levels in the middle of the cycle? Wouldn't the administration of progesterone then stimulate COMT activity and thereby reduce catecholamines? And wouldn't low COMT levels cause more symptoms of estrogen dominance in the first half of the cycle?
That’s such a great and thoughtful question—thank you for asking it!
The key distinction here is between elevated estrogen levels and excess estrogen load. “Excess” doesn’t necessarily mean estrogen is high; it means it’s not being efficiently metabolized and cleared, often due to sluggish liver detoxification, methylation issues, or slow COMT activity. So even if levels aren’t elevated, your exposure can still feel excessive.
Estrogen and progesterone work like a see-saw: estrogen peaks in the follicular phase, then drops as progesterone rises in the luteal phase. When progesterone doesn’t rise enough—or estrogen isn’t cleared efficiently—that balance is disrupted. Progesterone does support COMT, yes, but I was referring to its natural cyclical rise, not to administering progesterone. If detox pathways are sluggish, progesterone alone won’t correct the buildup; methylation, liver function, and estrogen clearance need support too.
And as I note in the article, this pattern shows up most clearly in women with the low-activity COMT genotype—the Deep Feeler type—while those with balanced or fast COMT types may experience very different chemistry.
I go into much more detail (including step-by-step strategies for each COMT type) in The COMT Midlife Action Guide, if you’d like to explore it further. I find epigenetics really interesting. :-) As always, this information is for educational purposes only and isn’t a substitute for medical advice. If you’re exploring hormone balance or genetics-based support, it’s best to do so in collaboration with your doctor or licensed health practitioner.
If COMT is slow and is also suppressed by elevated estrogen, how can one feel comfortable with high estrogen levels in the middle of the cycle? Wouldn't the administration of progesterone then stimulate COMT activity and thereby reduce catecholamines? And wouldn't low COMT levels cause more symptoms of estrogen dominance in the first half of the cycle?
That’s such a great and thoughtful question—thank you for asking it!
The key distinction here is between elevated estrogen levels and excess estrogen load. “Excess” doesn’t necessarily mean estrogen is high; it means it’s not being efficiently metabolized and cleared, often due to sluggish liver detoxification, methylation issues, or slow COMT activity. So even if levels aren’t elevated, your exposure can still feel excessive.
Estrogen and progesterone work like a see-saw: estrogen peaks in the follicular phase, then drops as progesterone rises in the luteal phase. When progesterone doesn’t rise enough—or estrogen isn’t cleared efficiently—that balance is disrupted. Progesterone does support COMT, yes, but I was referring to its natural cyclical rise, not to administering progesterone. If detox pathways are sluggish, progesterone alone won’t correct the buildup; methylation, liver function, and estrogen clearance need support too.
And as I note in the article, this pattern shows up most clearly in women with the low-activity COMT genotype—the Deep Feeler type—while those with balanced or fast COMT types may experience very different chemistry.
I go into much more detail (including step-by-step strategies for each COMT type) in The COMT Midlife Action Guide, if you’d like to explore it further. I find epigenetics really interesting. :-) As always, this information is for educational purposes only and isn’t a substitute for medical advice. If you’re exploring hormone balance or genetics-based support, it’s best to do so in collaboration with your doctor or licensed health practitioner.