Why Hormone Sensitivity — Not Hormone Levels — Causes PMS and PMDD
For years, women have been told their blood tests are “normal” when seeking answers for PMS or PMDD. But new science shows the problem often isn’t the amount of hormones in your body—it’s how your body and brain respond to them. This difference—called hormone sensitivity—explains why debilitating symptoms can occur even with hormone levels that fall within the expected range.
The Role of Progesterone Sensitivity
Progesterone and its metabolite, allopregnanolone, normally have calming effects on the brain. They act on GABA receptors, which help regulate mood and reduce anxiety. But in women with PMDD, research shows these same chemicals may provoke irritability, anxiety, or depression instead.
In fact, a landmark hormone “add-back” study found that women with PMDD experienced symptom relapse when progesterone and estradiol were reintroduced, while women without PMDD did not. Their hormone levels were the same—what differed was their sensitivity to those hormones.
This explains why some women develop severe mood symptoms every luteal phase, while others do not—even with identical hormone patterns.
As women transition into midlife, declining progesterone can make this sensitivity even more noticeable. If you’d like to learn more, I’ve written about why progesterone matters in perimenopause and beyond.
How Brain Chemistry Changes During the Cycle
It isn’t just progesterone. Studies show women with PMDD have altered responses in brain circuits linked to emotion and stress regulation. Instead of stabilising mood, hormonal changes trigger an exaggerated stress response.
One key finding is that the calming effect of allopregnanolone on GABA doesn’t occur as expected in PMDD. Instead, it seems to heighten negative emotions—almost like the brain has rewired how it responds to this hormone.
This sensitivity extends to serotonin, too. Women with PMDD often respond extremely well to SSRIs, sometimes within just a few days—unlike typical depression treatment. That’s because SSRIs increase serotonin availability, helping buffer the brain against the sharp hormonal “switches” of the luteal phase.
Why Normal Hormone Tests Don’t Rule It Out
If you’ve ever been told your hormone tests are “normal,” you’re not imagining your symptoms. Large studies show women with PMDD and PMS often have hormone concentrations indistinguishable from women without symptoms.
What differs is their cellular and genetic response. In one study, researchers examined how cells from women with PMDD responded to estrogen and progesterone in the lab. The PMDD group showed abnormal patterns of gene expression compared to controls. In other words, the body’s reaction to hormones—not their level—was the driver of symptoms.
This is why timing and tracking matter far more than one-off blood tests. Daily symptom diaries and cycle mapping reveal the predictable patterns of hormone sensitivity that lab tests alone miss.
Understanding that hormone sensitivity drives symptoms also explains why diagnosis relies on symptom tracking rather than blood tests. In fact, doctors use structured tools to distinguish PMS from PMDD — I break down the full process in this guide on how PMS and PMDD are diagnosed.
Lifestyle Factors That Make Symptoms Worse
Hormone sensitivity isn’t the whole story. Stress, poor sleep, alcohol, and nutrient deficiencies can all amplify the brain’s reaction to hormonal shifts. For example:
Stress increases cortisol, which worsens mood instability in sensitive cycles.
Poor sleep disrupts serotonin and GABA systems, both crucial in PMS/PMDD.
Alcohol interferes with progesterone metabolism, sometimes worsening irritability or low mood.
Supporting your brain’s resilience through lifestyle—alongside medical treatment—can significantly ease symptoms.
Conclusion: Rethinking PMS and PMDD
The latest science is clear: PMS and PMDD are not caused by “bad” hormone levels. They result from how sensitive your brain and body are to normal hormonal fluctuations, especially progesterone. That’s why treatments targeting sensitivity—whether stabilising hormone fluctuations, using SSRIs, or supporting brain chemistry—often work better than focusing only on hormone levels.
If you’re struggling with PMS or PMDD despite being told your hormone tests are “normal,” sensitivity may be the missing piece.
FAQ
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Hormone sensitivity means your body (especially brain receptors) reacts more strongly to the normal cyclical changes of hormones like progesterone or estrogen, resulting in symptoms even when hormone levels appear “normal.”
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Yes—especially if they’re timed correctly and used alongside symptom tracking. But relying on hormone level tests alone often misses the sensitivity aspect.
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Options include hormone regimen adjustments (stabilising fluctuations), SSRIs, and lifestyle changes such as stress reduction, diet, sleep support, and nutrients that support GABA/serotonin.
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Not everyone—but many people with moderate to severe PMS or PMDD do. Research suggests sensitivity is a key factor for a large subgroup.
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Track your symptoms over multiple cycles, note how they fluctuate in relation to ovulation and your luteal phase, and discuss with a specialist who understands hormone sensitivity (rather than just hormone levels).