Mechanisms involved
This condition is explained through the mechanisms below. Each one is taught as ordinary physiology first.
Primary
Secondary / contributing
Immune cells involvedWho is actually in the tissue
Cycle-timed symptoms with a cycle-timed immune signal underneath.
Selected cell
Macrophage
Clears debris and old blood. When clearance is incomplete it switches to a repair-and-inflame phenotype that feeds fibrosis and new nerve growth.
Luteal-phase inflammatory signalling is measurably higher, which maps onto the timing of mood and pain symptoms.
Schematic drawings, not micrographs. Immune findings here describe mechanism and association; none of them are diagnostic tests.
What it is
Premenstrual dysphoric disorder is a cyclical condition in which mood, sensory tolerance and physical symptoms escalate in the luteal phase and remit within days of menstruation. Hormone levels are typically normal; the difference is in central sensitivity to their change.
How the mechanisms produce this
- Allopregnanolone, a progesterone metabolite, acts on GABA-A receptors. Sensitivity to that shift — not the amount of hormone — appears to drive symptoms.
- The same luteal shift lowers pain thresholds and sensory tolerance, so pain and overwhelm rise together.
- Prospective daily rating over two cycles is what separates this from a mood disorder that simply worsens premenstrually.
What tends to help
- Two cycles of daily symptom rating before treatment decisions.
- Luteal-phase or continuous SSRI, which works on a different timescale here than in depression.
- Ovulation suppression as a second line, with a clear trial endpoint.
- Schedule protection during the known window, treated as an accommodation rather than a preference.
Where the evidence is thin
Why sensitivity to allopregnanolone differs so much between people is not yet explained.