I had mentioned in a previous post that one way to become a neuroendocrine patient is to possess an anomalous brain in the setting of normal hormones (the other ways were - normal brain, anomalous hormones and anomalous brain, anomalous hormones). Here is a research study that demonstrates this idea in the context of premenstrual syndrome (PMS) from N Engl J Med. 1998 Jan 22;338(4):209-16.
PJ Schmidt et al. from the National Institute of Mental Health set out to induce a reversible chemical menopause in 40 women split into 2 groups - 20 with PMS and 20 without PMS(normal). They gave 10 PMS women and 10 normal women a drug called leuprolide, which fakes the brain/pituitary gland into thinking there is more than enough estrogen and progesterone around and thus causes the pituitary to go quiet and stop stimulating the ovaries to make estrogen and progesterone. The resulting absence of estrogen and progesterone mimics menopause. They gave the other 10 PMS women and 10 normal women a placebo. The 10 PMS women put into "menopause" with leuprolide saw a disappearence of their PMS symptoms. The 10 PMS women on placebo did not.
They then took the 10 PMS women whose PMS-symptoms went away on leuprolide and the 10 normal women on leuprolide and added back estrogen alone for 4 weeks and then progesterone alone for 4 weeks, each time concealing from the women which hormone they were on or whether they were on placebo pills. The women all rated their own symptoms and also had independent raters rate their symptoms.
Giving the PMS women on leuprolide estrogen or progesterone brought back their PMS symptoms where as giving back these hormones had no such effect on the moods of normal women on leuprolide.
The conclusion of the researchers was that women with PMS have an abnormal emotional response to normal hormone changes. This abnormal emotional response is the "anomalous brain substrate" I have previously referred to. Markers of anomalous brain substrate have been identified and consist of things such as a history of mild head trauma or mild abnormal electroencephalogram (EEG) findings, or asymmetrical reflexes on a neurological examination, a family history of major mood disorders, even left-handedness. These sorts of markers are seen with significantly greater frequency in women with agitated PMS compared to women without PMS. It is as if these conditions, or something underlying them, render the woman's brain sensitive to the emotional modulating effects of their own reproductive hormones. Even in PMS women without such overt markers, scientists are actively looking for, and have begun to find, subtle genetic and acquired influences on brain chemistry and brain circuit excitability to explain this sensitivity.
My only surprise with the results of this study was the seemingly similar negative effects of estrogen and progesterone on the moods of these PMS women. In my own neuroendocrine practice I have almost universally seen estrogen and progesterone have opposite effects in women, both on the emotions of women with agitated PMS (estrogen bringing agitation and progesterone bringing calmness) and on brain cell excitability in women with seizures (estrogen pro-seizure and progesterone anti-seizure).