The Effects of Estrogen and Progesterone on Blood Glutamate Levels: Evidence from Changes of Blood Glutamate Levels During the Menstrual Cycle in Women

Abstract

The gonadal steroids estrogen and progesterone have been shown to have neuroprotective properties against various neurodegenerative conditions. Excessive concentrations of glutamate have been found to exert neurotoxic properties. We hypothesize that estrogen and progesterone provide neuroprotection by the autoregulation of blood and brain glutamate levels. Venous blood samples (10 ml) were taken from 31 men and 45 women to determine blood glutamate, estrogen, progesterone, glucose, glutamate-pyruvate transaminase (GPT), and glutamate-oxaloacetate transaminase (GOT) levels, collected on Days 1, 7, 12, and 21 of the female participants' menstrual cycle. Blood glutamate concentrations were higher in men than in women at the start of menstruation (P < 0.05). Blood glutamate levels in women decreased significantly on Days 7 (P < 0.01), 12 (P < 0.001), and 21 (P < 0.001) in comparison with blood glutamate levels on Day 1. There was a significant decrease in blood glutamate levels on Days 12 (P < 0.001) and 21 (P < 0.001) in comparison with blood glutamate levels on Day 7. Furthermore, there was an increase in blood glutamate levels on Day 21 compared with Day 12 (P < 0.05). In women, there were elevated levels of estrogen on Days 7 (P < 0.05), 12, and 21 (P < 0.001), and elevated levels of progesterone on Days 12 and 21 (P < 0.001). There were no differences between men and women with respect to blood glucose concentrations. Concentrations of GOT (P < 0.05) and GPT (P < 0.001) were significantly higher in men than in women during the entire cycle. The results of this study demonstrate that blood glutamate levels are inversely correlated to levels of plasma estrogen and progesterone.

The effects of hemodialysis on blood glutamate levels in chronic renal failure: Implementation for neuroprotection

“…Therefore, to reduce glutamate neurotoxicity, it was suggested that we regulate the levels of glutamate in the cerebrospinal fluid (CSF) and ECF by use of familiar mechanisms of glutamate transport from the brain to the blood. In our laboratory, we previously examined various mechanisms to lower glutamate levels including by activation of β 2 -adrenergic receptors and different kinds of hormones [21,[24][25][26].…”

“…Previous studies done by our group and others have shown that pharmacologically reducing blood glutamate levels with glutamate scavengers (such as oxaloacetate and pyruvate) limit glutamate neurotoxicity and provide better neurologic outcomes after various brain insults, particularly traumatic brain injury [14,[19][20][21][44][45][46][47][48][49][50][51][52][53]. Unfortunately, although these treatments have been shown to be effective in animal models of stroke, traumatic brain injury, and subarachnoid hemorrhage, their use in humans is limited by Food and Drug administration restrictions.…”

Risk of Pseudotumor Cerebri Syndrome (PTCS) with hormonal contraceptive use

“…In humans, on days of the menstrual cycle when blood glutamate levels are at their lowest, plasma estrogen levels are at their highest and vice versa, indicating a potential protective role. 18 It has also been speculated that estrogens may promote venous sinus thrombosis, impairing CSF resorption however, in the current study, subjects with cerebral venous thrombosis were excluded from analysis and we are unable to comment on this association. 19,20 Future studies are needed to further examine the role of progestin only contraceptives with PTCS, other than case studies.…”

Effect of estrogens on blood glutamate levels in relation to neurological outcome after TBI in male rats

“…Recently, we have shown in a healthy human population that women have lower blood glutamate concentrations, which fluctuate along the menstrual cycle, inversely correlating with circulating estrogen and progesterone levels [21]. We postulated that this phenomenon is a result of the effect of estrogen and probably progesterone.…”

“…In a recent screening of a human population sample, we revealed that gender is an independent factor influencing blood glutamate, which was found to be decreased in females. Along the menstrual cycle, blood glutamate concentrations fluctuated, inversely correlating with estrogen levels [21,22]. However, the precise mechanism of estrogen-induced neuroprotection remains unclear and warrants further studies aimed at determining the role of glutamate-lowering effect in estrogen-induced neuroprotection.…”