Hormonal Balance and the Female Brain
- Jacki Meinhardt
- Dec 31, 2022
- 3 min read
Estrogen and progesterone are vital hormones for overall female health and well-being. From menarche to menopause, the natural fluctuation of estrogen and progesterone affects not only the reproductive organs but also the brain. When these hormones act in the brain, they are referred to as “neurosteroid” hormones. The neurosteroid hormones have two main effects, classified broadly as organizational and activational. Organizational effects are permanent alterations of nervous system structure, including myelination and strengthening of synapses. Activational effects are non-permanent alterations on brain activity through their interaction with neurotransmitters.
Thus, estrogen and progesterone have an effect on memory, mood, cognition, and behavior.
A woman’s mental health can be dramatically affected by alterations in the natural fluctuation of hormones, including changes caused by hormone replacement. The 2018 article by Del Río et al provides a review of steroid hormone production in the female body and their role in the female nervous system.
Estrogen, Progesterone, and the Female Brain
The direct effect of estrogen and progesterone in the brain plays an important role in the permanent structure of the nervous system. In the brain, these hormones act via classical and non-classical pathways. For both hormones, the classical pathway involves diffusion of the hormone into cells, binding to receptors, and then entering the nucleus where they directly affect DNA. The non-classical pathways involve hormones binding to membrane receptors and activating signaling cascades.
Estrogen and progesterone protect the brain, decrease inflammation by reducing free radicals, regulate glucose (sugar) utilization, and induce brain cell repair and growth. Progesterone also plays a role in the regulation of glial cells (brain immune cells) and myelin production (thin layer that protects the brain and nerves) in the central and peripheral nervous systems. However, the central takeaway is that estrogen and progesterone are not synergistic – when given simultaneously, there is an overall lower response in the brain as compared to being given alone or in a natural sequence. Thus, the natural fluctuation in the menstrual cycle is imperative for a proper neuroprotective balance.
Therefore, variations in hormone levels, either naturally or due to hormonal imbalance, can lead to changes in brain chemistry.
Estrogen and Progesterone on Neurotransmitters
Estrogen and progesterone also affect brain levels of various neurotransmitters, including glutamate, gamma-Aminobutyric acid (GABA), serotonin, and dopamine. Estrogen increases the release of glutamate, the main excitatory neurotransmitter in the brain, and increases N-methyl-d-aspartate (NMDA) receptor synthesis and expression. This enhances neuronal excitability and has been shown to improve learning, memory, and other cognitive functions. Estrogen decreases the release of GABA, the main inhibitory neurotransmitter in the brain, promoting increased glutamate and dopamine transmission.
Serotonin is an important contributor to well-being, playing a role in sleep, sexual behavior, mood, and cognitive functions. Estrogen promotes synthesis, prevents degradation, and inhibits reuptake of serotonin; it also promotes the expression of serotonin receptors. Thus, estrogen plays a large role in the overall mood of women. Furthermore, estrogen increases dopamine synthesis and decreases its degradation and reuptake. It improves working memory, decision making, and pleasure.
In contrast to estrogen, progesterone inhibit glutamate transmission, decreasing glutamate release and glutamate-induced dopamine release.
Not surprisingly, stress to include inflammation or immune upregulation, also upregulates glutamate production. It is vital to keep stress under control throughout a woman's menstrual cycle but especially in the luteal phase.
When estrogen is high and progesterone is low (estrogen dominant state) the body favors glutamate over GABA. A potential contributing factor to inadequate conversion includes gluten sensitivity. The gliadin antibodies produced in gluten sensitivity inhibit the enzyme that converts Glutamate back to GABA.
What are easy ways to bring glutamate back into balance:
Magnesium and Vitamin B6: both are essential for converting glutamate back into GABA
L-theanine (green tea extract) – to stimulate GABA.
Relaxing herbal medicines such as Kava, Passionflower & Zizyphus
Adaptogenic herbal medicines such as Withania (ashwaganda) & Rhodiola
Stress management activities such a meditation, yoga and walking in nature
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