Do you find yourself feeling more stressed and moody, with terrible sleep in the days leading up to your period? Or perhaps you are in perimenopause and noticing increasing anxiety, irritability, and a consistently low mood?
If this sounds familiar, it is time to talk about progesterone and its profound impact on the brain.
As a Naturopathic doctor and a Menopause Society Certified Practitioner with a clinical focus on perimenopause, I frequently recommend and manage progesterone therapy for women in perimenopause. This approach, combined with targeted diet and lifestyle recommendations, can be incredibly effective for supporting anxiety, sleep, and mood balance during the menopause transition.
Progesterone Levels Drop, PMS Hits.
How Can a Hormone Influence Your Brain?
Many people think of progesterone solely as a reproductive hormone, but it is also a powerful neurosteroid, meaning it has receptors and significant effects within the brain. There are four key pathways through which progesterone can influence your mood and overall brain health.
1. Progesterone & The GABA Connection: Your Brain’s “Dimmer Switch”
A key metabolite of progesterone, allopregnanolone, acts on the GABA receptors in your brain. When these receptors are activated, it is like turning down a dimmer switch on a bright light. Your brain becomes less overactive and stressed, leaving you feeling calmer and more relaxed. This is also how progesterone is effective to help improve sleep quality. To put it in perspective, benzodiazepines like Xanax and Valium, as well as some sleeping medications, also act on these GABA receptors, but they turn the switch completely off rather than just dimming it.
2. The Serotonin System: A Mood Stabilizer
In combination with estrogen, progesterone interacts with the serotonin system. This is a crucial part of how it helps improve mood balance, particularly for women in perimenopause. The classic example of this is the low mood many women feel just before their period, a time when progesterone levels naturally drop.
3. The HPA Axis: Regulating Your Stress Response
Progesterone can influence your hypothalamic-pituitary-adrenal (HPA) axis, which governs your body’s stress response. It can help reduce your cortisol response and reactivity to stressors. Think of it as narrowing the range of that light switch—preventing the sharp, stressful ups and downs. Research has shown a greater salivary cortisol response to acute stress during the luteal phase (when progesterone is higher) compared to the follicular phase, indicating progesterone’s role in modulating our nervous system’s response to stress.
4. Anti-Inflammatory Action in the Brain
Finally, progesterone has a natural anti-inflammatory effect within the brain, which contributes to its neuroprotective and mood-stabilizing properties.
Perimenopause: A State of Progesterone Fluctuation
Perimenopause is characterized by hormonal fluctuations, often resulting in chronically and sporadically low progesterone levels as menstrual cycles become irregular. Common signs of low progesterone can include shorter cycles, spotting between periods, and skipped periods. This hormonal imbalance is a key reason why many women experience a rise in anxiety, sleep disturbances, and mood swings during this time.
A Therapeutic Option: Micronized Progesterone
For many women navigating the challenges of perimenopause, progesterone-only hormone therapy is one of my top recommendations, integrated within an individualized treatment plan that includes diet, lifestyle, and other supportive therapies.
The form of progesterone I use is micronized progesterone. It is bio-identical to the hormone your body produces and is provided in a micronized form for superior absorption and minimal side effects. This is distinct from the synthetic progestins found in many birth control pills, which are more potent but are also associated with a greater risk of adverse effects.
If you are struggling with mood, sleep, or anxiety, understanding the role of progesterone may be the first step toward finding relief.
References
Jewson, M., Purohit, P., & Lumsden, M. A. (2020). Progesterone and abnormal uterine bleeding/menstrual disorders. Best Practice & Research Clinical Obstetrics & Gynaecology, 69, 62–73. https://doi.org/10.1016/j.bpobgyn.2020.05.004 (ScienceDirect)
“Diagnostic and therapeutic use of oral micronized progesterone in endocrinology.” (2023). British Journal of Obstetrics and Gynaecology. https://pubmed.ncbi.nlm.nih.gov/38652231/ (PubMed)
Oral micronized progesterone for perimenopausal night sweats and hot flushes: a Phase III Canada-wide randomized placebo-controlled 4-month trial.” (2023). Menopause. https://pubmed.ncbi.nlm.nih.gov/37277418/ (PubMed)
Progestagens and progesterone receptor modulation: Effects on the brain, mood, stress, and cognition in females.” (2025). Journal of Psychosomatic Research. https://pubmed.ncbi.nlm.nih.gov/39515587/ (PubMed)
Factors affecting the absorption of MP.” (2016). Journal of Steroid Biochemistry and Molecular Biology. https://www.sciencedirect.com/science/article/pii/S0015028216560312?via%3Dihub
