When we talk about hormones in perimenopause, estrogen often gets all the focus. But for many women, declining progesterone is the real driver behind the earliest symptoms—disrupted sleep, rising anxiety, mood swings, and cognitive fog. Recent research is highlighting just how important progesterone is for protecting brain function, regulating mood, and improving quality of life as hormone shifts begin.
Why progesterone matters for your brain
Progesterone isn’t just a reproductive hormone—it’s also a neurosteroid, meaning it directly affects how your brain functions. One of its key roles is supporting GABA, your brain’s main calming neurotransmitter. As progesterone levels decline, so does GABA activity, which can lead to more anxiety, irritability, and difficulty sleeping.
In the brain, progesterone is also converted into a compound called allopregnanolone. This neurosteroid plays a major role in stabilizing mood, reducing anxiety, and supporting deep, restorative sleep. Lower levels of allopregnanolone are associated with many of the classic symptoms women report in perimenopause: feeling “wired but tired,” emotional volatility, and trouble falling or staying asleep. Beyond its calming effects, progesterone may help protect brain cells from damage and support healthy memory function. Newer research shows progesterone increases brain-derived neurotrophic factor (BDNF), a protein critical for learning, memory, and long-term cognitive health.
The form of progesterone matters
Not all forms of progesterone act the same way in the body. Much of the early research on hormone replacement used synthetic progestins like medroxyprogesterone acetate (MPA), which do not fully replicate the effects of natural progesterone.
The Women’s Health Initiative (WHI) raised concerns about risks such as cardiovascular events, breast cancer, and cognitive decline. Many of these concerns have since been re-evaluated, with evidence suggesting some of the risk was related to the use of synthetic progestins like MPA, misinterpretation of the data, and to starting therapy late, well after menopause.
Unlike natural progesterone, MPA does not convert to allopregnanolone in the brain and may suppress BDNF, limiting its ability to support brain function, mood, and sleep. By contrast, oral micronized progesterone—bioidentical to the body’s own progesterone—has shown more favorable effects. A 2018 randomized trial found that women using transdermal estradiol combined with oral micronized progesterone had slower cognitive decline compared to placebo in women with mild cognitive impairment. Other studies also show better sleep, lower anxiety, and improved emotional stability with micronized progesterone compared to synthetic progestins.
A window of opportunity
For many women, perimenopause is an ideal time to evaluate and address progesterone levels. Starting progesterone support earlier—before years of poor sleep, stress, and neuroinflammation accumulate—may help protect brain function and improve quality of life long before full menopause.
Hormone replacement is never one-size-fits-all. At BioLounge, we take a comprehensive, individualized approach, incorporating advanced testing, personalized dosing, and ongoing monitoring to ensure both safety and long-term benefit.
Ready to take the next step?
If you're in your 40s and starting to experience disrupted sleep, rising anxiety, or mood changes, this may be a sign of shifting progesterone. Our team at BioLounge can help assess your hormone status, review your full health picture, and develop a personalized plan that supports brain, mood, sleep, and long-term hormonal health.
References
- Frye CA, Cleveland DM, Sadarangani A, Torgersen JK. Progesterone Promotes Anti-Anxiety/Depressant-like Behavior and Trophic Actions of BDNF in the Hippocampus. Int J Mol Sci. 2025;26(3):1173. doi:10.3390/ijms26031173


- Maki PM, et al. Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the KEEPS-Cog Trial. J Clin Endocrinol Metab. 2018;103(5):1951–1960. doi:10.1210/jc.2017-02113


- Prior JC, Hitchcock CL. Progesterone for Vasomotor Symptoms: A Placebo-Controlled Randomized Trial. Menopause. 2014;21(9):950-956. doi:10.1097/GME.0000000000000194


- Pinkerton JV, Santoro N. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women. Menopause. 2020;27(5):526-531. doi:10.1097/GME.0000000000001502