ADHD, Perimenopause and Why Your Nervous System Won't Calm Down: Understanding GABA and the HPA Axis

There's a reason you feel like you're constantly braced for something. Like your nervous system is running on high alert even when nothing's actually wrong. For women with ADHD going through perimenopause, that feeling has a specific biological explanation. Two of them, actually. And understanding them changes how you see what's happening in your body.

What GABA Does and Why It Matters

GABA is the brain's main calming neurotransmitter. Think of it like a teacher in a classroom full of overexcited children. GABA's job is to quieten things down, reduce the noise, and get everything back to a manageable level.

For that to work, the teacher needs a functioning megaphone. In the brain, that megaphone is a neurosteroid called allopregnanolone, which is produced from progesterone. Allopregnanolone makes GABA receptors more sensitive and more effective. When it's present at healthy levels, the calming system works. The classroom settles.

In perimenopause, progesterone drops. When progesterone drops, allopregnanolone drops with it. The teacher's still there, but the megaphone's gone. The classroom gets louder. Anxiety increases, sleep deteriorates, emotional regulation becomes harder, and the nervous system struggles to come down from a state of activation. Research confirms that fluctuations and decline in allopregnanolone are directly linked to mood instability and heightened anxiety in perimenopausal women (Kooij et al., 2025).

For women with ADHD, this matters more than it does for neurotypical women. The ADHD brain already has lower baseline GABA activity and a more reactive nervous system. The drop in allopregnanolone removes what little buffer was there.

What the HPA Axis Is and What Happens When It Goes Wrong

The HPA axis is the brain's stress response system. HPA stands for hypothalamic-pituitary-adrenal, and it's the pathway that detects threat, releases cortisol, and gets the body ready to respond.

Think of it as a smoke alarm. In a healthy, well-calibrated system, the alarm goes off when there's genuine danger and quietens down once the threat's passed. In a dysregulated system, it goes off when you've burnt toast. It goes off at a difficult email, an unexpected plan change, a slightly raised voice. And it takes a long time to stop.

Women with ADHD have a more sensitive HPA axis. The threshold for triggering the stress response is lower, cortisol spikes faster, and the system takes longer to return to baseline. This isn't anxiety as a personality trait. It's a neurological difference in how the brain assesses and responds to threat (Dorani et al., 2021).

Perimenopause makes it worse. Oestrogen plays a role in regulating HPA reactivity. As oestrogen declines, the smoke alarm becomes even more sensitive. Cortisol stays elevated for longer. Sleep's disrupted, which raises cortisol further, which disrupts sleep further. The cycle compounds and for many women this is the point where everything that was manageable stops being manageable.

Why These Two Things Together Explain So Much

GABA keeps the nervous system calm. The HPA axis fires it up. In a well-functioning system they balance each other. In perimenopause with ADHD, both are compromised simultaneously. The calming system's lost its megaphone and the alarm system's become hypersensitive. The result is a nervous system that's chronically dysregulated, and a woman who's been told for years that she's too anxious, too sensitive, or not coping well enough.

She was coping. She just never had the right explanation for what she was coping with.

What This Means Practically

Understanding the mechanism is the first step. From there, there are real levers. HRT that restores progesterone can help restore allopregnanolone activity and reduce GABA dysregulation. Sleep is the single biggest lever for HPA regulation and prioritising it isn't a luxury. Magnesium supports GABA receptor function and is well tolerated by most people. And ADHD treatment, where appropriate, can reduce the baseline reactivity that makes the HPA axis fire so easily.

None of this is about willpower or stress management techniques that were never designed for this brain. It's about understanding the biology and getting the right support.

Your nervous system isn't broken. It's been running without the tools it needed.

References

Dorani, D., Bijlenga, D., Beekman, A.T.F., van Someren, E.J.W. and Kooij, J.J.S. (2021) 'Prevalence of hormone-related mood disorder symptoms in women with ADHD', Journal of Psychiatric Research, 133, pp. 10-15. Available at: https://doi.org/10.1016/j.jpsychires.2020.12.005

Kooij, J.J.S. et al. (2025) 'Research advances and future directions in female ADHD: the lifelong interplay of hormonal fluctuations with mood, cognition, and disease', Frontiers in Global Women's Health, 6, article 1613628. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC12277363/

Sharma, A., Goel, A., Dhayalan, J., Kamali Zare, V., Hanson, L. and Yalamanchi, S. (2023) 'The effect of hormone replacement therapy on cognition and mood', Clinical Endocrinology, 98(3), pp. 285-295. Available at: https://onlinelibrary.wiley.com/doi/10.1111/cen.14856