ADHD, serotonin and perimenopause: why an ordinary bad day can suddenly feel unbearable

If you have ever felt like an ordinary bad day suddenly became unbearable in perimenopause, and could not work out why, serotonin is a large part of the answer.

What Serotonin Actually Does

Serotonin is involved in mood regulation, sleep, appetite, and emotional resilience. When it is working well, you can absorb a difficult day without falling apart. When it is not, everything hits harder than it should.

It also plays a part in impulse control and frustration tolerance, which is part of why low serotonin can make ADHD related impulsivity and emotional reactivity feel sharper, not just lower mood on its own. Many women describe their tolerance for daily friction shrinking, the same minor setbacks that used to pass now hitting with far more force. Serotonin also has a role in how pain is perceived, which is part of why aches, joint discomfort, and a generally lower threshold for physical discomfort are so often reported alongside mood changes in perimenopause.

Why Oestrogen and Serotonin Are So Closely Linked

Oestrogen supports serotonin production and increases the sensitivity of serotonin receptors throughout the brain (Barth, Villringer and Sacher, 2015). This is why many women notice their mood is more stable in the first half of their cycle, when oestrogen is higher, and less stable in the second half, the luteal phase, when it drops.

When this pattern is severe, it is sometimes diagnosed as premenstrual dysphoric disorder. Women who are most sensitive to oestrogen's rise and fall across their monthly cycle often go on to notice the steepest mood changes in perimenopause too, since both are rooted in the same underlying sensitivity to hormonal change rather than two separate problems.

What Happens When Oestrogen Drops in Perimenopause

In perimenopause, as oestrogen declines and fluctuates, serotonin function decreases with it. Low mood, heightened anxiety, poor sleep, increased emotional reactivity, and a sense of disconnection are all consistent with reduced serotonin activity. For women with ADHD, who were already more prone to emotional dysregulation, this compounds something that was already difficult to manage.

Community studies show a one and a half to three fold greater risk of new and recurring depression in women during perimenopause compared with those who are premenopausal (Freeman et al., 2006). For women whose ADHD already made emotional regulation harder, that risk arrives on ground that was less stable to begin with.

This does not mean every woman in perimenopause develops depression, far from it. It means the hormonal environment during this transition carries a measurably higher baseline risk, on top of whatever else is already happening in someone's life or nervous system. For women managing ADHD related emotional regulation differences for their whole life already, that additional risk rarely starts from a neutral baseline.

Why This Gets Mistaken for Depression or Anxiety

So many women in perimenopause are diagnosed with depression or anxiety before anyone looks at their hormones. The symptoms overlap significantly. Low mood, anxiety, disrupted sleep, and irritability appear on the checklist for depression, anxiety, and perimenopause alike, which means a woman can describe exactly what she is feeling and still leave an appointment with only part of the picture addressed. This is less a failure of any individual doctor than a system that has historically treated hormones and mental health as separate specialities, rather than two systems constantly influencing each other.

The distinction matters, because treating serotonin deficiency with an antidepressant alone, when the underlying driver is falling oestrogen, addresses the symptom and not the cause.

What This Means Practically

HRT that restores oestrogen can support serotonin function directly, which is why it sometimes succeeds where an antidepressant alone has not (Sharma et al., 2023). Sleep, which is disrupted by both low serotonin and low oestrogen, is worth prioritising with the same seriousness as any other treatment. Movement and regular daylight exposure also support serotonin production, not as a replacement for medical treatment but alongside it. Neither will undo a genuine hormonal shortfall on its own, but both give an already stretched system a little more to work with. And if you are already taking an antidepressant and it does not feel like it is fully working, that is worth raising with your doctor as a hormone question, not only a dosage one. Tracking your mood alongside your cycle, even loosely, can also be useful evidence to bring into that conversation, since a pattern that consistently dips around hormonal transitions tells a different story to a doctor than mood that has declined for no apparent reason.

Plenty of women in this position get handed an antidepressant before anyone asks a single question about their hormones. 

References

Barth, C., Villringer, A. and Sacher, J. (2015) 'Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods', Frontiers in Neuroscience, 9, p.37. Available at:https://doi.org/10.3389/fnins.2015.00037

Freeman, E.W., Sammel, M.D., Lin, H. and Nelson, D.B. (2006) 'Associations of hormones and menopausal status with depressed mood in women with no history of depression', Archives of General Psychiatry, 63(4), pp. 375-382. Available at:https://pubmed.ncbi.nlm.nih.gov/16585466/

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