UNDERSTANDING MENOPAUSE: A SERIES FOR WOMEN AND THE PEOPLE WHO WORK WITH THEM | POST 4
Perimenopause mood swings, brain fog, and a stress response that fires too easily are not just an estrogen story. Three separate hormones, and the brain systems they support, are shifting at once, and here is exactly what each one is doing.
In the last post we covered the three hormones everyone names first: estrogen, progesterone, and testosterone. What we did not cover is what those three hormones do once they leave their own lane. Each of them reaches into a separate brain chemical, dopamine, serotonin, or cortisol, and it is what estrogen, progesterone, and testosterone each do to those three secondary hormones, not estrogen’s decline in isolation, that produces some of what gets called a perimenopause personality change.
Estrogen’s decline is a major part of that story. It is the main driver behind the serotonin changes covered below, and a co-driver behind the dopamine changes. But it is not the whole story. Progesterone is doing its own separate work on the brain’s stress braking system, and testosterone is doing its own separate work on motivation and drive. That is part of why the specific mix of symptoms looks so different from one woman to the next: it depends on which of the three primary hormones is declining fastest for her, not only on how low her estrogen has gotten.
Serotonin: Why Some Weeks Feel Fine and Others Feel Impossible
Serotonin is the one most directly tied to estrogen, and estrogen controls it through three separate levers at once rather than one. It upregulates tryptophan hydroxylase, the enzyme that determines how much serotonin the brain can produce in the first place. It increases the density of serotonin receptors, so the signal registers once it arrives. And it slows the serotonin transporter, the mechanism that normally clears serotonin back out of the synapse, which extends how long each signal lasts. When estrogen holds steady, all three levers move together, and mood stays level. Perimenopause does not lower estrogen in a straight line; it surges and drops unpredictably, and these three levers stop moving in sync with each other. That mismatch, rather than simply less serotonin, is why the same woman can feel entirely like herself one week and unrecognizable the next.
Picture a woman who has never been what anyone would call weepy. She has sat through layoffs, difficult performance reviews, and family emergencies without so much as a wobble in her voice. Then one ordinary Tuesday, a colleague forgets to loop her into an email, or her kid rolls their eyes at breakfast, and she finds herself blinking back tears in a bathroom stall before a nine a.m. meeting, for a reason she cannot fully explain even to herself. That is not a character change. That is three serotonin levers moving out of sync in the same week.
This is frequently where the misattribution begins. A woman who has never struggled with her mental health is suddenly evaluated for new-onset depression or an anxiety disorder, and the conversation stops there. The specific hormonal mechanism behind the symptom rarely gets named, which leaves her treating the result without understanding the cause.
Dopamine: Two Hormones, One Motivation Problem
Dopamine’s perimenopause story involves two hormones working at the same time, not one. Estrogen normally suppresses an enzyme called COMT, which clears dopamine out of the prefrontal cortex once it has done its job. When estrogen becomes erratic, COMT activity becomes erratic with it, so dopamine sometimes lingers longer than it should, which can feel like being wired, overstimulated, or unable to switch off, and other times clears too quickly, which shows up as flat motivation and brain fog. Layered on top of that shift, testosterone, which fuels the brain’s reward and drive circuitry directly, has already been declining gradually since a woman’s late twenties and drops further through perimenopause. The result is a motivation system being pulled at from two directions at once, which is part of why the fog can feel so inconsistent from one day to the next rather than a steady, predictable decline.
The confidence version of this is just as recognizable. A woman who used to walk into a boardroom and take it over without a second thought starts rereading her talking points twice before a meeting she has run a hundred times before. She hesitates before raising her hand. She catches herself apologizing before she has even finished a sentence. Colleagues who have known her for a decade start quietly wondering if she has lost a step, and she is wondering the exact same thing about herself, alone, at night. Neither of them is looking at a confidence problem. They are looking at a dopamine system that two hormones are currently pulling in opposite directions.
At work, this combination is almost always read as a performance problem rather than a biological one, because nobody in the room has been given a reason to think otherwise. What looks like a woman losing her edge is, in fact, two separate hormone systems shifting in her brain at once, and it has nothing to do with her capability.
Cortisol: When the Calming Hormone Runs Out
Cortisol regulation during perimenopause is driven mainly by progesterone, not estrogen. In the brain, progesterone converts into a compound called allopregnanolone, which amplifies the calming effect of GABA, the brain’s primary braking system. As ovulation becomes irregular and progesterone production drops, allopregnanolone drops with it, and the brain loses a significant piece of its own built-in calming mechanism. Estrogen adds a second layer on top of that: research following perimenopausal women has found altered patterns of HPA axis reactivity, including a blunted morning cortisol response paired with an evening rise that should not be there, alongside greater sensitivity to stress hormones during weeks when estrogen is climbing.
The lived experience of two hormones losing their grip on the stress response at once is a nervous system that reacts to small things as though they were large ones. A missed email, a school pickup running late, or an ordinary disagreement can suddenly feel disproportionately overwhelming. It is also a common contributor to waking around three in the morning wide awake, a pattern we will unpack fully in the sleep series ahead. The most common misattribution here is that a woman has simply stopped managing stress well, when the hormones that used to manage it for her are the thing that has changed.
Thyroid: The One This Series Doesn’t Cover, But Shouldn’t Be Ignored
Estrogen, progesterone, and testosterone are the three hormones at the centre of this series because they are the three that decline specifically as part of the menopause transition. Thyroid hormone is a separate system entirely, produced by a gland that has nothing to do with the ovaries, and it is worth naming here because its symptoms overlap so closely with everything described above. An underactive thyroid can produce fatigue, brain fog, mood changes, weight gain, and trouble regulating temperature that are very difficult to tell apart from what estrogen, progesterone, and testosterone are doing on their own.
Thyroid conditions also become more common in the same decade of life when perimenopause typically begins, and shifting estrogen levels can themselves affect thyroid hormone activity, so the two systems are genuinely capable of interacting rather than simply looking similar from the outside. If the symptoms in this post do not fully resolve once the three hormones above are addressed, or if fatigue in particular feels disproportionate to everything else, a thyroid panel is worth asking for. We will cover exactly what to ask your doctor for, and how to read the results, later in this series.
At a Glance
| Serotonin | Driven mainly by estrogen, which controls serotonin synthesis, receptor density, and reuptake speed at the same time. When those three levers stop moving together, mood swings rather than simply drops occur, often misread as new-onset depression or an anxiety disorder. |
| Dopamine | Driven jointly by estrogen, which regulates the COMT enzyme that clears dopamine from the brain, and by testosterone, which fuels motivation and reward circuitry directly and has already been declining for years. Often misread as burnout, laziness, or a career losing its shine. |
| Cortisol | Driven mainly by progesterone, whose brain metabolite allopregnanolone amplifies the calming effect of GABA, with estrogen adding a second layer through its own effect on HPA axis reactivity. Often misread as poor stress management rather than a stress response system running without its usual brakes. |
Why This Matters at Work
Menovate exists on a simple premise: employers do not fail menopausal employees out of indifference; they fail them because nobody has given them the language or the education to recognize what they are looking at. A manager who sees a normally sharp colleague become withdrawn, forgetful, or reactive has no reason to connect it to hormones unless someone has told them the connection exists. Naming these three effects, and the fact that three different hormones drive them, gives both the woman experiencing them and the people around her a more accurate story than burnout, attitude, or decline.
None of this means these symptoms are untreatable. Hormone therapy addresses the root cause for many women, and there are non-hormonal medical options for those who cannot or choose not to use it, which we cover in full in the next post, while lifestyle factors including sleep, nutrition, and movement meaningfully support all three of these systems as well.
Next week: non-hormonal medical options for the specific symptoms this post describes, for women who cannot or prefer not to use hormone therapy.
If you have questions and want to talk through it, get in touch with Aimee.
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Aimee Debow is the Founder of Menovate and a certified Menopause Coach. She appeared as a witness before the House of Commons Standing Committee on the Status of Women in June 2026. Menovate helps Canadian organizations build menopause-supportive workplaces through corporate talks, e-learning, and HR advisory services. Learn more at menovate.ca.
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