Why Menopause Messes with ADHD
And What We Can Do About It
Whenever I give workshops on ADHD, multiple people ask why ADHD symptoms appear, or worsen, as menopause approaches. “Is it a coincidence?” they wonder. “Is it an inevitable part of aging?” “Is this the new normal?”
These generative questions prompt an inquiry into the links between menopause, brain health, and cognition. The appearance (or worsening) of ADHD symptom in menopause is no coincidence. It’s not an inevitable part of the cognitive decline that happens with aging. And it’s definitely not the new normal.
Most of us are in touch with the way our minds, brains, and bodies function. We notice even subtle changes, especially in the realm of attention. Yet all too often, reporting a shift in cognitive functioning results in a dismissal, even from doctors who identify as menopause specialists. Their common refrain is that ADHD symptoms, brain fog, and issues with working memory have nothing to do with menopause and everything to do with aging. This can leave us questioning ourselves, searching endlessly for answers, and trying to address the issues indirectly.
But it just so happens that emerging research offers insight.
To my neurodivergent mind, one of the coolest and most innovative explosions of research began when Covid-19 intensified. Pandemic lockdowns arrested studies at countless laboratories worldwide. But research groups got creative. Many began large cohort studies with vast data pools, combined projects with other labs, or compared pre-pandemic to mid-pandemic findings to examine the impact of Covid-19 on key areas of well-being.
And some of these studies reveal new understanding about the way ADHD is linked to menopause, as well as the phases that directly precede (perimenopause) and follow (postmenopause).
One study, conducted by the U.S. Centers for Disease Control and Prevention, explored the rise in ADHD diagnoses since the onset of Covid-19. As a data source, they used people aged 5-64 enrolled in employer-sponsored health plans. They examined the percentage of study participants who filled an ADHD stimulant prescription at least once after 2020.
The study confirmed an increase in adult ADHD diagnosis and in stimulant prescriptions, particularly between 2020 and 2021. Numerous media outlets reported on it, highlighting the fact that adult women of all age groups drove the increase in new stimulant prescriptions.
Yet when I looked more closely at the data, I noticed something that no outlets reported: The largest changes occurred in participants between the ages of 50 and 54.
Because the study focused only on people insured through an employer, it overlooked 6.5 million people in the U.S. who are self-employed, many of whom purchase insurance independently. And it doesn’t include the countless women who couldn’t take the time, ar afford the fees, for a diagnosis. We can infer, then, that the uptick in ADHD diagnoses in women over 50—in other words, entering menopause—would be similarly high.
This isn’t just the case in the United States. A Finnish cohort study with more than 5.5 million participants found that new ADHD diagnoses doubled between 2020 and 2022 across all age groups. Although not the largest bump, people over 55 experienced an increase of nearly 300 percent.
What’s behind the substantial bump in ADHD in menopause, and what does it signal?
It’s not just the effects of the pandemic, or more people reaching out for treatment.
In all stages of menopause, ADHD symptoms worsen. For those without previous signs of ADHD, symptoms often emerge. And in those with a previous diagnosis, ADHD symptoms often intensify.
These changes, it turns out, are neuro-biologically driven. They occur for several reasons.
Today, I’ll focus on just one: the relationship between estrogen and dopamine (and therefore, ADHD) and how menopause affects it.
ADHD and the Neurotransmitter Dopamine
ADHD, Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental syndrome that affects executive functioning, the capacity for inhibition, and emotional regulation. (Feel free to explore my Substack’s section on neurodivergence for a deeper dive into the aspects of ADHD and how embodiment can address them.)
ADHD symptoms include:
difficulties with inhibition, including thoughts, emotions, and movements
impulsivity on cognitive, emotional, and physical levels
cognitive challenges, particularly in executive functioning
emotional dysregulation, e.g. a tendency to broadcast feelings and reactions readily
in adults, hyperactivity is often internalized and resembles busyness, restlessness, multi-tasking, and a difficulty not giving in to countless random impulses that pop into mind
challenges with sustained attention and distraction control (secondary to disinhibition)
Researchers believe that anomalies in the brain’s dopamine networks contribute to ADHD.
Studies have found that the brains and nervous systems of people with ADHD have a higher density of proteins known as dopamine transporters.
This causes a reduction in brain dopamine, which is a risk factor for ADHD. The stimulants used to treat ADHD (as well as alternatives such as antidepressants) work to increase concentrations of dopamine (and sometimes norepinephrine) in the brain.
Three types of dopamine neurons exist. Two help regulate the “go/no-go” circuits of the brain. (Go refers to motivation and action, while no-go refers to inhibition of action.) The third, newly-discovered dopamine neuron, D3, relates to movement. (You can learn more about this in this article.)
If low dopamine levels contribute to ADHD, what does menopause have to do with dopamine, and with the increase in ADHD symptoms at menopause?
Dopamine, ADHD, and the Estrogen Connection
In males, gestation seems to be the most critical period for the development of ADHD risk—due specifically, some studies show, to elevated levels of placental c-reactive protein, an inflammatory molecule.
Females1, however, experience multiple critical developmental periods significant to ADHD. Each corresponds to key reproductive life events, including puberty, pregnancy, and menopause. And each has distinct hormonal patterns relevant to dopamine and ADHD symptoms.
Although individual differences occur, estrogen appears generally protective for cognition across the menstrual cycle, and has also been implicated in emotion regulation.
Rapid changes in estrogen, particularly its decline, increase the risk for ADHD symptoms. This is because of the outsized influence that estrogen has on dopamine.
Estrogen increases dopamine synthesis. In addition, it reduces dopamine degradation, reuptake, and recapture, which makes more dopamine available to the brain. It also upregulates dopaminergic receptors.
Upregulation is a process by which a cell may increase the number or activity of protein receptors or other molecules on its surface to make it more sensitive to a hormone or drug—in this case, dopamine.
Estrogen’s effects on the brain’s dopamine system carry special importance in the prefrontal cortex (PFC), a region with high amounts of estrogen compared to other cortical areas. Here, estrogen’s impact on dopamine increases working memory, a function often compromised in ADHD.
The prefrontal cortex regulates executive functioning, working memory, inhibition, attention, planning, and emotional regulation—all of which are implicated in ADHD.
In menopausal women, estrogen also protects specific cognitive functions in the presence of stress.
Through its influence in the prefrontal cortex and other regions where dopamine is synthesized, estrogen influences motivational behaviors—for example, priming inhibition and decreasing impulsive behavior.
Perhaps the most dramatic evidence for the effects of estrogen on dopamine came from a collaboration between researchers at Yale University School of Medicine and its Departments of Psychiatry, Neurosurgery, Pharmacology and, amazingly, Obstetrics and Gynecology.
The group wanted to know why Parkinson’s Disease, which relates to loss of dopamine neurons in the brain, occurs much less often in pre-menopausal women than it does in men, and then spikes precipitously in women during and after menopause.
They removed the ovaries of female monkeys, depleting their levels of estrogen (and other reproductive hormones. Without estrogen, more than 30 percent of the dopamine neurons in the substantia nigra, a major area for dopamine production, disappeared. After one month, the cells were permanently gone. But if the researchers administered estrogen within a ten-day window, the dopamine cells regenerated.
Yale Magazine, in an article reporting the study results, stated, “Estrogen deprivation leads to the death of dopamine cells in the brain.”
As startling as the results are, what grabbed my attention almost as much was the date of its publication: December 1, 2000.
This means that knowledge of the estrogen-dopamine connection has existed, circulating throughout the scientific community, for 25 years—nearly a quarter of a century. But that knowledge hasn’t fully trickled into the medical community, let alone mainstream understanding.
Where Do We Go from Here?
Another study, this one from 2024, examined estrogen’s influence in premenopausal women at different points in the menstrual cycle.
Estrogen levels rise and fall twice during the menstrual cycle. At ovulation, the midpoint of the menstrual cycle, estrogen levels rise and then fall precipitously. The study authors found that at this midpoint, declines in estrogen may interact with or worsen increases in approach and reward behaviors (the “go” dopamine circuits), leading to hyperactivity and impulsivity.
At the end of the menstrual cycle, or menstruation, estrogen levels drop again. Here, declines in estrogen may affect or exacerbate tendencies toward social withdrawal and negative affect, leading to inattentive symptoms.
The study established that declines in estrogen affect executive functioning and inhibition, both elements of ADHD, at two key points in the cycle.
This knowledge has opened the door to the possibility of adjusting and titrating the use of stimulants for ADHD in girls in a way that matches the rise and fall of estrogen at the four different phases of the menstrual cycle (the two rises and two falls of estrogen).
In the meantime, one of the best ways to address ADHD in women before and during menopause, as both a preventive and therapeutic measure, may just be menopausal hormone therapy, or MHT.
Sources:
Since the onset of the Covid-19 pandemic, the number of people with mental health diagnoses: Mental Health Problems on the Rise in Older Adults. (2024, May 6). AARP. https://www.aarp.org/health/healthy-living/info-2024/mental-health-diagnoses-spike.html. For the original citation, see: https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/Trends%20in%20Mental%20Health%20Conditions%20-%20A%20FAIR%20Health%20White%20Paper.pdf
The study confirmed a trend ADHD diagnosis in adults, as well as a marked increase in stimulant prescriptions: Danielson, M. L. (2023). Trends in Stimulant Prescription Fills Among
Commercially Insured Children and Adults—United States, 2016–2021. MMWR. Morbidity and Mortality Weekly Report, 72. https://doi.org/10.15585/mmwr.mm7213a1
The study focused primarily on people insured through their employer, overlooking the 6.5 million people: Hammond, S. F. H. and L. A. (n.d.). Self-employment in the United States. Bureau of Labor Statistics. Retrieved September 17, 2024, from https://www.bls.gov/spotlight/2016/self-employment-in-the-united-states/
And in a Finnish cohort study conducted with more than 5.5 million participants: Auro, K., Holopainen, I., Perola, M., Havulinna, A. S., & Raevuori, A. (2024). Attention-Deficit/Hyperactivity Disorder Diagnoses in Finland During the COVID-19 Pandemic. JAMA Network Open, 7(6), e2418204. https://doi.org/10.1001/jamanetworkopen.2024.18204
Studies have found that the brains and nervous systems of people with unmedicated ADHD possess: Fusar-Poli, P., Rubia, K., Rossi, G., Sartori, G., & Balottin, U. (2012). Striatal Dopamine Transporter Alterations in ADHD: Pathophysiology or Adaptation to Psychostimulants? A Meta-Analysis. American Journal of Psychiatry, 169(3), 264–272. https://doi.org/10.1176/appi.ajp.2011.11060940
In males, gestation seems to be the most important period of ADHD risk: Shao, S., Wang, J., Huang, K., Wang, S., Liu, H., Wan, S., Yan, S., Hao, J., Zhu, P., & Tao, F. (2020). Prenatal pregnancy-related anxiety predicts boys' ADHD symptoms via placental C-reactive protein. Psychoneuroendocrinology, 120, 104797. https://doi.org/10.1016/j.psyneuen.2020.104797
And each happens to have distinct hormonal patterns relevant to the risk of ADHD: Rehbein, E., Kogler, L., Hornung, J., Morawetz, C., Bayer, J., Krylova, M., Sundström-Poromaa, I., & Derntl, B. (2021). Estradiol administration modulates neural emotion regulation. Psychoneuroendocrinology, 134, 105425. Advance online publication. https://doi.org/10.1016/j.psyneuen.2021.105425
Although pronounced individual differences are observed, estrogen appears generally protective: Rehbein, E., Kogler, L., Hornung, J., Morawetz, C., Bayer, J., Krylova, M., Sundström-Poromaa, I., & Derntl, B. (2021). Estradiol administration modulates neural emotion regulation. Psychoneuroendocrinology, 134, 105425. Advance online publication. https://doi.org/10.1016/j.psyneuen.2021.105425
Estrogen increases dopamine synthesis: Barth C, Villringer A, Sacher J. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Front Neurosci. 2015 Feb 20;9:37. doi: 10.3389/fnins.2015.00037. PMID: 25750611; PMCID: PMC4335177. See also: Jacobs E, D'Esposito M. Estrogen shapes dopamine-dependent cognitive processes: implications for women's health. J Neurosci. 2011 Apr 6;31(14):5286-93. doi: 10.1523/JNEUROSCI.6394-10.2011. PMID: 21471363; PMCID: PMC3089976.
Here, estrogen’s impact on dopamine increases working memory: Jacobs E, D'Esposito M. Estrogen shapes dopamine-dependent cognitive processes: implications for women's health. J Neurosci. 2011 Apr 6;31(14):5286-93. doi: 10.1523/JNEUROSCI.6394-10.2011. PMID: 21471363; PMCID: PMC3089976.
Estrogen also protects specific cognitive functions in the presence of stress in menopausal women: Herrera AY, Hodis HN, Mack WJ, Mather M. Estradiol Therapy After Menopause Mitigates Effects of Stress on Cortisol and Working Memory. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4457-4466. doi: 10.1210/jc.2017-00825. PMID: 29106594; PMCID: PMC5718702. See also: Morrison JH, Brinton RD, Schmidt PJ, Gore AC. Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J Neurosci. 2006 Oct 11;26(41):10332-48. doi: 10.1523/JNEUROSCI.3369-06.2006. PMID: 17035515; PMCID: PMC6674699.
Through its influence in the prefrontal cortex and other regions, including ones where dopamine: Del Río JP, Alliende MI, Molina N, Serrano FG, Molina S, Vigil P. Steroid Hormones and Their Action in Women's Brains: The Importance of Hormonal Balance. Front Public Health. 2018 May 23;6:141. doi:10.3389/fpubh.2018.00141 See also: Smith CT, Sierra Y, Oppler SH, Boettiger CA. Ovarian cycle effects on immediate reward selection bias in humans: a role for estradiol. J Neurosci. 2014 Apr 16;34(16):5468-76. doi: 10.1523/JNEUROSCI.0014-14.2014. PMID: 24741037; PMCID: PMC3988406.
Perhaps the most dramatic evidence for the effects of estrogen on dopamine came from a collaboration: Leranth C, Roth RH, Elsworth JD, Naftolin F, Horvath TL, Redmond DE Jr. Estrogen is essential for maintaining nigrostriatal dopamine neurons in primates: implications for Parkinson's disease and memory. J Neurosci. 2000 Dec 1;20(23):8604-9. doi: 10.1523/JNEUROSCI.20-23-08604.2000. PMID: 11102464; PMCID: PMC6773080.
Yale Magazine, in an article reporting the study results, stated: Estrogen deprivation associated with loss of dopamine cells. (n.d.). Retrieved September 18, 2024, from https://medicine.yale.edu/news/yale-medicine-magazine/article/estrogen-deprivation-associated-with-loss-of-dopamine-cells/
Another study, this one from 2024, established that declines in estrogen affect executive functioning and inhibition: Eng, A. G., Nirjar, U., Elkins, A. R., Sizemore, Y. J., Monticello, K. N., Petersen, M. K., Miller, S. A., Barone, J., Eisenlohr-Moul, T. A., & Martel, M. M. (2024). Attention-deficit/hyperactivity disorder and the menstrual cycle: Theory and evidence. Hormones and Behavior, 158, 105466. https://doi.org/10.1016/j.yhbeh.2023.105466
Trans men who have not had hormone therapy and still have their ovaries will experience menopause as they age