Hypothalamic Amenorrhea, Low Estrogen, and Alzheimer’s Risk: Why Recovery Matters for Brain Health
Before we dive in, we want to give credit to the author. This was written by Cat, a graduate of our Holistic HA Practitioner (HHAP) Certification Program. Cat brings a deep understanding of the root causes of HA and is passionate about supporting women on the path to recovery through education, empowerment, and holistic strategies.
Hypothalamic Amenorrhea, Low Estrogen, and Alzheimer’s: What’s the Connection?
Alzheimer’s disease is the most common cause of dementia worldwide, and women are disproportionately affected.1,4 While many factors contribute to this risk, emerging research highlights the central role of estrogen in maintaining brain health. Estrogen is not just a reproductive hormone—it is a critical neuroprotective agent, supporting memory, learning, and neuronal survival.2 Loss of estrogen may therefore increase long-term vulnerability to Alzheimer’s.1,2
For women with hypothalamic amenorrhea (HA), these findings are particularly important. In HA, reproductive hormone production is suppressed due to chronic stress, undernutrition, or excessive exercise. This leads to prolonged low levels of estrogen and testosterone, effectively mimicking an early, hypoestrogenic state.3 The important role of estrogen in neurocognitive health suggests that living for months or years without sufficient estrogen may “prime” the brain for changes characteristic of Alzheimer’s, potentially decades before menopause would naturally occur.2 Understanding the role of these hormones in brain function highlights why recovery is so crucial—not just for fertility, but for lifelong cognitive health.
Estrogen’s Role in the Brain
Estradiol, the primary form of estrogen in premenopausal women, plays a central role in brain health. One of its most critical functions is in energy metabolism. The brain relies heavily on glucose for fuel, and estrogen helps ensures neurons receive this energy efficiently by enhancing glucose uptake and improving mitochondrial function (mitochondria are the powerhouse of the cell). Without this support, neurons—highly active cells that transmit information across the brain and body—can become underpowered and more susceptible to damage.1,2,4
Estrogen also promotes synaptic plasticity, the formation and strengthening of connections between neurons that underpin learning and memory.1,2 When estrogen is sufficient, these neural circuits remain flexible and strong; when estrogen is low, communication between neurons becomes less efficient, contributing to “brain fog” and cognitive difficulties.5
Beyond energy and connectivity, estrogen provides neuroprotection. It acts as an antioxidant, lowering oxidative stress, and regulates the brain’s immune cells, the microglia.6 By keeping inflammation in check, estrogen prevents chronic neuroinflammation, which is linked to neuronal damage and the pathology of Alzheimer’s disease. Additionally, estrogen supports neurogenesis, particularly in the hippocampus—the region most critical for memory formation and among the first to be affected in Alzheimer’s.4 High concentrations of estrogen receptors in the hippocampus and prefrontal cortex highlight how vital this hormone is for maintaining cognition and memory.2
How Low Estrogen Fuels Alzheimer’s Pathways
When estrogen levels decline, whether in menopause or HA, several protective processes are lost, leaving the brain vulnerable to neurodegenerative changes.
First, estrogen normally helps regulate amyloid precursor protein (APP) processing. When estrogen is sufficient, APP is broken down safely. Without it, more amyloid-β (Aβ) is produced—a sticky protein that accumulates into plaques, one of Alzheimer’s hallmarks. Estrogen also supports the clearance of Aβ, so deficiency accelerates plaque buildup in the brain.1,7
Second, estrogen loss diminishes anti-inflammatory protection. Chronic low estrogen increases pro-inflammatory cytokines and oxidative stress, activating pathways that damage neurons.1,6 This inflammation promotes both Aβ deposition and tau hyperphosphorylation. Tau proteins normally stabilize neurons’ internal transport systems, but when hyperphosphorylated, they misfold and form tangles, disrupting neuronal function and leading to cell death.1,8
Finally, without estrogen, neurons experience an energy deficit. The brain’s ability to use glucose efficiently declines, creating an “energy crisis” that mirrors early Alzheimer’s pathology. Neurons that are under-fueled become more fragile and prone to degeneration over time.9
Why Hypothalamic Amenorrhea Is Particularly Risky
Unlike natural menopause, which occurs in midlife, HA can create a hormone-deprived state much earlier—even in the teens, twenties, or thirties. This deprives the brain of decades of estrogen’s protective effects and exposes neurons to prolonged vulnerability.
A key factor is dual hormone loss. In HA, both estrogen and testosterone are suppressed. Testosterone, often thought of as a “male hormone,” plays a critical role in the female brain. It can be converted into estradiol within brain tissue, providing additional estrogen where it is most needed. Beyond conversion, testosterone directly promotes synapse formation, neurogenesis, and reduces amyloid-β accumulation. 10,13 Losing both hormones removes two layers of neuroprotection.
HA is also frequently accompanied by chronic stress and elevated cortisol.3 High cortisol levels are toxic to hippocampal neurons, further weakening memory and amplifying the effects of low estrogen.11 Additionally, HA’s hormonal profile mirrors that of premature ovarian insufficiency or early surgical menopause, both strongly linked to higher lifetime risk of Alzheimer’s disease.12 In this way, HA places the brain in a prematurely vulnerable state, long before natural menopause occurs.
The Takeaway: Recovery Protects More Than Fertility
Recovering from hypothalamic amenorrhea is not just about restoring menstrual cycles or fertility—it is an investment in long-term brain health. Adequate estrogen protects not only bones and cardiovascular health but also memory, learning, and overall cognitive resilience.2 Restoring normal hormone production in HA helps ensure the brain receives decades of estrogen’s neuroprotective benefits, reducing the risk of setting the stage for Alzheimer’s disease later in life.2,3
Estrogen supports synaptic plasticity, neuronal energy metabolism, and the regulation of amyloid-β and tau proteins, while dampening inflammation and oxidative stress.1 Testosterone further contributes, both by conversion to estrogen and through its own direct protective effects on neurons.10,13
In early adulthood, HA removes both estrogen and testosterone, depriving the brain of crucial defenses for decades. Recovery, therefore, is not only vital for immediate wellbeing—it is a proactive step toward protecting cognitive health for the future.
Worried about what low estrogen could mean for your long-term brain health?
If you’re navigating hypothalamic amenorrhea (HA), you’re not just facing a missing period—you may also be living in a state of low estrogen that impacts memory, focus, and even future Alzheimer’s risk. Recovery can feel overwhelming when stress, food, and exercise all play a role, but you don’t have to figure it out alone.
Through our 1:1 coaching and group programs at The HA Society, we’ll help you restore your hormones, protect your cognitive health, and get your cycle back—without the confusion and guesswork. You’ll be supported with science-backed strategies, compassionate guidance, and a community of women who get it.
Want to go even deeper? Our Holistic HA Practitioner Certification Program equips you with the knowledge and tools to both heal your own body and help other women safeguard their fertility and long-term health.
Keep Reading:
What is Hypothalamic Amenorrhea?
What Labs to Request if You Suspect Functional Hypothalamic Amenorrhea (HA)
References:
Mervosh, N., & Devi, G. (2025). Estrogen, menopause, and Alzheimer's disease: understanding the link to cognitive decline in women. Frontiers in molecular biosciences, 12, 1634302. https://doi.org/10.3389/fmolb.2025.1634302
Hara, Y., Waters, E. M., McEwen, B. S., & Morrison, J. H. (2015). Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse. Physiological reviews, 95(3), 785–807. https://doi.org/10.1152/physrev.00036.2014
Shufelt, C. L., Torbati, T., & Dutra, E. (2017). Hypothalamic Amenorrhea and the Long-Term Health Consequences. Seminars in reproductive medicine, 35(3), 256–262. https://doi.org/10.1055/s-0037-1603581
Briceno Silva, G., Arvelaez Pascucci, J., Karim, H., Kaur, G., Olivas Lerma, R., Mann, A. K., Gnanasekaran, S., & Thomas Garcia, K. D. (2024). Influence of the Onset of Menopause on the Risk of Developing Alzheimer's Disease. Cureus, 16(9), e69124. https://doi.org/10.7759/cureus.69124
Frick, K. M., Fleischer, A. W., Schwabe, M. R., Abdelazim, F. A., Sem, D. S., & Donaldson, W. A. (2025). Not your mother's hormone therapy: Highly selective estrogen receptor beta agonists as next-generation therapies for menopausal symptom relief. Hormones and behavior, 173, 105773. https://doi.org/10.1016/j.yhbeh.2025.105773
Villa, A., Vegeto, E., Poletti, A., & Maggi, A. (2016). Estrogens, Neuroinflammation, and Neurodegeneration. Endocrine reviews, 37(4), 372–402. https://doi.org/10.1210/er.2016-1007
Gandy, S., & Duff, K. (2000). Post-menopausal estrogen deprivation and Alzheimer's disease. Experimental gerontology, 35(4), 503–511. https://doi.org/10.1016/s0531-5565(00)00116-9
Weinstock, M. (2025). Role of Oxidative Stress and Neuroinflammation in the Etiology of Alzheimer’s Disease: Therapeutic Options. Antioxidants, 14(7), 769. https://doi.org/10.3390/antiox14070769
Rettberg, J. R., Yao, J., & Brinton, R. D. (2014). Estrogen: a master regulator of bioenergetic systems in the brain and body. Frontiers in neuroendocrinology, 35(1), 8–30. https://doi.org/10.1016/j.yfrne.2013.08.001
Calvo, N., & Einstein, G. (2023). Steroid hormones: risk and resilience in women's Alzheimer disease. Frontiers in aging neuroscience, 15, 1159435. https://doi.org/10.3389/fnagi.2023.1159435
Ouanes, S., & Popp, J. (2019). High Cortisol and the Risk of Dementia and Alzheimer's Disease: A Review of the Literature. Frontiers in aging neuroscience, 11, 43. https://doi.org/10.3389/fnagi.2019.00043
Kodaman P. H. (2010). Early menopause: primary ovarian insufficiency and surgical menopause. Seminars in reproductive medicine, 28(5), 360–369. https://doi.org/10.1055/s-0030-1262895
Bianchi V. E. (2022). Impact of Testosterone on Alzheimer's Disease. The world journal of men's health, 40(2), 243–256. https://doi.org/10.5534/wjmh.210175
