Hormone Deficiency in Women Over 65 and the Risk of Neurodegeneration

By Dr. Mark L. Gordon DEC 2025

Clinical Implications for Parkinson’s Disease, Multiple Sclerosis, and Dementia

As women age, their hormone levels undergo dramatic changes. After menopause, usually in the early fifties, estrogen, progesterone, testosterone, and other key hormones fall to very low levels. By the time a woman reaches 65, her body and brain have often lived decades in this hormone-deficient state.

These hormones are not just for reproduction. They are deeply involved in protecting the brain—helping neurons communicate, controlling inflammation, supporting energy production in brain cells, and even repairing damaged tissue. When levels remain chronically low, the brain becomes more vulnerable to diseases like Parkinson’s disease, multiple sclerosis (MS), and different forms of dementia, including Alzheimer’s disease and frontotemporal dementia.

This review highlights how hormone deficiency after 65 contributes to brain aging and disease, and how modern clinical approaches—including hormone replacement and advanced biomarker testing—can help reduce risk and improve quality of life.

The Aging Brain and Hormone Loss

In postmenopausal women, the ovaries stop producing estradiol and progesterone, while testosterone and DHEA also decline. Even the brain itself produces fewer neurosteroids like pregnenolone. These hormones normally act as a defense system. Estradiol improves memory circuits and helps clear toxic proteins linked to Alzheimer’s. Progesterone calms inflammation and promotes myelin repair. Testosterone and DHEA protect dopamine neurons, while pregnenolone supports overall brain plasticity and stress resilience.

Without these protective effects, women over 65 are at greater risk for cognitive decline, motor problems, and the buildup of brain damage that leads to neurodegenerative diseases.

Parkinson’s Disease

Parkinson’s disease (PD) affects both men and women, but hormones change the way it develops. Men are diagnosed more often, yet women with PD tend to decline more rapidly once the disease begins. Estrogen plays a major role in protecting dopamine-producing cells in the brain. When estrogen is low, as in older women, these cells are more vulnerable to damage from stress and toxins.

Studies suggest that women with longer lifetime exposure to estrogen—whether through later menopause or hormone replacement—are less likely to develop PD and may have milder symptoms. Other hormones also matter. Progesterone reduces brain cell loss in experimental models, while DHEA improves energy metabolism in neurons.

Clinically, this means that women over 65 with PD may benefit from carefully designed hormone restoration programs that include estrogen, progesterone, testosterone, and DHEA. Though more research is needed, the evidence points to a positive role for hormones in slowing the disease and supporting mood, energy, and thinking ability.

Multiple Sclerosis

MS is usually diagnosed in younger women, but there is a form called late-onset MS that appears after 50, and older women with MS often experience faster disability. Hormones strongly influence this disease. Pregnancy, with its high estrogen and progesterone levels, protects against MS relapses. The drop in hormones after delivery can trigger new attacks.

In older women, the permanent loss of estrogen and progesterone reduces the brain’s ability to repair myelin, the insulation around nerve fibers that is damaged in MS. Progesterone in particular helps new myelin form and reduces harmful inflammation. Estradiol supports immune balance and helps maintain healthy brain connections.

For women with MS over 65, hormone replacement could be a valuable tool. By replenishing these protective hormones, clinicians may help preserve function, reduce fatigue, and support cognition, even when standard MS drugs are already in use.

Alzheimer’s Disease

Alzheimer’s disease (AD) affects twice as many women as men, and longer life expectancy is only part of the story. Estradiol deficiency is a major factor. Without estradiol, toxic proteins like amyloid-beta and tau build up faster. At the same time, brain inflammation rises, energy production drops, and connections in memory centers weaken.

Progesterone, DHEA, and pregnenolone also play important roles in mood, memory, and stress regulation. Their loss increases the risk of Alzheimer’s. Even testosterone, though present in small amounts in women, may protect the brain from shrinkage.

Most research shows the strongest benefits when hormone replacement therapy (HRT) is started around the time of menopause. Still, new findings suggest that even in women over 65, personalized hormone strategies—such as transdermal estradiol with micronized progesterone—can help stabilize cognition and delay decline when used carefully. Combining this with DHEA supplementation, good nutrition, and regular exercise may further enhance brain protection.

Frontotemporal Dementia

Frontotemporal dementia (FTD) is less common than AD but often more disruptive, leading to personality changes, poor judgment, and language problems. Hormone research in FTD is limited, but estrogen and androgens likely help protect the frontal and temporal lobes. When these hormones decline, the brain becomes more vulnerable to damage from proteins like tau and TDP-43.

Pregnenolone and related neurosteroids, which decline steeply after 65, are important for emotional balance and flexible thinking—two areas badly affected in FTD. While hormone therapy has not yet been formally tested for FTD, restoring neurosteroid balance may improve symptoms and slow progression when combined with behavioral and supportive therapies.

Assessing Post-Menopausal Hormones

Identifying hormone deficiencies accurately is the first step toward treatment. Standard lab panels often test only a handful of hormones, missing important aspects of brain health. The Millennium 28-point biomarker panel offers a more complete view. It measures sex hormones, adrenal hormones, inflammatory markers, and metabolic indicators that together shape brain resilience.

This approach produces a personalized hormonal map, allowing treatment to be tailored to each woman’s unique needs. Rather than applying a one-size-fits-all plan, clinicians can use this data to target specific deficiencies in estradiol, progesterone, testosterone, DHEA, or pregnenolone. In this way, hormone therapy becomes safer, more precise, and more effective in protecting the brain.

In women at risk for Parkinson’s, MS, or dementia, early detection of subtle neurosteroid loss allows for proactive treatment—potentially before significant decline occurs. This represents a major step forward in personalized medicine for aging women.

Clinical Implications and Outlook

The message is clear: hormone deficiency after 65 leaves the brain more vulnerable to neurodegeneration. Estradiol, progesterone, testosterone, DHEA, and pregnenolone each play protective roles, and their combined loss increases the likelihood of Parkinson’s disease, MS progression, and dementia.

Clinicians should consider hormone restoration not just as a reproductive issue but as a neuroprotective strategy. The safest and most effective approaches involve modern delivery systems such as transdermal estradiol, natural progesterone, and carefully monitored DHEA, tailored to the individual using biomarker-guided testing.

Equally important are lifestyle measures that work hand in hand with hormones: exercise, cognitive training, balanced nutrition, and cardiovascular health management. These steps, together with precision hormone support, offer women over 65 a proactive way to maintain independence, cognition, and quality of life.

Conclusion

Women over 65 are the fastest-growing demographic at risk for neurodegenerative disease. The common thread across Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, and frontotemporal dementia is chronic hormone deficiency. By recognizing this connection and using advanced tools like the 28-point biomarker panel, clinicians can design personalized protocols that restore balance, protect the brain, and delay decline.

Hormone restoration—viewed through the lens of brain health rather than reproduction—represents one of the most hopeful strategies for preventing neurodegeneration in older women.

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