Episode # 11
The Alzheimer's Solution Revolution
#11 Testosterone, Progesterone, DHEA, and Allopregnanolone—Critical and Timely Neurosteroid Interventions in the Risk Reduction of Alzheimer’s Disease
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EPISODE 11
Summary and Audio
Welcome once again!
This is you host Ralph Sanchez and this is episode #11 here at The Alzheimer’s Solution Revolution podcast channel.
This episode will also correspond to #7 in a series—the Think Ahead podcast series.
A reminder that the Think Ahead is a 10-episode series that will be available to download after we have completed their publication here on this channel.
Today, I’ll continue with Susan Brender—a co-host who participated in many of these Think Ahead episodes that were produced a couple of years ago, and we’ll be talking more about hormones to continue where we left off in episode # 10.
In that last episode titled, “Why Low Estrogen Levels in Women is Linked to an Increased Risk for Alzheimer’s Disease”, we discussed a few salient points about the role of estrogen in aging women and the risk for Alzheimer’s disease—particularly with regard to glucose metabolism and estrogen’s function as a neuroprotective hormone—two very important points about estrogen in women’s brain health and brain aging.
And in this episode—#11, I’ll sharing a little more about estrogen metabolism and will also add some vital information about the role of progesterone in brain health, and a brief review of a progesterone metabolite—allopregnanolone.
Plus, we’ll do a brief overview of testosterone and DHEA which are also critical neurosteroids in aging individuals.
Neurosteroids are steroids or steroid hormones that are synthesized in the brain and they are vital in cognitive function.
In fact, the decline of these neurosteroids in aging is linked to impairments in learning and memory function, and the risk for neurological diseases such as late-onset Alzheimer’s disease.
Now before we begin with Susan’s intro, a reminder and a disclaimer that all of the information I share here on this channel is meant for educational purposes only.
Please consult with a physician if you feel anything is going south with regard to your health OR your brain health. which may require a medical diagnosis, attention, or treatment.
BrainDefend®
Top Takeaways
• Progesterone levels approach zero post-menopause, making it a pivotal hormone replacement option for maintaining mood, sleep regulation, and neuroprotection—factors strongly implicated in cognitive aging and in the risk late-onset Alzheimer’s disease (LOAD).
• Estrogen vs. Progesterone: While estrogen declines by 40–60%, progesterone nearly disappears. Clinical hormone replacement strategies should consider both the symptom profile and an individual’s unique metabolic landscape.
• Neurosteroids including progesterone, allopregnanolone, DHEA, pregnenolone, and testosterone, play essential roles in neuronal resilience, synaptic function, and cognitive integrity. Declines in these hormones in aging individuals are increasingly associated with pathophysiological mechanisms underlying Alzheimer’s disease.
• Allopregnanolone—major metabolite of oral progesterone may stimulate hippocampal neurogenesis and synaptic repair. This episode highlights allopregnanolone’s potential as a regenerative therapeutic candidate for mild cognitive impairment and LOAD.
• DHEA functions as a versatile prohormone; in women, it enhances androgenic and estrogenic pathways more efficiently than in men. Chronic stress–related DHEA depletion may contribute to cognitive decline.
• Testosterone therapy studies in men showed benefits in mood, cognition, and vitality. However, clinicians should monitor aromatization of testosterone into estrogen to prevent hormonal imbalance and unintended estrogenic side effects.
• Phytoestrogens such as genistein and daidzein (from soy and other plants) are briefly discussed. The capacity of phytoestrogens to modulate estrogen receptor signaling, reduce oxidative stress, and promote neuroprotection highlights their potential as therapeutic adjuncts in LOAD prevention.
• The adrenal stress assessment and the cortisol:DHEA ratio is clinically useful biomarker evaluation. Elevated cortisol with low DHEA indicates adrenal exhaustion which may provide insights regarding neurosteroid depletion and impaired cognitive function.
• Hormone metabolism—nutritional and supplemental strategies can modulate hormone metabolism toward neuroprotective and anti-carcinogenic pathways, and optimized both cognitive health and longevity.
• Fat issue (adipose) aromatization—peripheral conversion of testosterone and androstenedione to estrogen in adipose tissue affects both men and women; understanding this mechanism is essential for managing hormonal therapies in aging populations.
• Personalized monitoring and comprehensive lab evaluation with regard to neurosteroid therapies, adrenal function, and metabolic markers are a fundamental for safe and effective hormone replacement and cognitive protection strategies in patients at risk for LOAD.
Epidsode 11
Timestamp Highlights
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In this Episode
[01:57] Introduction by Ralph—in this episode overview, he continues the hormone discussion he presented in episode #10 regarding the role of estrogen in a woman’s risk for late-onset Alzheimer’s disease. In this episode, the hormone discussion focuses on neurosteroids, including progesterone, pregnenolone, allopregnanolone, testosterone, and DHEA.
[02:29] Neurosteroids defined: neurosteroids are synthesized in the brain and are essential for cognition. The decline of neurosteroid levels in aging is linked to learning/memory impairments and late-onset Alzheimer’s. Testing for neurosteroid levels in patients with cognitive impairment supports a more comprehensive evaluation of the underlying risk factors associated with Alzheimer’s dementia.
[03:21] Introduction to this episode, #11, and the Think Ahead podcast series, #7, by cohost, Susan Brender,
[05:17] Progesterone declines more dramatically than estrogen in post-menopause (approaching zero). In my clinical experience, and after reviewing the medical evidence and safety profile of progesterone therapy, progesterone hormone replacement therapy (HRT) can be highly effective and safe, and thus, progesterone may be preferred over estrogen in certain cases for HRT.
[08:18] Androgen vs estrogen metabolic cascade pathways—prohormones such as DHEA can convert to estrogen or testosterone differently in men and women. My personal and clinical experience—high-dose DHEA in a male patient did not increase testosterone, highlighting sex-specific conversion variability. Follow-up research into the topic revealed that DHEA therapy in aging men is not a reliable testosterone booster.Testing and monitoring are critical for safe supplementation.
[11:27] Testosterone and DHEA therapy in men improves mood, cognition, energy, and stamina. However, DHEA is not a reliable precursor for raising testosterone in men. In women, DHEA can modestly raise testosterone and may be an option if direct testosterone therapy not desired. Herbs and alternative interventions can optimize testosterone in men.
[11:56] Phytoestrogens and natural plant estrogens, or phytoestrogens, such as genistein and daidzein (soy-derived), may support estrogen function in a woman. Benefits of phytoestrogens include neuroprotection, antioxidant activity, and cognitive preservation. Phytoestrogens may provide an adjunctive therapy for women seeking non-pharmacologic estrogen support.
14:04] Adrenal function and hormone depletion are linked to chronic stress, which depletes DHEA and cortisol; adrenal health influences estrogen/progesterone production. Cortisol/DHEA ratio testing is highly recommended for evaluating adrenal reserve.
[15:39] Progesterone benefits include the alleviation of menopausal symptoms, including mood issues such as anxiety and sleep disturbances (oral progesterone). Note well, testing and monitoring can optimize therapy outcomes.
[16:43] Hormone metabolism: Estrogen is also metabolized into beneficial OR potentially carcinogenic metabolites. Estrogen metabolism is modifiable through diet (cruciferous vegetables) and supplements such as indole-3-carbinol and sulforaphane.
[17:53] Progesterone is metabolized into neurosteroids such as allopregnanolone. Allopregnanolone is an oral progesterone metabolite promotes neurogenesis and cognitive restoration. Topical progesterone bypasses liver metabolism and is less effective for neurosteroid generation.
[19:17] Allopregnanolone is a first-in-class regenerative therapy for mild cognitive impairment and Alzheimer’s disease. Allopregnanolone promotes neurogenesis, synaptic plasticity, and cognitive restoration. An earlier intervention therapy is more effective than later-stage therapy as you age.
[22:09] Fat tissue and aromatization—fat tissue produces estrogen via conversion of testosterone/androstenedione (aromatization). In men, monitoring testosterone therapy is critical as aromatization can lead to elevated estrogen levels. Hormone replacement therapies should include the potential for aromatization pathways.
[24:35] In my next episode, I’ll go into more detail about pregnenolone, melatonin, and DHEA. Remember that a comprehensive hormone assessment is a very important evaluation for insights into your cognitive health potential as you age.
Please listen in!
Ralph Sanchez, MTCM, CNS, D.Hom
BrainDefend®
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