DHEA — Dehydroepiandrosterone

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DHEA — Dehydroepiandrosterone

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DHEA — Dehydroepiandrosterone

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">DHEA — Dehydroepiandrosterone</th>
</tr>
<tr>
<td class="label">Study</td>
<td>N</td>
</tr>
<tr>
<td class="label">Ravaglia et al. (2006)</td>
<td>256</td>
</tr>
<tr>
<td class="label">Nasrallah et al. (2019)</td>
<td>120</td>
</tr>
<tr>
<td class="label">GRF2004</td>
<td>58</td>
</tr>
<tr>
<td class="label">Study</td>
<td>N</td>
</tr>
<tr>
<td class="label">Sun et al. (2016)</td>
<td>89</td>
</tr>
<tr>
<td class="label">Kim et al. (2019)</td>
<td>156</td>
</tr>
<tr>
<td class="label">NCT01715810</td>
<td>30</td>
</tr>
<tr>
<td class="label">Form</td>
<td>Dose Range</td>
</tr>
<tr>
<td class="label">Oral (capsule)</td>
<td>25-100 mg</td>
</tr>
<tr>
<td class="label">Sublingual</td>
<td>10-50 mg</td>
</tr>
<tr>
<td class="label">Topical (cream)</td>
<td>5-15 mg</td>
</tr>
<tr>
<td class="label">Interaction</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">Anticoagulants (warfarin)</td>
<td>May alter metabolism</td>
</tr>
<tr>
<td class="label">Insulin/sulfonylureas</td>
<td>May affect glucose</td>
</tr>
<tr>
<td class="label">Aromatase inhibitors</td>
<td>Alters estrogen conversion</td>
</tr>
<tr>
<td class="label">DHEA supplements</td>
<td>Additive effect</td>
</tr>
</table>

...

DHEA — Dehydroepiandrosterone

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">DHEA — Dehydroepiandrosterone</th>
</tr>
<tr>
<td class="label">Study</td>
<td>N</td>
</tr>
<tr>
<td class="label">Ravaglia et al. (2006)</td>
<td>256</td>
</tr>
<tr>
<td class="label">Nasrallah et al. (2019)</td>
<td>120</td>
</tr>
<tr>
<td class="label">GRF2004</td>
<td>58</td>
</tr>
<tr>
<td class="label">Study</td>
<td>N</td>
</tr>
<tr>
<td class="label">Sun et al. (2016)</td>
<td>89</td>
</tr>
<tr>
<td class="label">Kim et al. (2019)</td>
<td>156</td>
</tr>
<tr>
<td class="label">NCT01715810</td>
<td>30</td>
</tr>
<tr>
<td class="label">Form</td>
<td>Dose Range</td>
</tr>
<tr>
<td class="label">Oral (capsule)</td>
<td>25-100 mg</td>
</tr>
<tr>
<td class="label">Sublingual</td>
<td>10-50 mg</td>
</tr>
<tr>
<td class="label">Topical (cream)</td>
<td>5-15 mg</td>
</tr>
<tr>
<td class="label">Interaction</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">Anticoagulants (warfarin)</td>
<td>May alter metabolism</td>
</tr>
<tr>
<td class="label">Insulin/sulfonylureas</td>
<td>May affect glucose</td>
</tr>
<tr>
<td class="label">Aromatase inhibitors</td>
<td>Alters estrogen conversion</td>
</tr>
<tr>
<td class="label">DHEA supplements</td>
<td>Additive effect</td>
</tr>
</table>

Path: /therapeutics/dhea Also Known As: Dehydroepiandrosterone, DHEA-S (sulfate form), Androstenolone Chemical Formula: C_19H_28O_2 Molecular Weight: ~288 Da (DHEA), ~372 Da (DHEA-S) Class: Endogenous androgen/preandrogen

Overview

Mermaid diagram (expand to render)

DHEA is the most abundant circulating steroid hormone in humans, produced primarily by the adrenal cortex. It serves as a precursor to both androgen and estrogen hormones and has direct biological effects on multiple organ systems including the brain. DHEA levels decline dramatically with age — by approximately 80% between ages 25 and 75 — which has led to interest in supplementation for age-related conditions including neurodegeneration.

Mechanism of Action

1. Neuroprotective Effects

Anti-apoptotic signaling: DHEA activates pro-survival pathways including PI3K/Akt and MAPK/ERK[@manolopoulos2015]
Anti-glutamatergic effects: Reduces NMDA receptor-mediated excitotoxicity[@woolf2006]
BDNF modulation: Increases brain-derived neurotrophic factor expression[@prasad2012]
Amyloid interaction: Some evidence suggests direct binding to amyloid-β, reducing its toxicity[@aron2019]

2. Anti-Inflammatory Properties

NF-κB inhibition: Suppresses nuclear factor kappa-B inflammatory pathway[@du2019]
Cytokine reduction: Decreases pro-inflammatory TNF-α, IL-1β, IL-6[@morales2000]
Microglial modulation: Shifts microglia toward anti-inflammatory (M2) phenotype[@ridet2001]

3. Antioxidant Activity

Direct antioxidant: Scavenges free radicals[@olatunji2015]
Enzyme upregulation: Increases glutathione peroxidase and SOD[@svec2000]
Mitochondrial protection: Preserves mitochondrial function under stress[@charalampopoulos2008]

4. Hormonal Effects

Androgen precursor: Converts to testosterone and dihydrotestosterone[@labrie1997]
Estrogen precursor: Can convert to estrone and estradiol in peripheral tissues[@simpson2003]
Neurosteroid effects: Modulates GABA-A and NMDA receptors directly[@majewska1995]

5. Metabolic Effects

Insulin sensitivity: Improves glucose metabolism in some studies[@patel2018]
Lipid modulation: May improve lipid profiles[@valenti2019]
Body composition: Associated with lean muscle mass maintenance[@tann2006]

Evidence in Neurodegenerative Disease

Alzheimer's Disease

Parkinson's Disease

Preclinical Studies

Amyloid models: DHEA reduced amyloid burden and improved cognition in APP/PS1 mice[@wang2017]
PD models: Protected dopaminergic neurons in MPTP models[@gonzalez2015]
Tau models: Reduced tau phosphorylation in cell models[@li2018]

Dosing and Administration

Typical Dosing Protocols

Administration Considerations

Timing: Morning administration preferred (mimics circadian rhythm)
Cycling: Some protocols use 5 days on, 2 days off
DHEA-S: More stable form; longer half-life
Monitoring: Check DHEA-S serum levels periodically
Duration: Effects may take 4-8 weeks to appear

Target Serum Levels

Young adult range: 200-300 µg/dL DHEA-S (morning)
Therapeutic target: 150-250 µg/dL (age-adjusted)
Optimal: Individualize based on symptoms and labs

Safety Profile

Adverse Effects

Generally well-tolerated at doses ≤ 100 mg/day
Common: Acne, oily skin, mild hair loss (androgenic effects)
Less common: Mood changes, insomnia, headache
Rare: Liver enzyme elevation, cardiovascular effects

Contraindications

Hormone-sensitive cancers (breast, prostate)
Active liver disease
Pregnancy/breastfeeding

Drug Interactions

Androgenic Concerns

At higher doses, DHEA can convert to androgenic hormones:

Testosterone elevation: May increase DHT in prostate-sensitive tissue
Estrogen conversion: May increase estrogen in peripheral tissues
Monitoring: Check hormone panels periodically

Relevance to CBS/PSP Patient

Potential Benefits

Neuroprotection: Multiple mechanisms relevant to tauopathy

Anti-inflammatory: Addresses neuroinflammation in CBS/PSP

Mood support: May help with depression/anxiety in chronic illness

Energy: Addresses age-related decline in anabolic hormones

Cognitive support: Some evidence for cognitive benefit

Case For

Multiple neuroprotective mechanisms relevant to tauopathy
Addresses age-related hormone decline
Relatively well-tolerated at moderate doses
Easily accessible as OTC supplement
Inexpensive compared to prescription therapies

Case Against

Limited large-scale clinical trial data in CBS/PSP
Variable individual response
Androgenic side effects possible
Not FDA-approved for neurodegeneration
Requires monitoring for hormone levels

Net Assessment

Priority: Consider — DHEA supplementation may provide modest neuroprotective benefits with favorable safety profile at moderate doses (25-50 mg/day). The anti-inflammatory and neuroprotective mechanisms are relevant to tauopathy pathology. Recommend:

Baseline DHEA-S level testing
Start low (25 mg/day) and titrate based on levels
Monitor hormone panel (testosterone, estrogen) quarterly
Use if DHEA-S levels are below age-adjusted normal range

Confidence: Low-Moderate — Mechanistic rationale strong, mixed but generally positive clinical data, well-tolerated with monitoring.

Research Gaps and Future Directions

Tauopathy trials: No dedicated trials in CBS/PSP

Dosing optimization: Optimal dose for neuroprotection unclear

Biomarker studies: Correlation between DHEA levels and disease markers

Combination approaches: Synergy with other neuroprotective agents

[Testosterone](/mechanisms/testosterone-neurodegeneration-pathway) — Related hormone pathway
[Neuroinflammation](/mechanisms/neuroinflammation) — Related mechanism
[Neurotrophic factors](/therapeutics/bdnf-therapies) — Related approach

References

[Aron et al., J. Mol. Neurosci. (2019) (2019)](https://doi.org/10.1007/s12031-019-01323-5)

[Charalampopoulos et al., J. Neurosci. (2008) (2008)](https://doi.org/10.1523/JNEUROSCI.2008-08.02548)

[Du et al., J. Neuroinflammation (2019) (2019)](https://doi.org/10.1186/s12974-019-1543-z)

[Unknown, GRF2004 Study Group, Dement. Geriatr. Cogn. Disord. (2004) (2004)](https://doi.org/10.1159/000082068)

[Gonzalez et al., Neuropharmacology (2015) (2015)](https://doi.org/10.1016/j.neuropharm.2015.04.013)

[Kim et al., J. Clin. Neurol. (2019) (2019)](https://doi.org/10.3988/jcn.2019.15.1.44)

[Labrie et al., J. Steroid Biochem. Mol. Biol. (1997) (1997)](https://doi.org/10.1016/S0960-0760(97)

[Li et al., J. Steroid Biochem. Mol. Biol. (2018) (2018)](https://doi.org/10.1016/j.jsbmb.2018.03.012)

[Manolopoulos et al., J. Steroid Biochem. Mol. Biol. (2015) (2015)](https://doi.org/10.1016/j.jsbmb.2015.03.004)

[Morales et al., Endocrinology (2000) (2000)](https://doi.org/10.1210/endo.141.3.7363)

[Majewska et al., J. Neurosci. (1995) (1995)](https://doi.org/10.1523/JNEUROSCI.15-07-05240.1995)

[Nasrallah et al., J. Clin. Psychopharmacol. (2019) (2019)](https://doi.org/10.1097/JCP.0000000000001087)

Unknown, ClinicalTrials.gov NCT01715810 (n.d.)

[Olatunji et al., Steroids (2015) (2015)](https://doi.org/10.1016/j.steroids.2015.09.005)

[Prasad et al., J. Neurosci. Res. (2012) (2012)](https://doi.org/10.1002/jnr.23061)

[Patel et al., Diabetes Metab. Syndr. (2018) (2018)](https://doi.org/10.1016/j.dsx.2018.04.010)

[Ridet et al., Glia (2001) (2001)](https://doi.org/10.1002/glia.1105)

[Ravaglia et al., Neurology (2006) (2006)](https://doi.org/10.1212/01.wnl.0000194508.40017.4e)

[Svec et al., Endocr. Res. (2000) (2000)](https://doi.org/10.1080/07435800009036052)

[Simpson et al., Ann. Endocrinol. (2003) (2003)](https://doi.org/10.1016/S0003-4266(03)

[Sun et al., J. Neurol. Sci. (2016) (2016)](https://doi.org/10.1016/j.jns.2016.01.050)

[Tann et al., J. Clin. Endocrinol. Metab. (2006) (2006)](https://doi.org/10.1210/jc.2005-2142)

[Valenti et al., Aging Clin Exp Res. (2019) (2019)](https://doi.org/10.1007/s40520-019-01171-5)

[Woolf et al., Brain Res. (2006) (2006)](https://doi.org/10.1016/j.brainres.2006.02.107)

[Wang et al., J. Alzheimers Dis. (2017) (2017)](https://doi.org/10.3233/JAD-170279)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[Purinergic Signaling Polarization Control](/hypothesis/h-0758b337) — <span style="color:#81c784;font-weight:600">0.74</span> · Target: P2RY1 and P2RX7
[Mechanosensitive Ion Channel Reprogramming](/hypothesis/h-db6aa4b1) — <span style="color:#81c784;font-weight:600">0.65</span> · Target: PIEZO1 and KCNK2
[Lipid Droplet Dynamics as Phenotype Switches](/hypothesis/h-7d4a24d3) — <span style="color:#ffd54f;font-weight:600">0.57</span> · Target: DGAT1 and SOAT1
[Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation](/hypothesis/h-856feb98) — <span style="color:#81c784;font-weight:600">0.73</span> · Target: BDNF
[Vagal Afferent Microbial Signal Modulation](/hypothesis/h-ee1df336) — <span style="color:#81c784;font-weight:600">0.71</span> · Target: GLP1R, BDNF
[Vocal Cord Neuroplasticity Stimulation](/hypothesis/h-e0183502) — <span style="color:#ffd54f;font-weight:600">0.48</span> · Target: CHR2/BDNF

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therapeutics-dhea

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kg_node_id	None
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wiki_page_id	wp-eec1de8a0c1a
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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

306

Outgoing

315

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

DHEA — Dehydroepiandrosterone

DHEA — Dehydroepiandrosterone

DHEA — Dehydroepiandrosterone

Overview

Mechanism of Action

1. Neuroprotective Effects

2. Anti-Inflammatory Properties

3. Antioxidant Activity

4. Hormonal Effects

5. Metabolic Effects

Evidence in Neurodegenerative Disease

Alzheimer's Disease

Parkinson's Disease

Preclinical Studies

Dosing and Administration

Typical Dosing Protocols

Administration Considerations

Target Serum Levels

Safety Profile

Adverse Effects

Contraindications

Drug Interactions

Androgenic Concerns

Relevance to CBS/PSP Patient

Potential Benefits

Case For

Case Against

Net Assessment

Research Gaps and Future Directions

References

💬 Discussion

📗 Cite This Artifact

DHEA — Dehydroepiandrosterone

DHEA — Dehydroepiandrosterone

DHEA — Dehydroepiandrosterone

Overview

Mechanism of Action

1. Neuroprotective Effects

2. Anti-Inflammatory Properties

3. Antioxidant Activity

4. Hormonal Effects

5. Metabolic Effects

Evidence in Neurodegenerative Disease

Alzheimer's Disease

Parkinson's Disease

Preclinical Studies

Dosing and Administration

Typical Dosing Protocols

Administration Considerations

Target Serum Levels

Safety Profile

Adverse Effects

Contraindications

Drug Interactions

Androgenic Concerns

Relevance to CBS/PSP Patient

Potential Benefits

Case For

Case Against

Net Assessment

Research Gaps and Future Directions

Related Pages

References

Related Hypotheses

💬 Discussion