Elevated DHEA and Metabolic Dysfunction

Dehydroepiandrosterone (DHEA) is a steroid hormone produced from cholesterol via pregnenolone. It is produced in the testes, ovaries, and adrenal glands and is a precursor to testosterone and estrogen (Pagana 2024). The vast majority of DHEA-S, the active sulfated form and most abundant steroid in circulation, is formed in the adrenal glands. However, small amounts can be produced from DHEA in the liver and small intestine (Goodarzi 2015).

DHEA helps regulate the immune system, support bone density, improve muscle strength and skin integrity, and reduce vascular tension. It also functions as a neurosteroid. DHEA levels are highest between ages 20 and 30. Insufficient DHEA levels are correlated with increased all-cause mortality and cardiovascular risk (Rutkowski 2014).

Stress can profoundly affect DHEA metabolism. Generally, DHEA production and levels increase with acute stress, especially mental stress, peaking within an hour and declining thereafter (Dutheil 2021). However, prolonged stress can blunt the DHEA response to acute stress and jeopardize its anabolic, neuroprotective, antioxidant, anti-inflammatory, anti-glucocorticoid, and regenerative effects (Lennartsson 2022).

While elevated DHEA is considered a biomarker of acute stress, the more stable DHEA-S form is more closely associated with chronic stress (Dutheil 2021).

Increased DHEA production and elevated DHEA-S levels are markers for excess adrenal precursor androgen (APA) production, which is seen in approximately 20-30% of women with polycystic ovary syndrome (PCOS). However, elevated DHEA-S is not always associated with APAs, as excess can be converted to androstenedione (A4) (Goodarzi 2015).

A prolonged elevation in DHEA may indicate metabolic dysfunction and should be examined further. Increased levels are associated with (Pagana 2024):

• ACTH excess
• Adrenal tumors
• Congenital adrenal hyperplasia (CAH)
• Deficiency in the enzymes that convert DHEA to other compounds, i.e., testosterone and estrogen
• Early-onset androgenetic alopecia (AGA) with elevated BMI or reduced SHBG (Cannarella 2020)
• PCOS, especially non-classic phenotypes B, and C (Carmina 2022)
• PTSD (DHEA counters PTSD and can improve symptoms) (Maninger 2009)
• Smoking (Dutheil 2021)

Optimal Takeaways

• High DHEA levels may be caused by enzyme deficiencies, altered androgen metabolism, acute stress,
• Elevated DHEA levels can be a biomarker of acute stress, while lower levels may indicate prolonged stress and compromised adaptation.
• The causes of persistently elevated DHEA or DHEA-S must be investigated before initiating treatment.
• Elevated DHEA and DHEA-S levels must be evaluated and treated by a qualified healthcare practitioner

References

Brighten J. PCOS and How to Lower DHEA Levels Naturally. June 2, 2023. https://drbrighten.com/pcos-how-to-lower-dhea-levels-naturally/

Cannarella, Rossella et al. “Increased DHEAS and Decreased Total Testosterone Serum Levels in a Subset of Men with Early-Onset Androgenetic Alopecia: Does a Male PCOS-Equivalent Exist?.” International journal of endocrinology vol. 2020 1942126. 12 Feb. 2020, doi:10.1155/2020/1942126

Carmina, Enrico, and Rosa Alba Longo. “Increased Prevalence of Elevated DHEAS in PCOS Women with Non-Classic (B or C) Phenotypes: A Retrospective Analysis in Patients Aged 20 to 29 Years.” Cells vol. 11,20 3255. 17 Oct. 2022, doi:10.3390/cells11203255

Dutheil, Frédéric et al. “DHEA as a Biomarker of Stress: A Systematic Review and Meta-Analysis.” Frontiers in psychiatry vol. 12 688367. 6 Jul. 2021, doi:10.3389/fpsyt.2021.688367

Goodarzi, Mark O et al. “DHEA, DHEAS and PCOS.” The Journal of steroid biochemistry and molecular biology vol. 145 (2015): 213-25. doi:10.1016/j.jsbmb.2014.06.003

Maninger, Nicole et al. “Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS).” Frontiers in neuroendocrinology vol. 30,1 (2009): 65-91. doi:10.1016/j.yfrne.2008.11.002

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 17th ed., Mosby, 2024

Lennartsson, Anna-Karin et al. “DHEA-S production capacity in relation to perceived prolonged stress.” Stress (Amsterdam, Netherlands) vol. 25,1 (2022): 105-112. doi:10.1080/10253890.2021.2024803

Rutkowski, Krzysztof et al. “Dehydroepiandrosterone (DHEA): hypes and hopes.” Drugs vol. 74,11 (2014): 1195-207. doi:10.1007/s40265-014-0259-8