Hormone Biomarkers: DHEA-S

Optimal Takeaways

DHEA-S is the active form of DHEA, a cholesterol-based steroid hormone that acts as a precursor to testosterone and estrogen. 

Additional functions include immunomodulation; neurosteroid activity; bone, muscle, and skin support; anti-inflammatory effects; and reduction of vascular tension.

Levels peak between the ages of 15 and 39. Decreasing levels thereafter are associated with muscle and bone loss, atherosclerosis, immune decline, cognitive impairment, and mood imbalance. Low levels may also be seen with critical illness, hyperglycemia, cardiovascular risk, and non-alcoholic fatty liver disease. High levels can be seen with adrenal carcinoma and PCOS.

Standard Range:

Male 50 - 690 ug/dL (1.36 - 18.73 umol/L)

Female 18 - 390 ug/dL (0.49 - 10.53 umol/L)

The ODX Range:

Male 350 - 690 ug/dL (9.5 - 18.73 umol/L)

Female 275 - 390 ug/dL (7.42 - 10.53 umol/L)         

Low levels of DHEA-S can be seen with steroid use (Pagana 2021), adrenal suppression, adrenal insufficiency (Rutkowski 2014), critical illness, burns, coronary artery disease, rheumatoid arthritis, type 2 diabetes, hyperglycemia, insulin-resistant obesity (Kroboth 1999), diabetes risk (Brahimaj 2017), and NAFLD/MAFLD (Charlton 2008).

High levels of DHEA-S may be associated with adrenal carcinoma, adrenal hyperplasia, and polycystic ovary syndrome, also known as Stein-Leventhal syndrome (Pagana 2021). Statin drugs will significantly reduce levels in PCOS (Yang 2019).

Overview

Dehydroepiandrosterone (DHEA) is a steroid hormone produced from cholesterol via pregnenolone. It is a precursor to testosterone and estrogen and is produced locally in the testes and ovaries. It is also produced in the adrenal gland (Pagana 2021). DHEA is associated with functions beyond its precursor role.

The active sulfated form, DHEA-S, is the most abundant steroid in circulation, with concentrations peaking between 20 and 30 years of age. DHEA has immunomodulatory effects, supports bone density, functions as a neurosteroid, and improves muscle strength and skin integrity. It also has anti-inflammatory effects and reduces vascular tension, reducing risk of cardiac complications. Low levels are correlated with increased all-cause mortality and cardiovascular risk (Rutkowski 2014).

Blood levels of DHEA-S usually peak at age 15-39 in males and 15-29 in females and decline thereafter. Age-related decline is associated with sarcopenia, osteopenia, atherosclerosis, immunosenescence, and mood and cognitive impairment. Research suggests a role for DHEA supplementation with 25-50 mg/day in cardiovascular disease, adrenal insufficiency, allergy, inflammatory bowel disease, menopause, and infertility. Research indicates that supplementation can restore blood levels to those of young adults (Rutkowski 2014).

Meta-analysis of 42 studies demonstrates that DHEA supplementation significantly increased serum testosterone in both men and women, especially at a dose of greater than 50 mg/day for more than 12 weeks (Li 2020). DHEA supplementation may need to be restricted or avoided in hormone-dependent cancers or during hormone or anti-hormone therapy.

Circulating DHEA and DHEA-S may serve as biomarkers of stress. Levels increase during acute stress in what is believed to be a protective measure to counteract cortisol. However, this ability appears to decline with age (Dutheil 2021, Lennartsson 2012).

During prolonged stress or traumatic injury, adrenal production of anabolic DHEA-S decreases while production of catabolic cortisol increases. Researchers suggest that DHEA supplementation may be able to restore the balance of cortisol to DHEA-S and improve healing, bone remodeling, well-being, and mood as seen in other settings such as adrenal insufficiency, aging, and menopause. Research in older individuals demonstrates that an oral dose of 50 mg/day restored serum DHEA and DHEAS to levels seen in 30-year-olds (Bentley 2019).

DHEA status has also been associated with glucose regulation. Serum levels of DHEA and DHEA-S were found to be inversely associated with the risk of type 2 diabetes prospective Rotterdam Study comprising 5,189 middle-aged or older subjects. The association was sustained following adjustment for gender, age, fasting insulin and glucose, and BMI (Brahimaj 2017).

Clinical research has yielded mixed results regarding the association between DHEA and glucose regulation in those with normal glucose tolerance and adrenal sufficiency. Results suggest that DHEA likely has the most dramatic effects on individuals with compromised glucose tolerance or adrenal insufficiency at baseline. (Karbowska 2013).

Earlier research suggested that insulin increases DHEA's metabolic clearance and can decrease DHEA and DHEA-S serum levels. Hyperinsulinemia and insulin-resistant obesity can increase the metabolic clearance of DHEA 2-5-fold. Research also found that hyperglycemia can reduce serum DHEA and DHEA-S independent of insulin’s action (Kroboth 1999).

References

Bentley, Conor et al. “Dehydroepiandrosterone: a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient.” Burns & trauma vol. 7 26. 2 Aug. 2019, doi:10.1186/s41038-019-0158-z

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

Kroboth, P D et al. “DHEA and DHEA-S: a review.” Journal of clinical pharmacology vol. 39,4 (1999): 327-48. doi:10.1177/00912709922007903

Lennartsson, Anna-Karin et al. “DHEA and DHEA-S response to acute psychosocial stress in healthy men and women.” Biological psychology vol. 90,2 (2012): 143-9. doi:10.1016/j.biopsycho.2012.03.003

Li, Yuanyuan et al. “A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials.” Experimental gerontology vol. 141 (2020): 111110. doi:10.1016/j.exger.2020.111110

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

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

Yang, Song et al. “The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.” Medical science monitor : international medical journal of experimental and clinical research vol. 25 590-597. 20 Jan. 2019, doi:10.12659/MSM.914128