DHEA and Blood Glucose Regulation

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 the risk of cardiac complications. Low levels are correlated with increased all-cause mortality and cardiovascular risk (Rutkowski 2014).

The administration of DHEA has been associated with decreased insulin resistance and improved glucose tolerance.

Supplementation with 50 mg per day of DHEA significantly improved oral glucose tolerance test values in a randomized, double-blind study of 125 volunteers 65-75 years old. Results indicated that the 2-hour glucose decreased by 18 mg/dL in the first year of supplementation and 21 mg/dL with two years of DHEA supplementation. However, the improvement was only seen in those who initially had abnormal glucose tolerance, i.e., 2-hour glucose above 140 mg/dL (Weiss 2021).

A meta-analysis of 14 studies concluded that fasting plasma glucose significantly decreased with DHEA supplementation, especially in subjects 60 years and older receiving up to 50 mg/day DHEA for less than 12 weeks. No significant changes were seen in insulin levels or HOMA-IR values (Wang 2020).

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).

Lower circulating DHEA-S is also seen with metabolic/non-alcoholic fatty liver disease, a condition commonly associated with metabolic syndrome (Charlton 2008).

References

Brahimaj, Adela et al. “Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study.” Diabetologia vol. 60,1 (2017): 98-106. doi:10.1007/s00125-016-4136-8

Charlton, Michael et al. “Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease.” Hepatology (Baltimore, Md.) vol. 47,2 (2008): 484-92. doi:10.1002/hep.22063

Karbowska, Joanna, and Zdzislaw Kochan. “Effects of DHEA on metabolic and endocrine functions of adipose tissue.” Hormone molecular biology and clinical investigation vol. 14,2 (2013): 65-74. doi:10.1515/hmbci-2013-0009

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

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

Wang, Xiaoxue et al. “The influence of dehydroepiandrosterone (DHEA) on fasting plasma glucose, insulin levels and insulin resistance (HOMA-IR) index: A systematic review and dose response meta-analysis of randomized controlled trials.” Complementary therapies in medicine vol. 55 (2020): 102583. doi:10.1016/j.ctim.2020.102583

Weiss, Edward P et al. “Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans.” Aging vol. 3,5 (2011): 533-42. doi:10.18632/aging.100327