DHEA Supplementation in Liver Disease: Not Recommended
I do not recommend DHEA supplementation for patients with liver disease due to lack of safety data, absence of clinical guidelines supporting its use, and theoretical concerns about hepatotoxicity and hormone-related complications.
Why DHEA Should Be Avoided
No Guideline Support or Safety Evidence
None of the major hepatology guidelines address DHEA supplementation in chronic liver disease, including the most recent 2024 EASL-EASD-EASO guidelines on metabolic liver disease 1, the 2019 EASL nutrition guidelines 1, or the 2002 osteoporosis management guidelines 1.
The absence of DHEA from comprehensive liver disease management guidelines spanning over two decades strongly suggests insufficient evidence for safety or efficacy in this population.
Theoretical Hepatotoxicity Concerns
DHEA is metabolized by the liver, and patients with chronic liver disease have demonstrated reduced hepatic content of DHEA sulphotransferase, the enzyme responsible for metabolizing DHEA and other potentially hepatotoxic steroids 2.
This enzymatic deficiency is documented across multiple liver diseases including primary biliary cirrhosis, primary sclerosing cholangitis, chronic active hepatitis, and alcoholic cirrhosis 2.
Impaired metabolism could lead to accumulation of DHEA or its metabolites, potentially worsening liver injury.
Conflicting Research Data
Research shows paradoxical associations: higher serum DHEAS levels correlate with elevated ALT in NAFLD patients 3, while lower DHEAS levels associate with advanced fibrosis in hepatitis C 4.
These contradictory findings suggest we don't understand DHEA's role in liver disease pathophysiology well enough to recommend supplementation.
One in vitro study showed DHEA protected cholangiocytes against bile acid toxicity 5, but laboratory findings cannot be extrapolated to clinical practice without human safety trials.
What IS Recommended for Hormone Deficiency in Liver Disease
For Hypogonadal Men with Cirrhosis
Transdermal testosterone can be considered in hypogonadal men with cirrhosis to improve muscle mass and bone density, but only after discussing the theoretical risk of hepatocellular carcinoma 1, 6.
The American Association for the Study of Liver Diseases (AASLD) states testosterone may be considered in select men with cirrhosis and documented low testosterone 6.
Transdermal formulations (gel or patch) are preferred over oral testosterone as they avoid hepatic first-pass metabolism 6.
For Hypogonadal Women with Liver Disease
Premenopausal women should receive transdermal estrogen replacement (with progesterone if uterus present), not testosterone or DHEA 1, 7.
Postmenopausal women with liver disease can use transdermal estrogens, which have been shown safe in primary biliary cirrhosis without adverse liver effects 1.
Critical Pitfalls to Avoid
Do not confuse DHEA with testosterone: While testosterone has limited evidence supporting cautious use in hypogonadal cirrhotic men, DHEA has no such evidence base 1, 6.
Quality control is a major concern with DHEA supplements, as different brands contain variable amounts of active ingredient 8.
DHEA is not FDA-regulated as a drug but sold as a dietary supplement, meaning no standardization or safety monitoring exists.
If a patient insists on hormone supplementation for hypogonadism, document true hypogonadism first with morning total testosterone levels using accurate assays 6, then consider guideline-supported options like transdermal testosterone (men) or estrogen (women), not DHEA.