DHEA Study: Does DHEA Help or Hurt Adrenal Health?

Key Findings

DHEAS supplementation (60 mg/kg for 5 weeks) in aged female gerbils significantly increased lipofuscin granule accumulation in adrenal cells, indicating cellular aging. It decreased expression of estrogen receptors (ERα and ERβ) and key steroidogenic enzymes (CYP17 and 17βHSD), while increasing 5α-reductase activity. These changes suggest a negative feedback effect on adrenal cortex function, impairing steroidogenesis. Critically, DHEAS did not reverse age-related adrenal dysfunction, contradicting its purported anti-adrenopause benefits. All reported molecular changes were statistically significant (p < 0.05), though exact p-values and effect sizes were not detailed in the summary.

Study Design

This was an in vivo animal study using aged female Mongolian gerbils (18 months old, equivalent to ~65 human years). Gerbils were divided into control (n = 5, no treatment) and experimental (n = 5, DHEAS-supplemented) groups. After 5 weeks of supplementation, adrenal glands underwent morphological (histology), hormonal (steroid profiling), and immunohistochemical (protein expression) analyses. The design was a controlled intervention trial with direct tissue-level assessment.

Dosage & Administration

The experimental group received 60 mg/kg body weight of DHEAS daily for 5 weeks. The summary does not specify the administration route (e.g., oral, subcutaneous), formulation, or timing relative to feeding. Dosing was weight-adjusted and consistent across the experimental group.

Results & Efficacy

DHEAS significantly elevated lipofuscin deposits (a marker of oxidative damage and aging) in adrenal cortical cells. It suppressed ERα, ERβ, CYP17, and 17βHSD expression (p < 0.05), impairing estrogen-mediated signaling and androgen/estrogen synthesis. Conversely, 5α-reductase (involved in androgen metabolism) increased (p < 0.05). No quantitative data on hormone levels (e.g., cortisol, DHEA) were provided, but the enzyme changes indicate reduced adrenal steroidogenic capacity. Efficacy for reversing age-related adrenal decline was absent; DHEAS exacerbated morphophysiological aging markers.

Limitations

The study had a very small sample size (n = 5/group), limiting statistical power and generalizability. It used gerbils, not humans, and focused solely on females, ignoring sex-specific responses. The 5-week duration may be insufficient to observe long-term effects. No dose-response analysis was conducted, and the mechanism linking DHEAS to enzyme changes remains unexplored. Hormonal outcomes (e.g., circulating DHEAS, cortisol) were not quantified, weakening functional conclusions.

Clinical Relevance

This study suggests DHEAS supplementation may harm adrenal function in aging, contradicting its use for "adrenopause" prevention. The increased lipofuscin and suppressed steroidogenic enzymes indicate accelerated cellular aging and reduced hormone production capacity. For supplement users, this implies DHEAS could worsen, not improve, age-related adrenal decline. Human applicability is uncertain due to species differences, but the findings warrant caution: DHEAS is not supported for maintaining adrenal health in aging females based on this evidence. Further research in primates or humans is essential before clinical recommendations.