Dehydroepiandrosterone (DHEA) and cortisol are two of the most abundant steroid hormones produced by the adrenal glands, serving as central regulators of the body’s response to stress. DHEA is a precursor hormone that the body converts into androgens and estrogens, while cortisol is a glucocorticoid often called the “stress hormone.” The scientific inquiry centers on whether DHEA, either naturally or through supplementation, can directly influence or lower circulating levels of cortisol. Understanding this relationship requires a detailed look at the opposing biological functions of these two powerful molecules and an examination of the findings from clinical trials. This analysis will explore the proposed mechanisms of action and what the most current research reveals about DHEA’s ability to modulate cortisol.
The Core Functions of DHEA and Cortisol
Both DHEA and cortisol originate primarily from the adrenal cortex, the outer layer of the adrenal glands situated atop the kidneys. Cortisol manages the body’s reaction to stress, regulating metabolism, blood pressure, and inflammatory responses. It is a catabolic hormone, promoting the breakdown of tissues like muscle and fat to supply energy during times of demand. Prolonged elevation of cortisol is associated with negative health outcomes, including reduced immune function and tissue degradation.
DHEA is often viewed as an anti-glucocorticoid, exhibiting effects that counteract cortisol’s powerful actions. It is a prohormone, serving as the primary raw material for producing sex hormones, such as testosterone and estrogen, in peripheral tissues. The actions of DHEA are described as anabolic, supporting tissue growth and repair, which places it in opposition to cortisol’s catabolic role. The ratio between these two hormones, specifically the cortisol-to-DHEA ratio (CDR), is considered a more accurate marker of chronic stress and overall adrenal health than the level of either hormone alone.
Proposed Mechanisms Linking DHEA and Cortisol
The biological rationale for DHEA’s potential to lower cortisol stems from its ability to exert anti-glucocorticoid effects within the body. While DHEA does not directly suppress cortisol production at the adrenal gland, it intervenes in the local activity of cortisol in specific tissues. One significant mechanism involves the enzyme 11-beta hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts inactive cortisone into active cortisol.
DHEA is theorized to indirectly increase the function of type 2 11β-HSD, an enzyme that facilitates the conversion of active cortisol back into its inactive form, cortisone. By promoting this inactivation, DHEA effectively reduces the concentration of the active stress hormone available to bind to tissue receptors. This interference is a plausible pathway through which DHEA could mitigate the adverse effects of high cortisol without directly regulating its secretion from the adrenal glands. Some research also suggests DHEA may act as an antagonist by competing with cortisol for binding sites on the glucocorticoid receptor, dampening cortisol’s signaling effects throughout the body.
What Clinical Studies Reveal About Lowering Cortisol
Clinical research provides tangible evidence that DHEA supplementation can influence circulating cortisol levels, though the effects are not universal. A systematic review and meta-analysis of randomized controlled trials found that DHEA supplementation resulted in a significant average decrease in serum cortisol concentrations. The pooled data indicated an average reduction of approximately 53.6 nanomoles per liter in circulating cortisol.
One study involving healthy older adults administered 200 mg of DHEA daily and observed a decrease in plasma cortisol concentrations, including mean and peak levels, over the treatment period. This cortisol-lowering effect was often more pronounced and sustained in women compared to men, highlighting gender differences in the hormonal response to supplementation. However, not all studies show a direct reduction in cortisol levels; some trials using lower doses (e.g., 100 mg per day for six months) found no change in cortisol concentration. In these cases, the DHEA/cortisol ratio still increased because DHEA levels were elevated, suggesting the ratio itself may be the more relevant clinical marker.
Safety Profile and Regulatory Considerations for DHEA Use
DHEA is available in the United States as a dietary supplement, meaning it is not approved by the Food and Drug Administration (FDA) for treating any specific disease, including high cortisol. Its status as a supplement means that product quality and ingredient accuracy can vary widely, and it is not subject to the same rigorous testing as pharmaceutical drugs. Because DHEA is a potent prohormone, it can increase the body’s levels of testosterone and estrogen, leading to potential side effects related to androgenic activity.
Adverse effects include acne, oily skin, hair loss, and changes in the menstrual cycle for women. Due to its ability to affect sex hormone levels, DHEA is generally contraindicated for individuals with hormone-sensitive cancers, such as prostate, breast, or ovarian cancer. Furthermore, DHEA may negatively affect cholesterol levels, specifically lowering high-density lipoprotein (HDL) or “good” cholesterol, particularly in women. Medical consultation is necessary before initiating DHEA supplementation, especially to determine appropriate dosing, which is typically in the range of 25 to 50 mg daily for replacement therapy.