Can testosterone therapy in men affect Dehydroepiandrosterone (DHEA) levels?

Effect of Testosterone Therapy on DHEA Levels in Men

Testosterone therapy in men does not directly increase DHEA levels, but rather may lead to decreased DHEA levels through feedback inhibition of the hypothalamic-pituitary-adrenal axis. 1

Relationship Between Testosterone and DHEA

• DHEA (Dehydroepiandrosterone) is primarily an adrenal androgen precursor that can be metabolized in target tissues into active sex steroids, including testosterone and dihydrotestosterone (DHT) 2
• Exogenous testosterone administration exerts negative feedback effects at both the pituitary and hypothalamic levels, which can affect the production of various hormones in the steroidogenic pathway 1
• When testosterone is administered, it can suppress the hypothalamic-pituitary-gonadal axis through this negative feedback mechanism, potentially affecting adrenal androgen production including DHEA 1

Physiological Interactions

• In men, approximately 40% of the total androgen pool comes from adrenal DHEA, particularly in older men (65-75 years old) 2
• Testosterone therapy primarily aims to restore testosterone levels in hypogonadal men, but does not directly increase DHEA production 3
• DHEA serves as a precursor for both androgens and estrogens in peripheral tissues through a process called "intracrinology" - the local formation, action, and inactivation of sex steroids 2

Clinical Implications

• When evaluating men on testosterone therapy, clinicians should be aware that serum levels of testosterone and DHT are poor indicators of total androgenic activity in tissues 4
• The metabolites of DHT, such as androsterone glucuronide and androstane-3α,17β-diol glucuronide, may be more reliable markers of the total androgen pool 4
• Testosterone therapy is primarily indicated for men with primary or secondary hypogonadism caused by disorders of the hypothalamus, pituitary gland, or testes 3

Tissue-Specific Effects

• Research in animal models shows that DHEA supplementation results in varying tissue-specific levels of DHT, with some tissues showing physiological restoration while others may show no change or even supraphysiological levels 5
• This tissue-specific metabolism suggests that the relationship between exogenous testosterone and DHEA may also vary by tissue 5

Clinical Monitoring Considerations

• Current guidelines for testosterone therapy in men do not specifically recommend monitoring DHEA levels as part of standard care 3
• The primary focus of monitoring should be on testosterone levels, hematocrit, PSA (in appropriate age groups), and clinical symptoms 3
• Testosterone therapy may provide small improvements in sexual functioning and quality of life in hypogonadal men, but has little to no benefit for other common symptoms of aging 3

Common Pitfalls

• Assuming that testosterone therapy will increase all androgens, including DHEA, which is not supported by evidence 1, 4
• Failing to recognize that DHEA levels naturally decline with age, decreasing by approximately 60% by the time of equivalent female menopause, independent of testosterone therapy 2
• Using serum testosterone and DHT levels alone to assess total androgenic activity, when tissue-specific metabolism and conversion play significant roles 4, 5

In conclusion, while testosterone therapy is an established treatment for hypogonadism in men, it does not appear to increase DHEA levels and may potentially decrease them through feedback inhibition. Clinicians should focus on monitoring established parameters for testosterone therapy efficacy and safety rather than DHEA levels.