Dehydroepiandrosterone (DHEA) replacement therapy may be efficacious in treating mild-to-moderate midlife depression, particularly where traditional antidepressant treatment has failed, is undesired by the patient or is not well tolerated, an expert in behavioral endocrinology reported in March. Robert J. Daly, MB, MRCPsych, senior lecturer at the Royal College of Surgeons in Ireland, described findings from a study on DHEA sponsored by the National Institute of Mental Health at the 2nd World Congress on Women's Mental Health in Washington, D.C. Daly was formerly a senior staff fellow in NIMH's Behavioral Endocrinology Branch.
While DHEA is found naturally in the body as a steroid hormone secreted by the adrenal cortex, its supplement form is extracted from the barbasco root or wild Mexican yam. In the United States, DHEA is one of the most commonly used dietary supplements, according to Daly. Supplement marketers claim it is capable of alleviating depression, slowing aging, improving memory, boosting energy and building muscle mass. Several countries, however, have banned over-the-counter (OTC) DHEA sales. Last April, the U.S. House of Representatives Energy and Commerce Committee unanimously approved the Anabolic Steroid Control Act of 2004 (HR 3866), which would make 43 steroid precursors controlled substances instead of OTC supplements, but DHEA was exempted from the list. Still, as a precaution, the bill requires the U.S. Attorney General to evaluate the health risks of dietary supplements similar to anabolic steroids not included in HR 3866 and issue a report within the next two years.
Daly said that DHEA and its sulfate metabolite, DHEA-S, are the most abundant adrenal and gonadal steroids found in humans. Dehydroepiandrosterone acts as a prohormone or hormonal precursor; specifically, it is a precursor to testosterone and estrogen.
Concentrations of DHEA are generally higher in men than women. Blood levels of DHEA and DHEA-S begin dropping when individuals are in their 20s. By the time they are in their 40s and 50s, levels of DHEA and DHEA-S have dropped by about 50%. Low DHEA levels have been associated with a variety of adverse biological consequences, including increased cardiovascular disease, decreased immune function, decreased bone density, negative lipid profile and increased fat-to-muscle ratio.
Daly, who is a consultant psychiatrist with the Beaumont Private Clinic in Dublin, Ireland, explained that a relationship between DHEA and depression has been suggested by reports of alterations (both decreases and increases) in plasma DHEA levels in depression (Jozuka et al., 2003; Young et al., 2002) and by initial reports of antidepressant-like effects of DHEA either as monotherapy or combined with traditional antidepressant agents.
"[Other researchers] have demonstrated the beneficial effects of DHEA administration, both in depressed and nondepressed men and women," Daly said. "So we carried out a study seeking to answer the following question: Is DHEA administration efficacious in treatment of midlife-onset depression?"
Daly and colleagues (2004) studied men (n=23) and women (n=23) ages 40 to 65 with midlife-onset depression. All individuals enrolled in the study met the criteria for minor or major depression. The design was a double-blind, randomized, placebo-controlled, crossover treatment study. Initially, there was a six-week screening period, following which individuals were randomized to either six weeks of DHEA treatment or placebo. Then there was a two-week washout period, followed by a crossover where individuals received a further six weeks of either DHEA or placebo. During the active phase of treatment, DHEA was administered in divided doses totaling 90 mg/day for the first three weeks, followed by doses totaling 450 mg/day for the next three weeks. The primary outcome measures included the 17-item Hamilton Rating Scale for Depression (HAM-D), Center for Epidemiologic Studies Depression Scale (CES-D) and Derogatis Sexual Functioning Inventory (DSFI). Results were analyzed by ANOVA and Bonferonni t-tests.