DHEA for Depression and Dementia

From Center For Clinical Age Management, Inc.

Longevity Medicine
DHEA for Depression and Dementia
By Nancy Walsh
Nov 12, 2002, 8:34pm

History of Use

Few items on pharmacy or health food store shelves have been associated with as much hype and controversy as has DHEA (dehydroepiandrosterone). Popularly termed “andro” when professional baseball player Mark McGwire admitted using it while batting his record-breaking 70 home runs in 1998, DHEA is said to increase longevity, “melt away disease,” and improve strength, mood, cognition, and sexuality. Many athletes use it in expectation of increased muscle mass and strength, but it has now been banned by many organizations including the International Olympic Committee and the National Football League.

DHEA, the predominant steroid hormone secreted by the reticular zone of the adrenal cortex, is a precursor of both testosterone and estrogens. Researchers have suggested that the relative androgenic or estrogenic properties of the hormone vary with the ambient hormonal milieu, so that DHEA would have predominantly estrogenic effects in men with normal testosterone levels and androgen effects in premenopausal women (Ageing Res. Rev. 1[1]:29-41, 2002). The Endocrine Society has cautioned against its use, particularly by young people, because of potentially harmful effects on normal sex steroid secretion and absorption.

The Food and Drug Administration banned over-the-counter sale of DHEA in 1985, when it was being marketed for weight loss, and classified it as an unapproved new drug available only by prescription. A 1994 reversal once again permitted OTC marketing. It remains popular among consumers who use it for conditions ranging from obesity to sexual dysfunction.

It is popular as an antiaging remedy; the rationale is that serum DHEA levels peak in the third decade of life, the decrease at about 2% per year. Aging—and associated diseases—could reflect DHEA deficiency, advocates say, and its replacement could restore normal, youthful hormone status. Research on whether age-related lowering of DHEA levels is linked to disease states and whether supplementation is beneficial has yet to yield clear answers.

Mood and Cognition

An early randomized, placebo-controlled study of 30 patients ranging in age from 40 to 70 years found that 50 mg/day of DHEA raised blood levels to levels typical of subjects in their 20s. Patients in the active treatment group reported significant improvements in well being, including improved sleep, energy, and ability to manage stress (J. Clin. Endocrinol. Metab. 78[6]:1360-67, 1994).

In a later study, 60 symptomatic perimenopausal women were given 50 mg of DHEA daily or a placebo. Despite elevations in serum DHEAlevels in the active treatment group, no benefits were seen in perimenopausal symptoms, mood, libido, cognition, or memory (J. Clin. Endocrinol. Metab. 84[11]:3896-3902, 1999).

In the prospective Rotterdam Study of 189 elderly adults, the ratio of free cortisol and DHEA was linked to cognitive impairment, but supplementation was not beneficial (J. Clin. Endocrinol. Metab. 83[10]:3487-92, 1998).

There has been considerable interest in using DHEA as a neuroprotective agent in Alzheimer's disease. DHEA is thought to interact with neurotransmitter systems to promote neuronal remodeling and protect against neurotoxic insults. Its CNS activities are reported to be involved in memory consolidation, neuroprotection, and prevention of neurodegeneration (Int. Rev. Neurobiol. 46:379-97, 2001).

In a systematic review of DHEA and cognition, University of Cambridge (England) psychiatrists identified four studies, all 2 weeks or less in duration, in which cognition was evaluated; none of the studies found positive effects. “The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people,” they concluded (Cochrane Database Syst. Rev. 2: CD000304, 2001).

DHEA is a good example of a substance whose effects looked promising in early studies but whose promise was not borne out by placebo-controlled trials, Dr. Lon S. Schneider told this newspaper. “There have been very little [data] showing that it is useful in a meaningful way in improving cognition in dementia,” said Dr. Schneider, professor of psychiatry, neurology, and gerontology, University of Southern California, Los Angeles.

Depression

Elevations in cortisol levels are seen in depressive illness and DHEA has antiglucocorticoid properties thought to protect against potential harm from such elevations, so DHEAsupplementation has been hypothesized as being a potential treatment for depression.

A small double-blind trial found significant improvements in patients with major depression treated with 90 mg of DHEA daily. Hamilton Depression Scale ratings rose 30.5% in the DHEA group, vs. 5.3% with placebo (Am. J. Psychiatry 156[4]:646-49, 1999).

These authors suggest other potential antidepressant mechanisms, including increased serotonin levels in certain areas of the brain. Their study, they wrote, “adds to the growing body of literature indicating that hormonal dysregulation may be causally related to depressive illness and that certain hormonal treatments can have antidepressant effects.”

Safety Concerns

Of particular concern are metabolic effects, including insulin resistance, hypertension, and lowering of HDL cholesterol level, Dr. Andrew L. Stoll said at a seminar on treating mood and anxiety disorders in Southhampton, Bermuda.

“I'm not convinced yet of its safety,” said Dr. Stoll of Harvard Medical School and director of the Psychopharmacology Research Laboratory at McLean Hospital, Boston.