DHEA and Testosterone for Cognitive Decline and Dementia

DHEA and testosterone play many important roles in health and mental health.

Dehydroepiandrosterone (DHEA) is a ‘prohormone’ or precursor of testosterone and other hormones that occur naturally in the body. DHEA plays many important roles in the body and brain including modulation of cognition, memory, appetite, immune function, cardiovascular function, and sexual behavior. Accumulating research findings have established that DHEA has neuroprotective, antioxidant, and anti-inflammatory effects in the brain; promotes growth of new neurons (i.e. neurogenesis) and increases the synthesis and release of the neurotransmitters norepinephrine and dopamine (Martinez-Mota 2017). Blood levels of DHEA gradually decline with aging until it reaches its lowest level in the seventh decade, resulting in a variety of physiological, mental, and emotional problems such as reduced stamina, memory problems, and decline in sex drive. In this post, I briefly review the evidence for DHEA as a treatment of age-related memory loss as well as Alzheimer’s disease.

Inconsistent research findings

Although DHEA is widely used to self-treat decline in cognitive functioning associated with normal aging, research findings on the beneficial effects of DHEA on memory in both healthy and cognitively impaired adults are inconsistent (Nguyen et al 2017). A systematic review and meta-analysis found no support for DHEA as a cognitive enhancer in healthy older individuals (Evans et al 2006). The significance of findings was limited by the fact that only three studies met inclusion criteria, all studies reviewed were three months in duration or shorter, and doses tested ranged between 25 and 50 mg only.

In a six-month placebo-controlled study, male patients with Alzheimer’s disease (AD) were randomized to DHEA 50 mg twice daily vs. placebo. At three months, the DHEA group showed a trend toward superior cognitive performance compared to the placebo group and this trend lasted until the end of the study (Wolkowitz et al 2003). In a small four-week open study, seven individuals with multi-infarct dementia who received daily intravenous administration of DHEA-S (the sulfated form of DHEA) (200 mg) exhibited significant increases in serum and cerebrospinal fluid levels of DHEA-S, improvements in activities of daily living and less frequent emotional disturbances (Azuma et al 1999).

Testosterone supplementation may improve quality of life in healthy and demented elderly

Research findings have established that lower circulating testosterone levels in older men are associated with increased risk of developing AD (Ford 2018). In a six-month, double-blind, placebo-controlled study, 16 males with AD and 22 healthy adult males were randomized to receive testosterone 75 mg (in the form of a dermal gel) versus placebo together with their usual medications (Lu et al 2006). Global quality of life improved in both the demented group and healthy controls. No significant group differences were found at the end of the study; however, mildly demented patients who received testosterone experienced less decline in visuospatial abilities.

Safety concerns

DHEA is generally safe when used at dosages that may be beneficial for cognitive function. Mild insomnia is an infrequent side effect of DHEA, which should be dosed in the morning. It is prudent to avoid DHEA when there is a history of benign prostatic hypertrophy or prostate cancer. Testosterone supplementation may increase the risk of cardiovascular disease, stroke, and prostate cancer. It is prudent to consult with your family doctor before starting DHEA or testosterone.

Bottom line

Supplementation with DHEA or testosterone may reduce symptoms of cognitive decline in healthy elderly individuals who are experiencing memory problems, and in individuals with Alzheimer’s disease; however, few studies have been done and findings are inconclusive. Large placebo-controlled studies are needed to elucidate possible cognitive enhancing benefits of DHEA for age-related memory problems, Alzheimer's disease, and vascular dementia, and to determine safe, optimal dosing strategies.