The Effect of DHEA Supplementation on Symptomatic PeriMenopausal Women

abstract & commentary

Synopsis: When given to symptomatic perimenopausal women, the androgenic precursor DHEA increased well-being to the same extent as placebo.

Source: Barnhart KT, et al. J Clin Endocrinol Metab 1999;84:3896-3902.

The effect of the adrenal hormone dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) upon physiological and psychological functioning remains uncertain. DHEA and DHEA-S levels decline with age. Two months ago, I reviewed a study in which DHEA 50 mg was given orally each day to women with bonafide adrenal insufficiency. However, most people who take DHEA as a food supplement do so for ill-defined benefits such as prevention of aging or to increase sense of well-being. To better understand the role of DHEA in women without a defined adrenal endocrinopathy, Barnhart and colleagues performed a double-blind, placebo-controlled trial in 66 perimenopausal women who had symptoms of fatigue, irritability, insomnia, decreased libido, and overall decreased sense of well-being. Women were given either DHEA 50 mg daily orally or placebo for three months. Perimenopause was defined as "a previous history of regular menstrual cycles with a current status of at least 2 months of amenorrhea within the past year, but not more than 12 months of amenorrhea." Subjects were not taking any other hormonal medications and were free of defined psychiatric conditions. Several psychometric indices were used to assess memory and well-being. Outcome measures included hormone levels, cholesterol and lipoprotein profiles, and psychometric inventories. During treatment, serum concentrations of DHEA, DHEA-S, and testosterone increased in the treatment but not the placebo arm. Estrone and SHBG levels did not change significantly in either group. Total and HDL-cholesterol levels decreased slightly in both groups. Sense of well-being as measured by psychometric inventories improved during treatment with DHEA and with placebo.

COMMENT by Sarah L. Berga, MD

The adrenal hormone DHEA is sold in the United States as a food supplement and, thus, its use is not subject to federal regulation. DHEA levels in the circulation decline steadily with advancing age. By age 70-80 years, circulating levels of DHEA and its sulfate are roughly 30% of peak in women. The decline begins before menopause, roughly around age 20-25 years. It is not surprising, then, that DHEA is touted as an anti-aging compound and that its use is attractive to perimenopausal women with ill-defined symptoms that might be attributed more to aging and less to impending menopause. The present study evaluated the efficacy of DHEA in this typical population. In contrast to the prior study in which DHEA (same dose, same duration) was given to women with a defined lack of DHEA due to adrenal insufficiency, this study found that DHEA use was not better than placebo. Both groups improved somewhat. Barnhart et al attribute the improvement to the attention the subjects received from medical personnel while participating. No particular toxicities or deleterious side effects were attributable to DHEA use, but the duration of use was only three months.

What can one conclude about DHEA use? A daily 50-mg dose is not likely to help a perimenopausal woman who does not have a defined adrenal endocrinopathy. However, the same dose is likely to help women with documented adrenal insufficiency due to adrenal and pituitary causes. Women who are receiving glucocorticoids for other conditions are likely to develop DHEA insufficiency due to the suppressive effects of the steroids. They too would be candidates for DHEA use. In fact, the use of DHEA follows customary rules for hormone use in general, which is that the use of a hormone is indicated when there is a definable deficiency. The nonspecific use of any hormone as panacea for life’s vagaries is to be avoided.

The present study raises some important questions that the study design does not address. First, what was the cause of the reduced quality-of-life in the study population? Could the reduction have been due to the characteristic "hormonal chaos" of perimenopausal ovarian function? No effort was made to define a link between ovarian function during the study and symptoms. Was the perceived lack of quality-of-life due to psychosocial events? These also were not assessed. In reading the study, it struck me that it would be interesting to do a side-by-side randomized comparison of low-dose oral contraceptives vs. antidepressants vs. DHEA in this population to determine if any one of these options was better than medical attention or placebo alone. As both the current and previous authors noted, DHEA is a known "neurosteroid" and seems to alter central serotonergic action, so it is reasonable to think it might improve well-being, but in the absence of a defined endocrine deficiency, no benefit has yet been demonstrated.

Which of the following groups is least likely to benefit from a daily dose of 50 mg of DHEA?

a. Women taking high dose glucocorticoids for asthma

b. Women with Addison’s disease (adrenal insufficiency)

c. Women with Sheehan’s disease (pituitary apoplexy)

d. Perimenopausal women with reduced quality-of-life

e. Women taking glucocorticoids for Crohn’s disease (inflammatory bowel disease)