DHEA Replacement in Women with Adrenal Insufficiency
December 1, 1999 4 minutes read
DHEA Replacement in Women with Adrenal Insufficiency
Abstract & commentary
Synopsis: When given to women with documented adrenal insufficiency, the androgenic precursor DHEA improves well-being and sexuality.
Source: Arlt W, et al. N Engl J Med 1999;341: 1013-1020.
The exact physiological roles of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) remain uncertain. In humans and other primates, the adrenal glands secrete large amounts. Despite the recognition that DHEA and DHEAS are synthesized and secreted predominantly by the adrenal glands, the common practice is to replace only glucocorticoid and mineralocorticoid levels in those with either primary or secondary adrenal insufficiency. To better understand the role of DHEA in women, Arlt and colleagues performed a double-blind, placebo-controlled, crossover trial in 24 women with documented adrenal insufficiency. Women were given either DHEA 50 mg daily orally or placebo for three months, followed by a one-month wash-out period, and then three months treatment with whichever product they did not receive initially. As needed, women were on stable doses of glucocorticoids, mineralocorticoids, and gonadal steroids. Outcome measures included hormone levels, cholesterol and lipoprotein profiles, and psychometric inventories. During treatment, serum concentrations of DHEA, DHEAS, androstenedione, testosterone, and dihydrotestosterone increased to the low-normal range. Serum levels of the primary peripheral metabolite of DHEA, androstanediol glucoronide, increased to the upper limit of normal for women. Estrogen levels did not change significantly. Cholesterol levels decreased slightly, as did HDL-cholesterol during treatment with DHEA. Sense of well-being and sexuality as measured by psychometric inventories also improved during treatment with DHEA but not placebo. Five of 24 women reported androgenic side effects such as acne and increased body hair. One woman developed hair loss that resolved when the dose was decreased to 50 mg every other day.
COMMENT By Sarah L. Berga, MD
The adrenal hormone DHEA is sold in the United States as a food supplement. The common belief is that it restores declining vitality associated with normal aging. This attribution is based in part on the recognition that the adrenal production of DHEA declines steadily with advancing age. In the accompanying editorial, Oelkers points out that by age 70-80 years, the circulating levels of DHEA and its sulfate are roughly 20% of peak in men and 30% of peak in women.1 It is not surprising that DHEA is touted as an anti-aging compound. However, no long-term studies of its use have been conducted in humans, so we are left with only inferential data from short-term studies to gauge the veracity of this claim. The present study also studied only the short-term use of what was intended as a replacement dose, but the outcome variables are interesting and different from those previously studied. Also, to determine the physiological role, Arlt et al wisely studied women with adrenal insufficiency rather than those with DHEA levels that were normal for age. In the short-term, only about 20% of women given a dose of 50 mg daily by mouth experienced androgenic side effects. Given the promising data, Oelkers et al felt the data were of sufficient merit to recommend that a daily dose of 25-50 mg be given to any woman with adrenal insufficiency due to adrenal and pituitary causes.1 Women who are receiving glucocorticoids for other conditions may also develop DHEA insufficiency due to the suppressive effects. They too would be candidates for DHEA replacement.
It is important to point out that physiological replacement of DHEA would be best achieved by a transdermal patch, but such a product is not currently available and has not been studied. Compounding pharmacists can make 25 mg and 50 mg tablets or creams to be applied topically, but even creams will not mimic the physiological secretory pattern. Some of the untoward side effects of oral DHEA may be due to the oral route of administration, so we await an adequate replacement product. Arlt et al attribute the psychological benefits to the developing recognition that DHEA is a "neurosteroid" (i.e., that the brain can use DHEA as a precursor). Also, DHEA appears to alter central serotonergic action. In addition to androgenic side effects, Arlt et al caution that the long-term effect is unknown and there is some concern about using this product in women with breast cancer. Anticipated benefits, however, would include improved well-being, greater energy and increased libido, and increased bone mass and muscle strength. Both Oelkers and Arlt et al stop short, however, of recommending DHEA for the generic chemoprevention of aging.
Reference
1. Oelkers W. N Engl J Med 1999;341:1073-1074.
Which of the following is not likely to be attributable to DHEA use in women?
a. New onset of hirsutism
b. Increased libido
c. Decreased HDL-cholesterol level
d. Change in habitus
e. Loss of pubic and axillary hair
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content