General:
DHEA has risen in popularity since its release to the market in the
mid 90's. It is a naturally occurring weak androgenic (male) steroid
hormone, produced by the adrenal glands.
Reported Effects:
It has been used for a variety of reasons including to try and
prevent aging, improve sexual function/erectile dysfunction, treat
cognitive decline, enhanced athletic performance, facilitate weight
loss, improve strength, treat osteoporosis, improve immunomodulation
for rheumatologic conditions, and treat depression.
Dose:
25 to 1600 mg per day - women treating menopause effects (hot
flashes, night sweats, etc) often do very well at a
much lower
dose - 5mg at bedtime is recommended)
Half Life:
Not clearly documented, but likely less than 2 hours. This is the
amount of time needed to eliminate or deactify half of the dose
taken.
Use to Relieve Depression?:
A recent double blind, randomized, placebo controlled study of 22
patients evaluated DHEA for outpatients diagnosed with major
depression. Patients received either DHEA (90mg), or placebo for 6
weeks. Depressive symptoms were evaluated with the Hamilton
Depression Rating Scale. Five of eleven patients receiving DHEA
improved their scores, whereas none of the placebo control group
improved their scores over the 6 week treatment period (Wolkowitz,
1999).
Could DHEA fight off Erectile Dysfunction?:
The Department of Urology at the University of Vienna, Austria
studied the efficacy of 50mg of DHEA per day in patients with
erectile dysfunction who were physiologically capable of having an
erection. 40 patients were randomized to receive 50mg DHEA or a
placebo, in a double blind fashion. They monitored patient's
response with the International Index of Erectile Function during 6
months of treatment. Treatment with DHEA was associated with
improvement in all 5 areas measured. Treatment was not associated
with any changes in Prostate Specific Antigen (PSA) levels, prostate
volumes, or urinary post void residual values (Reiter, 1999).
Would DHEA Make You Smart?:
A study conducted at the Osaka Medical Center for Cancer and
Cardiovascular Diseases studied the impact of 200mg of DHEAS
(S=sulfate) administered intravenously on seven patients with
multi-infarct dementia and 14 controls with strokes, but no
discernable dementia. At the start of the study, patients with
dementia had notably lower cerebrospinal fluid levels of DHEAS than
their matched controls. After treatment for 4 weeks, spinal fluid
levels of DHEA increased in all seven patients receiving the
supplement. Three of these patients showed improved ability to
perform daily activities and fewer emotional disturbances, and 2
patients showed improvement in electroencephalographic
(EEG-`brainwave') abnormalities associated with their dementia
(Azuma, 1999).
Does DHEA Prevent Osteoporosis (Bone Loss)?:
The Division of Adolescent/Young Adult Medicine at Harvard Medical
School conducted a study evaluating the efficacy of 50, 100, and
200mg per day of DHEA on improving bone mineral density in anorexic
women. 15 young women were enrolled in a randomized, double blind
fashion to receive 1 of the 3 doses. The effect of DHEA on bone was
measured physiologically, with resorption/deposition enzyme markers.
All treatment groups had statistically significant decreases in
markers for bone resorption, and corresponding increases in markers
for bone formation (Gordon, 1999).
Will DHEA Make You "Strong Like Bull"?:
Investigators from the Department of Reproductive Medicine, School
of Medicine, U. California San Diego conducted another study to
assess the value of DHEA in older persons. They designed a
randomized, double blind, placebo controlled, crossover study with 9
men and 10 women, to evaluate a 100mg dose for a 6 month duration
(total 12 months including crossover). They followed multiple
endocrinologic parameters, and examined body mass, knee strength,
and lumbar back strength. They noted a strength increase and body
fat reduction in men ( but not women), and an increase in total body
mass in women (but not men). They did not note any changes in bone
mineral density, lipid profiles, or cortisol levels. The study was
confounded in women by the majority of the subjects already taking
estrogen replacement therapy (Morales, 1998).
Immunomodulation:
The Division of Immunology and Rheumatology, Stanford University
Medical Center conducted a non-blinded trial of DHEA in patients
with Systemic Lupus Erythematosis (SLE). The stating dose was 50mg
per day, with stepwise increases allowed on a monthly basis. The
subjects, 23 women with mild to moderate disease, were evaluated on
a monthly basis with the SLE Disease Activity Index, and SLE
Activity Measure, and the Health Assessment Questionnaire. The
investigators noted significant improvements in all the outcome
measures at 6 months. The improvements were only weakly correlated
with the dosing level (Barry, 1998).
Similarly,
investigators from the same department conducted a prospective, open
label trial, of DHEA for 1 year in 50 women with SLE. They found
that those subjects who completed the study had improved SLE Disease
Activity Index scores, patient global assessment, and physician
global assessment scores. These benefits persisted throughout the
treatment period. Mild acne was the only reported side effect of
treatment (Van Vollenhoven, 1998).
Weight Loss:
Investigators from the Medical College of Virginia published a
prospective, double blind, placebo controlled weight loss trial.
Their treatment arm (5 men) received 1600mg of DHEA per day, for 28
days. This dose resulted in a 3 fold increase in DHEAS and a 2 fold
increase in androstenedione. At the end of treatment, the DHEA
subjects demonstrated a 31% decrease in fat mass (by
anthropometrics) with no change in total body mass. This was
probably the original study that backed the DHEA weight loss idea.
Interestingly enough, the test group also showed a 7.5% decrease in
LDL (`bad') cholesterol (Nester, 1988).
Another
randomized, double blind, placebo controlled study performed by the
Department of Pediatrics at NY Hospital-Cornell University Medical
Center studied the effect of 40mg DHEA sublingually twice per day,
in obese adolescents. Their trial ran for 8 weeks of treatment, and
failed to show any effect of DHEA on weight, at this dose (Vogiatzi,
1996).
These studies
compare a supplement close to its two known dosing extremes.
Unfortunately, few other studies have bridged the gap between these
two doses to actually define what dose of DHEA will impact body
composition, for most patients.
Pharmacology:
Oral steroid compounds are well absorbed throughout the
gastrointestinal tract, but undergo significant metabolism in the
liver. 50mg to 100mg appears to raise the serum levels of DHEA and
DHEAS in older persons to those found in younger adults. Orally
ingested DHEA is also converted to DHEAS, with a smaller fraction
being converted to androstenedione, and even smaller fraction
converted to testosterone. All these hormones modulate metabolism,
muscle mass, sex drive, behavior, as well as many other
psychological processes.
Adverse Effects:
Potential side effects include acne, irritability, increase in sex
drive, liver toxicity, increased appetite, alterations in
cholesterol, and prostate enlargement. There is a case report of
DHEA causing mania, an acute psychiatric disorder (Psychiatry Drug
Alerts, 1999). There is a theoretical risk of an increase in heart
disease and stoke, but unfortunately no long term data exists to
prove or disprove this potential complication. Most of the short
term studies cited above did not detect significant side effects
associated with treatment. Part of the low incidence of discernable
side effects likely comes from use of close-to physiologic (<200mg)
doses of DHEA in these studies. Higher doses might have a different
side effect profile (dose dependent), and warrant more careful
monitoring from your health care provider.
Discussion:
DHEA appears to be well tolerated and safe, when taken in
physiologic doses (<200mg). DHEA may have some potential benefit for
a variety of conditions. Despite improvement in study design with
the implementation of prospective double blind trials, the total
patient numbers remain small, compared to many of the studies
sponsored by pharmaceutical companies seeking FDA approval for a
specific condition. Though preliminary studies give reason for
optimism, not all studies in the literature support DHEA use, or its
efficacy. Much of this may stem from undefined dose-response data
for a specific dosing regime, in a specific patient population. No
studies have examined the tolerability of high doses of DHEA in
women, or their longer term safety profile in men.
Azuma T, et al, The effect of Dehydroepiandrosterone
sulfate administration to patients with multi-infarct dementia. J
Neurol Sci 1999 Jan 1;162(1):69-73.
Barry NN et al, Dehydroepiandrosterone in systemic
lupus erythematosus: relationship between dosage, serum levels, and
clinical response. J Rheumatol. 1998 Dec; 25(12):2352-6.
Gordon CM, et al, Changes in bone turnover markers
and menstrual function after short term oral DHEA in young women
with anorexia nervosa. J Bone Miner Res. 1999 Jan;14(1):136-45.
Morales AJ, et al, The effect of six months treatment
with 100mg daily dose of Dehydroepiandrosterone (DHEA) on
circulating sex steroids, body composition and muscle strength in
age advanced men and women. Clin Endocrinol. 1998OCT;49(4):421-32.
Nestler, JE et al, Dehydroepiandrosterone reduces
serum low density lipoprotein levels and body fat but does not alter
insulin sensitivity in normal men. J Clin Endocrinol Metab. 1988
Jan;66(1):57-61.
Reiter WJ et al, Dehydroepiandrosterone in the
treatment of erectile dysfunction: a prospective, double-blind,
randomized, placebo-controlled study. Urology. 1999 Mar;53(3):590-5
Van Vollenhoven RF et al, Treatment of systemic lupus
erythematosus with Dehydroepiandrosterone. 50 patients treated up to
12 months. J Rheumatol. 1998 Feb;25(2):285-9
Vogiatzi MG, et al. Dehydroepiandrosterone in
morbidly obese adolescents: effects on body composition, lipids, and
insulin resistance. Metabolism. 1996 Aug;45(8):1011-5.
Wolkowitz
OM, et al, double blind treatment of major depression with
Dehydroepiandrosterone. Am J Psychiatry. 1999 Apr; 156(4):646
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