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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).
Cognitive
Decline:
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).
Osteoporosis:
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).
Strength:
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.
REFERENCES
Azuma T, et al, The effect
of dehydroepiandosterone 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 compositionand 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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