Anabolic Steroids for Controlling Weight Loss: Australian Experience, U.S. Trial

Anabolic steroids are best known to the public through the bad press
resulting from non-medical use by athletes for muscle building in
competitive sports. Unfortunately the resulting controversy has held
back legitimate medical research and use of these important drugs.
(Anabolic steroids should not be confused with corticosteroids, which
have entirely different effects.)

Recently we called Julian Gold, M.D., at the Albion Street (AIDS)
Centre, the major AIDS medical facility in Sydney, Australia, about an
unrelated subject (a dose and toxicity study of hypericin, an
antiviral). Dr. Gold also told us about the Centre's experience with a
trial of low-dose nandrolone decanoate (Deca-Durabolin), an anabolic
steroid, for preventing further loss of body weight which has no
obvious cause.

We interviewed Dr. Gold, and also called Donald Kotler, M.D., a leading
specialist in gastroenterological complications of AIDS, who is now
conducting a trial of a different but related anabolic steroid in New
York.

Interview with Julian Gold, M.D.

ATN: What patients are you treating with nandrolone decanoate (Deca-
Durabolin)?

JG: We started to use this drug two years ago, at first with patients
at very late stages of HIV infection, who had lost considerable body
weight, 15 to 20 percent or more. We treated over 30 patients with the
injectable Deca Durabolin, using 50 to 100 mg per week. This was not
very useful, as after nine months the weight loss continued.
In the last year, we have started instead to treat people who have lost
between five and ten percent of body weight. We are now using a dose of
100 mg every two weeks.

ATN: So it's just one shot every two weeks?

JG: That's right. We have had about 50 people who have used this
regimen. The objective is to stabilize weight loss, rather than to have
these people put on large amounts of weight -- not to try to replace,
because these patients have not lost too much weight. And for this study
we chose people who can still eat, and preferably can still get at
least minimal exercise, including walking or perhaps they can still go
to the gym. We tried to pick people who were just on the precipice,
where if nothing were done they would lose a lot of weight.
We looked for patients on an adequate and nutritious diet but who still
continue to lose weight. They need to have dietary counseling first,
before entering the study, to be sure it is not a bad diet that is
causing the problem. And they must not have any obvious cause of the
weight loss, such as gastrointestinal infections, malabsorption, or
untreatable diarrhea.

ATN: Who should not use the drug for safety reasons?

JG: Underlying diabetes or other endocrine problems, or liver disease,
would be among the contraindications. But we have now monitored almost
a hundred people taking this drug, and we found no adverse effects on
liver functions or any of the blood biochemistry; in fact it has
improved hemoglobin in some people. We found no adverse effect on HIV
antigen or T- helper counts.

ATN: How long have patients been on the new regimen so far.

JG: For 12 months.

ATN: Are any women using it?

JG: Deca-Durabolin is a testosterone derivative, which could cause
problems for women. We have not used it in women, but possibly we may
try in the future. We are doing this step by step.
ATN: Do you have industry support?

JG: Our research is sponsored by Organon, a local branch of Akzo, which
is headquartered in the Netherlands. Akzo makes the drug available to
us.
ATN: What are your future plans?

JG: First, we are analyzing our existing data for publication.
So far we have only conducted a pilot study, looking at any toxicity or
problems. Now we are planning a more structured clinical trial, to give
selected people the drug for 26 weeks and monitor more test results
than before, including different measures of body composition. Then we
will move into a comparative study, possibly comparing this drug with
one of the other weight-loss treatments.

The politics of AIDS, together with the politics of anabolic steroids,
has meant that we have to go slowly. But we are optimistic; people on
the treatment feel better, their appetite improves, and we have not
noticed the potential problems like virilizing [masculinizing] effects
and excessive muscle gain, because we do not use a high dose.

ATN: Can people contact you for more information?

JG: They can contact the Albion Street (AIDS) Centre, in Sydney; phone
61-2-332-1090, fax 332-4219. They can ask for Chris Oliver our clinical
nutritionist, or ask for me.

Oxandrolone Trial in New York: Interview with Donald Kotler, M.D.
To get another perspective on the use of anabolic steroids in AIDS, we
spoke briefly with Donald P. Kotler, M.D., at St. Luke's/Roosevelt
Hospital Center in New York, who is currently running a trial of
another anabolic steroid, oxandrolone, and is familiar with the work
in Australia.

ATN: How does oxandrolone differ from the nandrolone decanoate which is
being used in Australia?

DK: Both are testosterone derivatives; they differ in strength.
Testosterone has both anabolic and androgenic (masculinizing) effects.
Because of the androgenic properties, both are largely ruled out in
women. Other drugs which have the anabolic effect without the strong
androgenic effect might be more suitable for women.

ATN: Why are anabolic steroids being tried for treating HIV?

DK: This treatment is supported by a good theory. But does the theory
work? That is what the trials are designed to find out.

We know that there are metabolic changes in some AIDS patients that
keep the body from holding onto proteins. Anabolics help the body hold
onto proteins. But will they actually benefit patients? That needs to
be shown.

Our trial compares two doses of oxandrolone to a placebo. We are
recruiting 24 patients for the four-month trial; the 7th started today.
Only one has finished so far.

We have seen no side effects at all from the treatment, and some weight
gain. We are still waiting for body-composition measurements.

ATN: Do physicians have trouble prescribing these drugs because of the
controversy around them?

DK: These are controlled drugs in the U.S.; a triplicate prescription
is required. There is abuse potential, with danger to the liver from
the high doses sometimes used by bodybuilders.

ATN: So physicians may be reluctant to prescribe these drugs, without a
clear consensus for their use.

DK: We are pushing to get the data as soon as possible. The question
is, will the experience fit the theory.

Note to potential volunteers: Dr. Kotler's trial in New York is testing
two doses of oxandrolone for the treatment of malnutrition associated
with HIV infection. One third of the volunteers will receive a placebo.
The trial lasts for four months, and followup treatment will be made
available. This trial is sponsored by Gynex Pharmaceuticals, Inc., of
Vernon Hills, Illinois.

The study includes nutritional assessments, and measurements of food
intake, muscle strength, quality of life, and immune function. There is
no cost to the volunteers.

If you believe that you are suffering from malnutrition as a result of
HIV infection and are interested in volunteering for this trial, please
call Jodi in Dr. Kotler's office, 212/523-3670.

Oxandrolone Trial for Muscle Weakness: Miami, Chapel Hill, New York
A separate but related trial of the same drug for a different use is
also being conducted by Gynex Pharmaceuticals. "A Phase II Double Blind
Placebo Controlled Study of Oxandrolone for HIV-Associated
Myopathy/Muscle Weakness" is seeking HIV- positive men 18 or older with
generalized or proximal muscle weakness. Antiretroviral treatment is
not required, but patients on any FDA-approved antiretroviral must have
been on the drug for at least eight weeks before enrollment. There are
several other entry criteria, mostly for assuring patient safety.
This trial is being conducted at three sites: the University of Miami
School of Medicine, Miami; the University of North Carolina, Chapel
Hill; and Mt. Sinai School of Medicine, New York. Twenty three
volunteers are already enrolled, of the total target enrollment of 48.
Oxandrolone is already an approved drug. If these trials are
successful, the company will obtain FDA approval to market it for the
AIDS-related uses which are now being tested.