INDICES> Oxymetholone in the treatment of HIV related Cachexia (2)

[Kirsten Myhr <myhr@online.no>]

INDICES> Oxymetholone in the treatment of HIV related Cachexia (2)
----------------------------------------------------------

Dear Kamamia,

I have done a medline (Pubmed) search (Weight loss and hiv) and it gave a
lot of references. Some are copied below. When I refined the search to
oxymetholone and weight loss, few references were found, indicating that
this is not a frequently used substance in this condition. Oxymetholone is
only one of a range of anabolic steroids used in wasting, be it in cancer
patients, hiv-positives or other diseases. And anabolic steroids are only
one group of substances used for wasting. The abstracts below speaks for
themselves.

Drug Saf 1997 Nov;17(5):290-302
Therapeutic options for HIV-associated bodyweight loss. A risk-benefit
analysis.
Stosor V, Roenn JV.
Department of Medicine, Northwestern University Medical School, Chicago,
Illinois, USA.

Involuntary bodyweight loss, a common complication of infection with HIV,
is an indicator of poor prognosis and decreased survival. Because of the
multifactorial pathogenesis of HIV-related wasting, emerging therapies are
directed at the multiple proposed mechanisms of involuntary bodyweight
loss. The initial evaluation and treatment of HIV-related bodyweight loss
is focused on the identification and treatment of reversible causes of
bodyweight loss, such as secondary opportunistic infections or endocrine
dysfunction. Nutritional intervention should begin in the early stages of
HIV infection and continue throughout the life of the patient. Of the
appetite stimulants, megestrol most consistently promotes bodyweight gain,
but with a predominance of fat, not lean, body mass. Anabolic therapies
such as testosterone derivatives and recombinant human growth hormone
(somatropin) stimulate the addition of lean body mass and are begin
actively researched for the treatment of HIV-associated wasting. Finally,
thalidomide, a potent inhibitor of tumour necrosis factor-alpha, is a
potentially useful therapy that is still under investigation. New research
into the treatment of HIV-related bodyweight loss is focusing on
combination therapies.
PMID: 9391773 [PubMed - indexed for MEDLINE]

Curr Infect Dis Rep 2001 Apr;3(2):183-192
Metabolic Complications of HIV and AIDS.
Strawford A, Hellerstein MK.

Nutritional problems in the patient with HIV/AIDS may include both wasting
and the more recently described lipodystrophy syndromes, which are complex
disorders of body composition and metabolism associated with antiretroviral
therapy. In this paper we review the pathophysiology and treatment options
for both wasting and lipodystrophy.
PMID: 11286661 [PubMed - as supplied by publisher]


JPEN J Parenter Enteral Nutr 1999 Nov-Dec;23(6 Suppl):S202-9
Use of growth hormone and other anabolic agents in AIDS wasting.
Mulligan K, Tai VW, Schambelan M.
Division of Endocrinology, San Francisco General Hospital, CA 94110, USA.

Body wasting and loss of lean body mass (LBM) have been associated with
increased mortality and disease progression, and reduced quality of life,
in patients with human immunodeficiency virus (HIV) infection. The failure
of nutritional therapies and, more recently, of effective viral
suppression, to consistently restore LBM has prompted investigation of the
pharmacologic use of a number of specific protein anabolic agents,
including recombinant human growth hormone (rhGH), insulin-like growth
factor I (rhIGF-I), and synthetic testosterone derivatives, such as
nandrolone decanoate, oxandrolone, and oxymetholone. In a
placebo-controlled trial, treatment with rhGH resulted in a significant and
sustained increase in weight that was accompanied by an even greater
increase in LBM and a decrease in fat, and improvement in treadmill work
output. Preliminary data suggest that short-term rhGH treatment may be
effective in mitigating weight loss in patients with secondary infections.
Open-label studies of nandrolone decanoate suggest that this injectable
agent also can increase weight and LBM. Two oral agents, oxandrolone and
oxymetholone, can increase weight, but their effects on LBM in
placebo-controlled trials have not been reported. Taken together, these
studies demonstrate that HIV-infected individuals can regain weight and LBM
under the proper therapeutic circumstances. The effects of reversal of
wasting on survival and disease progression, long-term safety, and the
potential value of these therapies in the treatment of fat redistribution
remain to be determined.
PMID: 10571456 [PubMed - indexed for MEDLINE]

Br J Nutr 1996 Jan;75(1):129-38
Oxymetholone promotes weight gain in patients with advanced human
immunodeficiency virus (HIV-1) infection.
Hengge UR, Baumann M, Maleba R, Brockmeyer NH, Goos M.
Department of Dermatology, University of Essen, Germany.

The effect of the testosterone derivative oxymetholone alone or in
combination with the H1-receptor antagonist ketotifen, which has recently
been shown to block tumour necrosis factor alpha (TNF alpha), on weight
gain and performance status in human immunodeficiency virus (HIV) patients
with chronic cachexia was evaluated in a 30-week prospective pilot study.
Thirty patients were randomly assigned to either oxymetholone monotherapy
(n 14) or oxymetholone plus ketotifen (n 16). Patients receiving treatment
were compared with a group of thirty untreated matched controls, who met
the same inclusion criteria. Body weight and the Karnofsky index, which
assesses the ability to perform activities of daily life, and several
quality-of-life variables were measured to evaluate response to therapy.
The average weight gain at peak was 8.2 (SD 6.2) kg (+ 14.5% of body weight
at study entry) in the oxymetholone group (P < 0.001), and 6.1 (SD 4.6) kg
(+10.9%) in the combination group (P < 0.005), compared with an average
weight loss of 1.8 (SD 0.7) kg in the untreated controls. The mean time to
peak weight was 19.6 weeks in the monotherapy group and 20.8 weeks in the
combination group. The Karnofsky index improved equally in both groups from
56% before to 67% after 20 weeks of treatment (P < 0.05). The quality of
life variables (activities of daily life, and appetite/nutrition) improved
in 68% (P < 0.05) and 91% (P < 0.01) of the treated patients respectively.
Oxymetholone was safe and promoted weight gain in cachectic patients with
advanced HIV-1 infection. The addition of ketotifen did not further support
weight gain. These results suggest the need for a randomized, double-blind,
placebo-controlled multicentre trial.
PMID: 8785183 [PubMed - indexed for MEDLINE]

AIDS Patient Care STDS 1999 Mar;13(3):149-52
Megestrol acetate: promises and pitfalls.
Farrar DJ.
Center for Special Studies, New York Hospital-Cornell Medical Center, New
York, USA.

Recent reports suggest that effective antiretroviral therapy, resulting in
a plasma HIV load that has been reduced to undetectable levels, may itself
prevent HIV- and opportunistic infection-associated weight loss and lead to
substantial weight gain. Although these data are encouraging, it is clear
that a significant proportion of patients will require, in addition,
specific treatment for HIV-associated wasting. Megestrol acetate, in the
dosage range of 400 to 800 mg/day, is a useful appetite stimulant for the
prevention and treatment of HIV-associated wasting, particularly in women.
Patients need to be advised of possible adverse effects and monitored
closely. Megestrol acetate stimulates weight gain mostly through an
increase in body fat and is therefore most effective in combination with a
muscle-building exercise program, where appropriate, and an anabolic agent
(steroid or growth hormone) to maintain or increase lean body mass.
PMID: 10375262 [PubMed - indexed for MEDLINE]

Ann Pharmacother 1998 Apr;32(4):446-58
HIV wasting syndrome: treatment update.
Balog DL, Epstein ME, Amodio-Groton MI.
Montefiore Medical Center, Bronx, NY 10467, USA.

OBJECTIVE: To review the pathophysiology and treatment of HIV wasting
syndrome. DATA SOURCES AND STUDY SELECTION: MEDLINE searches (January
1987-September 1997) of the English-language medical literature were
conducted. Bibliographies were also selected during a manual review. DATA
SYNTHESIS: HIV-related weight loss, often referred to as HIV wasting
syndrome, is a common manifestation of advanced HIV infection. Wasting in
HIV involves the preferential loss of lean body mass with a paradoxical
preservation of body fat. The etiology of wasting appears to be the result
of many factors, which may include decreased caloric intake, malabsorption,
alterations in energy expenditure and metabolism, cytokine effects, and
endocrine dysfunction. Pharmacologic treatment options include appetite
stimulants (e.g., dronabinol, megestrol acetate), cytokine inhibitors
(e.g., thalidomide, cyproheptadine, ketotifen, pentoxifylline, fish oil,
N-acetylcysteine), and anabolic agents (e.g., testosterone, nandrolone,
oxandrolone, recombinant human growth hormone). CONCLUSIONS: Wasting
associated with HIV has a high morbidity and mortality rate if not
adequately managed. Therapeutic strategies include appetite stimulants,
cytokine inhibitors, and growth-promoting agents. Selection of the
appropriate agent(s) depends on the underlying cause for weight loss,
adverse effects, and cost of therapy.
PMID: 9562141 [PubMed - indexed for MEDLINE]

J Acquir Immune Defic Syndr 2000 Oct 1;25 Suppl 1:S74-80
Potential interventions for HIV/AIDS wasting: an overview.
Abrams DI.
Positive Health Program, San Francisco General Hospital, University of
California, 94110, USA. dabrams@sfaids.ucsf.edu

Although the HIV wasting syndrome has become a far less common
manifestation of advanced disease since the introduction of highly active
therapies, much has been learned about a number of potential therapeutic
interventions. HIV wasting therapies are reviewed. The evaluation of some
of these treatments for management of body habitus alterations associated
with antiretroviral therapies may be appropriate.
PMID: 11126431 [PubMed - indexed for MEDLINE]

JAMA 1999 Apr 14;281(14):1282-90
Comment in:
JAMA. 1999 Apr 14;281(14):1326-7 and JAMA. 2000 Jul 12;284(2):176;
discussion 177
Resistance exercise and supraphysiologic androgen therapy in eugonadal men
with HIV-related weight loss: a randomized controlled trial.
Strawford A, Barbieri T, Van Loan M, Parks E, Catlin D, Barton N, Neese R,
Christiansen M, King J, Hellerstein MK.
Department of Nutritional Sciences, University of California, Berkeley,
USA.
CONTEXT: Repletion of lean body mass (LBM) that patients lose in human
immunodeficiency virus (HIV) infection has proved difficult. In healthy,
HIV-seronegative men, synergy between progressive resistance exercise (PRE)
and very high-dose testosterone therapy has been reported for gains in LBM
and muscle strength. OBJECTIVE: To determine whether a moderately
supraphysiologic androgen regimen, including an anabolic steroid, would
improve LBM and strength gains of PRE in HIV-infected men with prior weight
loss and whether protease inhibitor antiretroviral therapy prevents lean
tissue anabolism. DESIGN: Double-blind, randomized, placebo-controlled
trial; post hoc analysis for effect of HIV-protease inhibitor therapy
conducted from January to October 1997. SETTING: Referral center in San
Francisco, Calif. PATIENTS: Volunteer sample of 24 eugonadal men with
HIV-associated weight loss (mean, 9% body weight loss), recruited from an
AIDS clinic and by referral and by advertisement. INTERVENTION: For 8
weeks, all subjects received supervised PRE with physiologic intramuscular
testosterone replacement (100 mg/wk) to suppress endogenous testosterone
production. Randomization was between an anabolic steroid, oxandrolone, 20
mg/d, and placebo. MAIN OUTCOME MEASURES: Lean body mass, nitrogen balance
(10-day metabolic ward measurements), body weight, muscle strength, and
androgen status. RESULTS: Twenty-two subjects completed the study (1 1 per
group). Both groups showed significant nitrogen retention and increases in
LBM, weight, and strength. The mean (SD) gains were significantly greater
in the oxandrolone group than in the placebo group (5.6 [2.1] vs 3.8 [1.8]
g of nitrogen per day [P=.05]; 6.9 [1.7] vs 3.8 [2.9] kg of LBM [P=.005];
greater strength gains for various upper and lower body muscle groups by
maximum weight lifted [P = .02-.05] and dynamometry [P = .01 -.05]). The
mean (SD) high-density lipoprotein cholesterol level declined 0.25 (0.14)
mmol/L (9.8 [5.4] mg/dL) significantly in the oxandrolone group (P < .001
compared with placebo). Results were similar whether or not patients were
taking protease inhibitors. One subject in the oxandrolone group
discontinued the study because of elevated liver function test results.
CONCLUSIONS: A moderately supraphysiologic androgen regimen that included
an anabolic steroid, oxandrolone, substantially increased the lean tissue
accrual and strength gains from PRE, compared with physiologic testosterone
replacement alone, in eugonadal men with HIV-associated weight loss.
Protease inhibitors did not prevent lean tissue anabolism.
PMID: 10208143 [PubMed - indexed for MEDLINE]

Am J Manag Care 2000 Sep;6(9):1003-16
Acquired immunodeficiency syndrome wasting, functional performance, and
quality of life.
Roubenoff R.
Jean Mayer United States Department of Agriculture, Human Nutrition
Research Center on Aging, Tufts University, Boston, MA 02111, USA.

Unintentional loss of weight and lean body mass (wasting) is a major cause
of morbidity and mortality in patients with acquired immunodeficiency
syndrome (AIDS). Patients with AIDS wasting (AW) often experience
reductions in lean body mass, muscle strength, and the ability to perform
functions of daily living. Dependence on assistance with activities of
daily living may be associated with a lower quality of life (QOL) and
higher risk of mortality. These factors suggest that slowing or reversing
 the loss of lean body mass in AW can improve well-being. Nutritional
support or appetite stimulants in the absence of exercise therapy or growth
hormone supplementation can increase fat without improving body
composition, whereas appropriate exercise programs, androgen therapy, and
recombinant human growth hormone (rhGH) therapy may increase lean body mass
in patients with AW. Resistance exercise programs can increase muscle
strength and lean body mass. In addition, both resistance and endurance
(aerobic) exercise augment endogenous growth hormone levels, decrease
depression, enhance self-esteem, and may improve immune response.
Randomized, double-blind trials have shown that rhGH therapy increases
total body weight, lean body mass, exercise capacity, and QOL. In summary,
interventions that improve exercise capacity and functional performance may
enhance QOL in patients with AW and may reduce mortality in this group.
PMID: 11184062 [PubMed - indexed for MEDLINE]

Kirsten Myhr
Head of Eastern Region Drug Information Centre

RELIS Ost
Ulleval University Hospital
0407 Oslo, Norway
Tel.: +47 23 01 64 11(o)   Fax: +47 23 01 64 10
+47 22 56 05 85 (h)   mobile: +47 416 38 747
myhr@online.no
www.relis.no




--
Send mail for the `INDICES' conference to `indices@usa.healthnet.org'.
Mail administrative requests to `majordomo@usa.healthnet.org'.
For additional assistance, send mail to:  `owner-indices@usa.healthnet.org'.