Anabolic and Wound Healing Effects of the Testosterone Analog Oxandrolone in the Burn Patient

(Current Evidence)

OXANDROLONE, AN ANABOLIC STEROID, SIGNIFICANTLY INCREASES

THE RATE OF WEIGHT GAIN IN THE RECOVERY PHASE AFTER MAJOR BURNS

Robert H. Demling, M.D. and Leslie DeSanti, RN

We studied the effect of an anabolic steroid, oxandrolone, combined with a high-protein diet (2 g/kg/day) on the rate of weight gain and restoration of muscle function in the recovery phase after deep burns of 30 of 50% of total body surface (n = 7). The findings were compared with findings from an isocaloric (2 g/kg/day protein) diet alone (n = 6). The study was prospective and randomized. Data were also compared retrospectively with data from a group of burn patients treated in the same fashion using a high-calorie, high -protein diet with a protein content of 1.3 to 1.4 g/kg/day (n = 10). Muscle function was quantified using a physical therapy index defining rate of progress (0 = lowest, 10 = highest). Oxandrolone was given in the beginning of the recovery phase in a dosage of 10mg orally twice a day.

The recovery phase was defined as resolution of the hypermetabolic state using physiologic criteria. The study was performed in an acute burn rehabilitation facility where patients were transferred once entering the recovery phase.

Patients in each group were not different with regard to age and burn size. We found that mean weight loss for all patients was 11± 2% of preburn weight during the catabolic phase despite optimum nutrition and early wound closure. Data are presented as mean ± SD. We found that the average weight gain during the first 3 weeks was 14.5± 2.5 pounds and that the physical therapy index was 8.8± 0.5 of recovery in the oxandrolone-protein group (n = 7); both of theses values were significantly greater than the corresponding values in the other groups. In the high-protein alone group (n = 6), weight gain was 7.5± 1.7 pounds and physical therapy index was 7.0± 0.8. In the retrospective group (n = 10), weight gain was 4.4± 0.8 pounds and function index was 4.1± 0.5. The daily caloric intake was not different between groups. Protein content and oxandrolone were the variables. No side effects were noted with oxandrolone.

We can conclude that an anabolic steroid combined with increased protein intake can significantly increase the rate of restoration of weight gain postburn. (J Trauma 1997; 43:47-50) 

THE ANTICATABOLIC AND WOUND HEALING EFFECTS OF THE

TESTOSTERONE ANALOG OXANDROLONE AFTER SEVERE BURN INJURY

Robert H. Demling, MD, Dennis P. Orgill, MD, PhD

The Burn Center, Brigham and Women’s Hospital and Harvard Medical School Boston, MA

Purpose: Severe burn injury leads to marked catabolism and decreased lean mass which can impair healing. Anabolic agents can attenuate net catabolism. Our purpose was to determine whether the testosterone analog, oxandrolone, given during the acute post burn period decreased the degree of nitrogen loss and loss of body weight while also increasing the healing rate of a skin donor site.

Results: Mean burn size was 49± 8% for placebo and 53± 9% of TBS for the oxandrolone group. Smoke inhalation was present in approximately 50% of patients in both groups. All patients survived the burn injury. Net weight loss was 8± 3.1 kg in the placebo group compared with 3± 1.9 kg in the oxandrolone group, a statistically significant decrease. Net daily nitrogen loss over a 3 week period (day 7-28) was 13± 4 g in placebo treated compared to 4± 1.9 g for the oxandrolone group, a statistically significant decrease. The healing time of a standardized donor site, decreased from the placebo group value of 13± 3 days to 9± 2 days for oxandrolone treated patients, a significant improvement. No major liver dysfunction, or other complication attributable to an anabolic steroid was seen in either group.

Conclusion: We found, the anabolic agent, oxandrolone significantly decreased weight loss and net nitrogen loss and increased donor site wound healing compared to placebo controls. We noted no complications with the use of oxandrolone. (J Crit Care, March 2000; 15:12-18)

COMPARISON OF THE ANABOLIC EFFECTS AND COMPLICATIONS OF HUMAN GROWTH

HORMONE AND THE TESTOSTERONE ANALOG, OXANDROLONE, AFTER SEVERE BURN INJURY.

Robert H. Demling, M.D.

The Burn Center, Brigham and Women’s Hospital and Harvard Medical School Boston, MA

Abstract

This study compared the anticatabolic and wound healing effects of the anabolic agents human growth hormone, HGH, and the testosterone analogue, oxandrolone, after severe burn injury. A randomized prospective study design was used. Patients were given HGH at a dose of 0.1 mg/kg/day (n = 20) or oxandrolone, 20mg/day (n = 16), beginning between days 7-10 post-burn. Data was compared to burn patients not placed on either agent (n = 24). Patients were monitored until they were sufficiently healed to be transferred to a rehabilitation center.

The results of our study were as follows: All patients survived. Net weight loss was 82.1 kg in the control group compared with 4± 1.8 kg with HGH and 3± 1.2 kg with oxandrolone, a significant decrease. Net daily nitrogen loss was 12± 3 g in non-treated compared to 3 g of less for each of the anabolic groups, a significant decrease. The metabolic rate in untreated burns was 15525% of predicted normal, compared to 178± 28% for HGH and 156± 20% for oxandrolone treated patients. The complete healing time of a standardized donor site, decreased from the control value of 14± 2 days to 10± 3 days for HGH and 10± 2 days for oxandrolone treated patients, a significant improvement. Hyperglycemia (glucose over 225 mg/dl 12.5 mM) was present in 100% of HGH patients compared to 55% for control and 50% for oxandrolone treated.

We found that both anabolic agents significantly decreased weight and nitrogen loss and increased healing with nearly identical benefits. However HGH resulted in the significant complications of hyperglycemia and accentuated hyper-metabolism. We noted no side effects with oxandrolone. ã 1999 Elsevier Science Ltd and ISBI. (Burns 24; 1999:215-221)

THE EFFECT OF SHORT-TERM OXANDROLONE TREATMENT ON

PERIPHERAL AMINO ACID METABOLISM

Sheffield-Moore M, Ph.D, Ferrando AA, Ph.D., Wolf SE, MD, Herndon DN, MD., Wolfe RR, Ph.D., 

University of Texas Medical Branch/Shriners Burns Hospital, Galveston, Tx.

Burn injury and its associated metabolic derangements often lead to considerable losses in skeletal muscle mass in the burn patient. The ability to reverse these losses in lean body mass in the burn patient, and perhaps increase net protein synthesis, has considerable clinical implications. Oxandrolone (Ox), a synthetic derivative of testosterone, is an oral anabolic steroid indicated for use in patients recovering from severe trauma and burns. In addition, Ox can be used safely in both males and females as it has a low potential for androgenic side effects as compared to other natural androgens. Prior to initiating clinical trials in the burn population, we studied six healthy young males before and after taking an oral dose of Ox (15mg/day) for 5 days. We hypothesized that a short-term administration of Ox would increase net protein synthesis and amino acid uptake. Following an overnight fast, a stable isotope of phenylalanine was infused to determine in vivo net amino acid flux and muscle biopsies were taken from the vastus lateralis to determine muscle fractional synthetic rate (PSR). Net amino acid balance increased from a net efflux as measured before Ox administration to a net uptake into the muscle following short-term Ox administration (-17± 3 vs 0.09± 2%) (p< 0.01). Muscle FSR also increased significantly with Ox from 0.084± 0.02% %/h to 0.1190.03%/h (SEM) (p< 0.05). These data indicate that Ox, given at a moderate dose of 15 mg/day for 5 days, is sufficient to induce increases in net protein synthesis in normal healthy males. The ability of Ox to offset the net catabolism of fasting provides evidence for its use to offset the protein catabolism and muscle wasting of burn injury.

NET AMINO ACID IN FLUX INTO MUSCLE

% of Total

MUSCLE FRACTIONAL SYNTHESIS RATE

PERCENT PER HOUR

EFFECT OF OXANDROLONE ON OUTCOME IN PATIENTS WITH THERMAL INJURY

Aleem RF, MS, RD Walaszek PS, PharmD, Gamelli RL, MD.

Oxandrolone, an anabolic steroid, may enhance patient outcome by reducing protein catabolism, infection rate, length of stay (LOS), and need for inpatient rehabilitation. We retrospectively randomly reviewed 49 charts of burn patients ages 15-75 years of age with > 20% total body surface area (TBSA) burn admitted to our burn center from January 1995 to May 1998. Patients received 90-100% of estimated kcal and protein needs within 24 hours of admission. Group I (n=20) patients received oxandrolone 10mg BID until discharge or wounds < 5% open. Group II (n=29) did not receive oxandrolone. Data analyzed included age, sex, % TBSA burn, % TBSA grafted, presence of inhalation injury, infection rates, albumin/transferrin levels at discharge, number of skin grafting procedures, weight preservation. LOS, and place of discharge. Results: Albumin and transferrin levels were similar in both groups upon discharge. Mortality was 10% in Group I and 7% in Group II, however, Group I patients had a higher rates of % TBSA grafted, and inhalation injury. Oxandrolone administration was associated with decreased LOS, need for inpatient rehabilitation and infection rates

Group I patients had a greater extent of inhalation injury and burn injury requiring grafting, had similar length of stay and weight preservation to Group II patients. The use of oxandrolone appears to be a safe and effective adjunct to optimum nutritional support in patients with thermal injury. (J Burn Care Rehab 2000: 1:197)

THE RATE OF RESTORATION OF BODY WEIGHT AFTER BURN INJURY, USING

THE ANABOLIC AGENT OXANDROLONE, IS NOT AGE DEPENDENT

Robert H. Demling, MD and Leslie DeSanti, RN

Burn Center, Brigham and Women’s Hospital

We determined the effect of age on the restoration of lost body weight and lean mass after burn injury, using the anabolic steroid oxandrolone.

Patients with deep burns of 30 to 55% of body surface were studied when entering the recovery phase of injury, defined as resolution of the hypermetabolic, catabolic state. Patients were provided optimum nutrition and exercise alone or with the addition of oxandrolone. The rate of body weight and lean mass gain and improvement in physical function were measured over a four week period. Four groups were studied. A younger group, mean age of 34 years and burn size of 47± 7% versus an older group, mean age 60 years and burn size 36± 5%. The mean loss of body weight in the younger and older groups was 10± 2 and 11± 2% of total. Both groups were randomly divided into a control and oxandrolone study group.

Weight restoration, 74± 5% of which was lean mass, averaged 1.7± 4 kg and 1.6± 3 kg per week in the young and older oxandrolone groups. This rate was compared with 0.7± 2 kg and 0.5± 2 kg in the young and older control groups, with only 55% of weight gain being lean mass. These differences were statistically significant. The increase in the rate of weight gain with oxandrolone corresponded with a 30% decrease in length of stay in the burn rehabilitation unit.

We concluded that the ability of an anabolic steroid to restore lean mass and physical function after burn surgery is not related to age. (Burns, In press, 2000)

EFFECT OF AGE ON ANABOLIC RESPONSE TO OXANDROLONE AFTER MAJOR BURN

OXANDROLONE, AN ANABOLIC STEROID, ENHANCES 

THE HEALING OF A CUTANEOUS WOUND IN THE RAT

Abstract

We studied the effect of the anabolic steroid oxandrolone, on the healing rate of a standardized full thickness linear wound on the back of the rat. Oxandrolone was given orally by gavage, in peanut oil in a dose of 0.1 mg/kg/day vs. a placebo powder in peanut oil at the same dose.

Parameters monitored were timed to complete closure, wound hydroxyproline content and tensile strength as well as histology. We found that wounds completely closed in 12± 3 days with oxandrolone compared to 18± 3 days for a placebo, a significant difference. The rate of body weight gain was identical in both groups. Hydroxyproline content of the healed incision site was 23± 4 mg/gm tissue versus 17± 3 mg/gm tissue, in the oxandrolone versus placebo group. Tensile strength was 185± 13 gm/mm² vs 102± 18 gm/mm² with oxandrolone versus placebo. Both parameters were significantly increased with the anabolic steroid. Histology demonstrated a more mature collagen dense hypercellular wound with oxandrolone.

We conclude that the anabolic steroid oxandrolone significantly enhanced wound heali8ng unrelated to any generalized increase in protein mass as would be reflected in body weight. (Wound Regeneration and Repair, March/April 2000)

Figure 2. A typical sample of a wound in the oxandrolone fed group is shown in a lower power photomicrograph. The healing dermal collagen is more dense and the wound more cellular than other groups. The wound histology reflects a more mature healing wound than the other groups