Q: Can you explain how an anabolic agent such as oxandrolone helps to heal wounds? Are all patients with pressure ulcers and other wounds candidates for this type of therapy?
A: Before deciding on any course of treatment for a patient, the practitioner should understand how the treatment works and the rationale behind it. In the case of anabolic agents, it is important to first understand the body's physiologic stress response to a wound and how supplemental anabolic agents attenuate this response.
The Stress Response
When the body is under stress, either physical or psychological, there is an amplification of the fright-flight reaction. The initial insult leads to local and generalized inflammation and an increase in the level of the stress hormones, particularly catecholamines and cortisol.1 At the same time, levels of anabolic hormones (human growth hormone and testosterone) decrease. This hormonal imbalance leads to a catabolic and hypermetabolic state. A catabolic state is one in which the body breaks down components in order to release energy to meet increased demands. Imagine the body working much harder and faster than usual to fight off the stressor and regain homeostasis. Working harder and faster means an increase in the metabolic rate and an increase in body temperature. To keep up this pace, the body needs an increased supply of glucose, which may come from gluconeogenesis or by rapidly breaking down lean body mass as a means to get more energy.
Loss of Lean Body Mass
If this cycle continues for an extended period of time, a patient will lose weight and more importantly, suffer a loss of lean body mass. Table 1 describes the effects of continued loss of lean body mass. If a patient shows a steady downward trend in body weight, it is unlikely that the body will have a sufficient energy and nutritional substrate from which to build new tissue to heal a wound. In order to build new tissue, protein must be available to fuel an anabolic process. A stressed, catabolic patient will not have this protein available because it will be shuttled off the normal course to be used as energy.
Healing is an anabolic process. Weight loss is a symptom of a catabolic process. Simply put, a patient cannot be anabolic and catabolic at the same time. In other words, healing will most likely take place after the weight loss and catabolic process have been corrected.
Anabolic Agents
One of the newest ways to address the problem of continued involuntary weight loss is with the use of an anabolic agent. Anabolic agents are derivatives of testosterone. They attenuate the catabolic state by decreasing protein breakdown and increasing protein synthesis. Anabolic agents also improve intracellular reutilization of amino acids so that nitrogen is retained in the body rather than excreted. A successful effort has been made to separate the anabolic activity from the androgenic or virilizing activity of testosterone, which means fewer adverse effects. Although several different agents are available, oxandrolone (Oxandrin; BTG Pharmaceuticals, Iselin, NJ) has become a popular choice because of its high level of anabolic activity and safety. Oxandrolone has 6.3 times greater anabolic activity than methyltestosterone.2 Oxandrin is the only oral anabolic agent approved by the Food and Drug Administration to promote weight gain after involuntary weight loss due to surgery, chronic infections, or severe trauma or for any patient who fails to gain or to maintain normal weight. It is also approved to offset the protein catabolism associated with prolonged corticosteroid use.3 Several studies have been conducted using oxandrolone in a variety of patient populations, including patients with burns, cancer, spinal cord injuries, and HIV/AIDS.
Demling and DeSanti4 studied the relationship between restoration of weight loss and healing of the nonhealing wound. The subjects in this study had nonhealing wounds for an average of 12 months, despite good local wound care. All subjects had lost 10% or more of their usual body weight and did not regain the lost weight, despite optimal nutritional intervention. Oxandrolone was added to the treatment regimen for a 12-week period. The authors reported a significant correlation between the subjects' weight restoration and wound healing. The most significant wound healing took place after 50% of the lost weight had been restored.
Conclusions
Wound healing and involuntary weight loss are 2 interrelated clinical problems. To optimize wound healing, the practitioner should examine and document the reasons that a patient continues to lose weight. If weight loss continues despite attempts to maximize nutritional intake and optimize a patient's diet, a hormonal imbalance due to the stress response may be the cause. Anabolic agents such as oxandrolone have been used with success to halt this catabolic process and are worth considering for appropriate patients.
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