Appetite Stimulants, Anabolics, and Beyond
On March 24, 2000, Nutritionists In AIDS Care (NIAC) and the AIDS Wasting Foundation (AWF) presented an all-day conference at Hunter College in New York City. The conference was entitled "Progressive Management of AIDS Wasting: 2000," and one of the speakers, Dr. Lawrence Fontana, spoke on appetite stimulants and anabolic agents used in the management of AIDS wasting. This article is adapted from that presentation.
Wasting and Lean Body Mass
Wasting is defined by the Centers for Disease Control as the involuntary loss of more than 10 percent of baseline body weight. Most dietitians think the defining point should be lower -- 5 percent. Others think it is not simply weight that we should be concerned about, that the loss of body cell mass -- muscle -- is what's really important. Simply put, their position is this: You can think of the body as different compartments -- body cell mass, fat, and water. The body cell mass is the functional tissue and includes the organs -- heart, lungs, liver, pancreas -- and skeletal muscle. We can survive with low body fat, but the organs and skeletal muscles combined are what keep you alive and functional.
Not everyone with HIV or AIDS is on HAART. Some have failed the therapy, while others have not yet started it. In addition, some people on successful HAART just can't seem to gain weight or build muscles. Weight gain in people on protease inhibitors, when it does happen, is mostly fat. Many people on otherwise successful HAART have gained weight, but not in the form of muscles. Instead, they accumulate fat in the abdomen ("protease paunch" or "crix belly") or at the back of the neck ("buffalo hump"). We don't know the long-term consequences of the abdominal fat, but we do know that classic wasting, which includes the loss of body cell mass, is associated with sickness and death.
In the early years of the epidemic, severe wasting was thought to contribute to sickness and death of people with AIDS. Dr. Donald Kotler, a pioneer investigator in the study of body composition and AIDS, began his work at St Luke's/Roosevelt Hospital in New York City. What Dr. Kotler's investigations so clearly reveal is that the compartment called body cell mass -- cells in muscles and organs and circulating cells -- have some very key functions. It's the compartment that uses glucose and oxygen to make energy and facilitates the removal of waste products. It is the compartment that makes heat, synthesizes body proteins, and conducts all the metabolic activity that keeps you alive. Body cell mass is separate from bone, fat, and extracellular water. Body cell mass is protein and intracellular water. What Dr. Kotler's studies showed was that as people got sicker and sicker from AIDS-related infections and cancers, body cell mass was lost and people wasted.
With HAART, including protease inhibitors, and overall better treatment, the immune system gets a boost. There are fewer infections and people are gaining weight. Body composition, however, still remains a critical issue for people living with HIV and AIDS, and body cell mass, the metabolically active compartment, is essential for life.
One of the ways you can determine your body composition is a bioelectrical impedance analysis, or BIA. The BIA is a simple, noninvasive test that takes about five minutes to perform. It involves placing electrodes on the body and taking two readings, reactance and resistance. Along with age, height, weight, and gender, these two numbers are run through computer software. The results indicate percent of body cell mass and body fat, as well as hydration status. For men we hope to see that 40 to 45 percent of weight is body cell mass and 10 to 20 percent is fat. For women, body cell mass should be in the 30 to 35 percent range and fat mass 20 to 30 percent. [Editor's note: For a more complete discussion of bioelectrical impedance analysis, see "Weighing In -- The Modern Way" by Edwin Krales, M.S., C.D./N., in the August 1999 issue of Body Positive.]
Because of the prevalence of wasting among people with HIV and AIDS and similar diseases, pharmaceutical companies have taken the opportunity to develop and market a variety of medications with the potential either to improve appetite or to promote the development of lean body mass (muscle). Here is a brief rundown of what is available, along with some of the pros and cons.
In order to gain weight and put on muscle you have to eat. Over the last couple of years, Body Positive nutrition articles have given you advice about what to eat to maintain a healthy body. But what if you are just not hungry? There are two appetite stimulants commonly used by people with HIV and AIDS: megesterol acetate (Megace) and dronabinol (Marinol).
Megesterol acetate has been the more studied. It was widely used in the treatment of breast cancer when it was discovered that women taking the drug had an increased appetite and gained weight. One of the problems with megesterol acetate is that the weight gain it achieves in people with HIV and AIDS is primarily fat. In men, the fat gain is due in part to the fact that megesterol acetate decreases testosterone production. Other side effects include hormonal problems that include diabetes mellitis. This drug should be avoided if you have deep venous thrombosis (a blood clot, also called DVT). If you decide to take this drug, be sure you consider testosterone measurement and replacement.
Dronabinol is approved for the treatment of anorexia in patients with AIDS. Treatment with this drug stimulates appetite, but, according to most of the studies, weight gain is not significant. There are no studies of dronabinol and body composition, but in the absence of exercise it is likely to be fat. The active compound in dronabinol is a marijuana derivative. In addition to increasing the appetite, dronabinol is also used to relieve nausea and vomiting and as an aid in falling asleep.
Testosterone and other Anabolics
Several anabolic agents have been widely used to treat AIDS wasting. These include testosterone, oxandrolone (Oxandrin), nandralone (Decadurabolin), oxymethalone (Anadrol), and growth hormone (Serostim).
Testosterone is the natural male hormone that differentiates a man from a woman. It is important in the growth of muscle tissue, bone health, sperm production, and both male and female sexual function. It has a breakdown product called estradiol (a female sex hormone), that also helps in bone formation, but which can also cause breast tissue to increase. The other breakdown product of testosterone is dihydroxy testosterone, or DHT. DHT is involved in things we don't like about testosterone, such as facial hair, body hair, acne, loss of scalp hair, and growth of the prostate. Although testosterone levels are higher in youth, young men rarely have enlarged prostates. This problem usually occurs in later years, when more testosterone gets broken down to DHT. Testosterone is primarily a male hormone, but women have some too; their main hormone, however, is estradiol.
Hypogonadism -- low testosterone -- is a common hormonal disorder in AIDS. It is a cause of muscle wasting in AIDS and correlates with disease progression. Hypogonadism can occur as a response to stress, infection, or malnutrition. When women exercise a lot, they often stop menstruating; this is because the excessive exercise causes them to lose some of their testosterone. Marine boot camp is characterized by high stress levels, and the men who are there frequently have testosterone levels as low as those of men who have been castrated. In addition to muscle wasting, low energy, mood changes, and lack of sexual desire are associated with low testosterone levels.
There are two laboratory tests for testosterone. Total and free testosterone are separate entities, and their measurement requires separate lab tests. In most laboratories, a request for testosterone measurement means total testosterone. Total testosterone includes bound testosterone (about 60 percent) that is not available and free testosterone (about 40 percent) that is free-floating and available for anabolic activity. For males, normal levels for total testosterone range from about 300 to 900 ng/dl. Various laboratories have different norms for both total and free. For women, normal levels are 20 to 90 ng/dl for total testosterone.
There are several ways of giving testosterone to hypogonadal men and women. Injection of testosterone cypionate or ethionate every two to four weeks is common practice; the typical men's dose is 200 to 400 mg, and for women it is 25 to 50 mg. Testosterone is also available in a skin patch and a scrotal patch. A new product in the form of a gel is just coming on the market. One of the advantages of the patch or the gel is that serum testosterone levels rise and fall gradually, unlike the rapid -- often disturbing -- spiking from injections.
Medicinal testosterone is not an appetite stimulant. Excess testosterone can be associated with abnormally high numbers of red blood cells, called polycythemia, which can be implicated in heart disease. Other undesirable effects include acne on the back and the face and loss of hair on the head and increased hair on the body. It is important, therefore, to have serum testosterone levels measured and to replace testosterone only if there is a deficiency.
Testosterone is an anabolic-androgenic steroid. "Anabolic" in this sense means muscle-building and red blood cell-producing. The androgenic effects are those of masculinization and producing male sex characteristics. In testosterone, the androgenic and anabolic effects are balanced, so it is ideal for men but has to be given to a woman carefully to avoid the undesirable androgenic effects of facial hair growth and scalp hair loss.
Oxandralone, nandralone, and oxymethalone are testosterone-related agents whose effects are more anabolic and less androgenic. They are designed to increase strength and muscle mass in men and women who already have normal testosterone levels, while avoiding the unwanted androgenic effects of testosterone. This class of drug is referred to simply as anabolic steroids. They create a positive nitrogen (protein) balance; that means instead of nitrogen being lost in the urine it is kept in the muscle.
Oxandralone has very little androgenic activity, which makes it very desirable for women. Because it has such low androgenic activity, in men it almost always has to be given with testosterone. The dose is normally 15 to 20 mg per day. Because it is a relatively weak anabolic steroid, some researchers give much higher doses -- from 40 to 80 mg per day. This is not recommended, however, because of the number of side effects. In one study, people taking oxandralone in conjunction with an exercise and nutrition program gained about 51/2 pounds of muscle.
Oxymethalone is a high-potency anabolic steroid and has more androgenic activity. It is dosed at 50 mg two times per day. For men, this means that muscle growth will be more pronounced and extra testosterone is not likely going to be needed. Oxandralone and oxymethalone are both taken by mouth.
Nandralone deconate is another anabolic steroid, usually given by intramuscular injection twice monthly. Because of its minimal androgenic effects, nandralone deconate is one of the better anabolics for women. It is also a high-potency anabolic steroid and will put on muscle fast. It attaches itself very tightly to the muscle cell, so you need lower doses of it, which in turn means fewer or less severe side effects.
Anabolics can be used effectively by transgenders. For female-to-male transsexuals, the best choice would be the more androgenic agents, such as testosterone or oxymethalone. For male-to-female transsexuals, the best pick is oxandralone or nandralone deconate, both of which are more anabolic than androgenic.
Side Effects of Anabolics
Masculinization effects in women and children require careful monitoring, but are rare with anabolic steroids that have high anabolic-to-androgenic ratios (less testosterone-like effects). Cholesterol is adversely affected. Anabolics activate an enzyme called hepatic triglyceride lipase, which takes HDL (the good cholesterol) out of circulation, thereby lowering the cholesterol/HDL ratio and possibly making it a risk factor for cardiovascular disease. The same enzyme, however, also takes triglycerides, which may promote cardiovascular disease, out of the blood. It is possible that these two effects may counterbalance each other, so the actual risk of heart disease is not really known. Anabolic steroids, like testosterone, stimulate red blood cell production. Because about half of patients with AIDS also have anemia (which also lessens lifespan), this may actually be a beneficial effect of anabolic steroids, treating two HIV-related conditions with one drug.
Liver damage is a concern to anyone taking anabolic steroids, especially in high doses for a long time -- like body builders. There are two mechanisms by which drugs can damage the liver. In the first, there is direct damage of the liver cells. This is what you see in hepatitis, where you get a natural inflammation and rupture of liver cells. These effects are called idiosyncratic, meaning that they are not dose- or time-related and could happen to anyone. They can happen with any drug, but they are not the usual thing. Direct damage is the exception, not the rule, with anabolic steroids.
The way anabolics work is that they interrupt bile flow at the level of the small bile channels (the large ones stay open), so you have increases in bile acids (substances made in the liver that help you digest fat). This can cause increases in liver enzymes and, if allowed to go on, cause your skin and eyes to turn yellow (jaundice). These effects are totally dose- and time-dependent and completely reversible by taking away the drug or reducing the dose. For serious side effects to occur, you usually need high doses for long periods of time, months to sometimes years.
The most worrisome thing we hear about anabolics is cancer. There was a lot of publicity about how Lyle Alzado, a former football player, thought his brain cancer was caused from using anabolic steroids. This is simply not true. There is no association between brain cancers and anabolic steroids. Even liver cancers are very rare in their use. Since their development in the 1950s, fewer than fifty cases have been reported, and half of those patients had a rare anemia, a condition that in itself predisposed them to liver cancer anyway. In all cases, the patients who got cancer, which usually goes away when the anabolic steroids are stopped, were taking high-dose anabolics for two to seven years without a break, something that is never done today. Most doctors cycle anabolic steroids, giving the medication for twelve to 24 weeks at a time, then stopping it for a few months. Given this way there is very little (if any) risk for development of a cancer.
Recombinant growth hormone is an anabolic agent belonging to another class of drugs also used in the treatment of AIDS wasting. Growth hormone is produced naturally in the body; it also directly stimulates an increase in the number of muscle cells. Another effect is that it causes fat to be broken down. Growth hormone must be injected daily, and the side effects include muscle pain and edema of the neck. One of the issues with the use of recombinant growth hormone for lipodystrophy is the cost; at the usual dose of 6 mg, this runs about $150 per day. Investigators are working at lowering the dose while maintaining the effect. Researchers are hopeful that doses between 1 and 3 mg may still be beneficial. Once therapy is discontinued, fat reaccumulates, so the therapy may have to be repeated after a few months. Recombinant growth hormone is not FDA approved for lipodystrophy at this time, but further research might allow it to be approved for this in the future.
If you have lost lean body mass and are able to exercise, that is always the first-line therapy. Whether testosterone, anabolic steroids, or growth hormone is right for you is a decision between you and your physician. Anabolic agents are always more effective when combined with an exercise program that includes resistance exercise, aerobic activity and a healthy diet.
Donna Tinnerello is a dietitian specializing in HIV and nutrition in the community and at Cabrini Medical Center and serves as a consulting dietitian in Dr. Fontana's medical practice. She is past chairperson of NIAC and a co-planner of the conference at which the information contained in this article was presented.
Back to the July 2000 issue of Body Positive Magazine.
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