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Motivation to comply with treatment is high
Researchers at Columbia University report a significant improvement in mood, energy levels, libido, and muscle mass in HIV-positive men after they have been treated with testosterone therapy.
"People say they have more energy to face the day and that they’re more alert and interested and becoming engaged in daily activities," says Judith G. Rabkin, PhD, MPH, professor of clinical psychology in psychiatry in the College of Physicians and Surgeons at Columbia University in New York City.
The therapy, which consisted of an eight-week trial for all participants and an additional four weeks for responders, also significantly improved muscle mass, especially if the men exercised, Rabkin says.
Rabkin is one of three researchers who have submitted a report on their findings, titled "Testosterone therapy for HIV+ men with and without hypogonadism," to the Journal of Clinical Psychopharmacology for publication this winter. The researchers also have written a paper on the "Effects of testosterone therapy on weight and body composition in men with HIV-related weight loss," which is expected to be published this year in Nutrition Research.
The study, conducted from 1993 to 1995, consisted of 112 men who completed at least eight weeks of treatment with 400 mg intramuscular testosterone cypionate biweekly. Responders continued to take testosterone for another four weeks, and then they were randomized in a double-blind placebo-controlled six-week discontinuation trial.
"The first thing the men noticed was a loss of energy when they were put on a placebo," Rabkin says.
No women were studied because testosterone is not indicated for use by women. The men, age 18 or older, had CD4 cell counts below 400 cells/mm3, and they had clinically deficient or low-normal serum testosterone levels of less than 500 mg/dl, with or without problems in erectile or orgasmic function.
They also reported a significant diminution of sexual desire and at least one additional symptom of low mood, low energy, or weight loss. They were screened by telephone and were evaluated with a psychiatric assessment, as well as social, sexual, medical, and family histories. They were given follow-up assessments and had blood drawn.
The study excluded men who had any of the following problems within the previous six months: substance use disorder; psychotic symptoms; significant suicidal risk; unstable medical condition including new onset or new episode of an opportunistic infection in the past month; or recent use of androgenic-anabolic steroids.
Researchers gave the men injectable testosterone because it’s inexpensive and effective. "There are testosterone patches, and some people prefer these if they don’t want injections," Rabkin says.
"We did one study with patches that spare people the bother of getting an injection every two weeks," Rabkin adds. "But the patches deliver a considerably lower dose and they are eight times as expensive, so for some people the dose is not enough."
The study took place before protease inhibitor therapy was available, and the men studied were very sick, with the majority having a life expectancy of less than one year, Rabkin says.
In a subsequent testosterone study conducted in 1998 to confirm the earlier results, the men were healthier and some even returned to work.
Rabkin often is asked about the ethical concerns surrounding administration of testosterone to men whom society may not want to be sexually active because of the nature of their sexually transmittable disease. She replies that the study included only men who had engaged only in safe sex during the last three months of sexual activity.
"We also asked them questions about risk behavior and offered them counseling if they wanted it," Rabkin says.
For some of the men, their quality of life improved even if their only sexual activity was masturbation. For others, the improvement in libido could have made safe sex more likely, Rabkin says. "When men are having trouble with arousal, it’s harder to put on a condom because of a weak erection."
The study showed that testosterone treatment increased the HIV-positive men’s feelings of overall well-being.
The study reported a variety of other positive effects, as well. They are:
• Mood. The study assessed mood at baseline with a Structured Clinical Interview for DSM III-R, which stands for Diagnostic and Statistical Manual of Mental Disorders — Third Edition Revised.1 Also, the study doctor administered the 21-item Hamilton Depression Rating Scale (HAM-D) at baseline and biweekly. Of 41 patients with major depressive or dysthymic disorders, 34 completed at least eight weeks of open treatment. Both clinician-rated and self-rated measures of depressive symptoms showed significant improvement over eight weeks. The HAM-D scale showed significant improvement as well.
• Muscle mass. The muscle mass of HIV- positive men is important to watch because an HIV-positive person’s muscle mass may be depleted even if the body weight remains unchanged or increases.2 The report’s findings involved 52 men, each of whom had less than 90% of their normative body cell mass. Of the 52, 44 (85%) completed 12 weeks of testosterone treatment. After the 12 weeks of treatment, the average weight gain was 2.4 kg, with a range from a loss of 5 kg to an increase of 9.5 kg. All measures of body composition, except for total body water, increased significantly from the baseline to the 12th week, including body-cell mass and fat-free mass. The men also reported stronger appetites.
"It helps if they exercise," Rabkin says. "In the beginning, they may not have the energy to exercise, but those who did gained more weight."
• Energy. The study showed that at baseline, 87 men (79%) reported low energy and fatigue. After testosterone treatment, 61 (70%) had clear-cut improvement, according to what the men reported and physician assessment based on CGI ratings and a 10-point visual analog scale.
Overall, the study’s findings backed up the men’s self-reports of how much better they felt with the testosterone treatment.
There are side effects to using testosterone; the most common one in this study was irritability. The men gave examples of having an increased likelihood of complaining if pushed in the subway or if someone cut in front of them in the grocery store line. The study concludes that this type of behavior is often within the range of normal behavior.
"The most annoying side effects for the men we treated have been acne and hair loss, and some people just don’t want to continue with the treatment," Rabkin says.
Hair loss was reported by 6% and acne by 7% of the men. Of 124 patients, 49 (40%) reported at least one side effect at one of the four times during the first eight weeks of treatment. But none of the side effects were persistent except for acne and hair loss.
"All the side effects are reversible if you lower or stop the dose," Rabkin adds.
Rabkin suggests that clinicians who consider testosterone therapy for HIV-positive men should consider these guidelines:
• Test the patient’s serum testosterone levels at regular intervals to make sure the treatment is working. "If patients say they are not getting much of an effect and the serum levels are low, that would be an indication to raise the dose," Rabkin says.
• Monitor the serum testosterone levels to make sure the dose doesn’t bring the levels up to more than double the top of the normal range. "If it was more than double the top number, we reduced the dose," Rabkin says. "We also used larger doses than endocrinologists use because we didn’t get any effect with lower doses."
• Watch for irritability that falls outside of normal behavior.
• Don’t give testosterone treatment to men with bipolar illness because of the possibility of the men developing an irritable mania.
• Consider having the patient take testosterone therapy for as long as needed. "It’s worth stopping it to see if the patient doesn’t notice a difference, because then the patient doesn’t have to keep getting injections," Rabkin says.
• Some patients can learn to self-inject testosterone.
• Older men should be screened for prostate cancer, because the one medically serious side effect of testosterone is possible exacerbation of prostate cancer.
• For patients who are clinically depressed, the clinician might want to go the conventional route and try giving the patient Prozac first, and then use testosterone adjunctively if there are still residual problems with energy, libido, and weight loss, Rabkin says.
1. Spitzer RL, Williams JBW, Gibbon M. First MB. Structured Interview for DSM-IIIR (SCID). Washington, DC: American Psychiatric Association Press; 1990.
2. Kotler DP, Tierney AR, Wang J, Pierson RN. Magnitude of body cell mass depletion and timing of death from wasting in AIDS. Am J Clin Nutr 1989; 50:444-447.