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From the Clinical Research Centers |
Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science (S.B., T.W.S., I.S.-H. R.S.), Los Angeles, California 90059; the Laboratory of Exercise Science, El Camino College (T.W.S.), Torrance, California 90504; Harbor-University of California-Los Angeles Medical Center (G.B.), Torrance, California 90502; SmithKline Beecham Pharmaceutical Co., Collegeville, PA 19426 (N.A.-S.); Center for Health Sciences, University of California School of Medicine (A.K., R.H.), Los Angeles, California 90024; and Karolinska Institute (S.A.), Stockholm, Sweden
Address all correspondence and requests for reprints to: Shalender Bhasin, M.D., Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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We randomly assigned 41 HIV-infected, ambulatory men, 18–60 yr of age, with serum testosterone levels below 400 ng/dL, to 1 of 2 treatment groups: group I, two placebo patches (n = 21); or group II, two testosterone patches designed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment.
Serum total and free testosterone and dihydrotestosterone levels increased, and LH and FSH levels decreased in the testosterone-treated, but not in the placebo-treated, men. Lean body mass and fat-free mass, measured by dual energy x-ray absorptiometry, increased significantly in men receiving testosterone patches [change in lean body mass, +1.345 ± 0.533 kg (P = 0.02 compared to no change); change in fat-free mass, +1.364 ± 0.525 kg (P = 0.02 compared to no change)], but did not change in the placebo group [change in lean body mass, 0.189 ± 0.470 kg (P = NS compared to no change); change in fat-free mass, 0.186 ± 0.470 kg (P = NS compared to no change)]. However, there was no significant difference between the 2 treatment groups in the change in lean body mass. The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels (r = 0.41; P = 0.02). The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches (P = 0.04). There was no significant change in body weight in either treatment group. Changes in overall quality of life scores did not correlate with testosterone treatment; however, in the subcategory of role limitation due to emotional problems, the men in the testosterone group improved an average of 43 points of a 0–100 possible score, whereas those in the placebo group did not change. Red cell count increased in the testosterone group (change in red cell count, +0.1 ± 0.1 1012/L) but decreased in the placebo group (change in red cell count, -0.2 ± 0.1 1012/L). CD4+ and CD8+ T cell counts and plasma HIV copy number did not significantly change during treatment. Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group.
Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass, a significantly greater reduction in fat mass than that achieved with placebo treatment, an increased red cell count, and an improvement in role limitation due to emotional problems. Further studies are needed to assess whether testosterone supplementation can produce clinically meaningful changes in muscle function and disease outcome in HIV-infected men.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Of the various anabolic interventions being considered for promoting restitution of body cell mass in HIV-infected men, testosterone is particularly attractive because it is safe and relatively inexpensive (22). Several formulations for androgen delivery, including injectable esters and transdermal systems, are available for clinical use (22). Studies using either testosterone replacement or supraphysiological doses of testosterone have demonstrated no significant systemic toxicity with testosterone esters or transdermal testosterone formulations (22, 23, 24, 25, 26). Furthermore, replacement doses of testosterone increase fat-free mass, muscle size, and strength in healthy, hypogonadal men and castrated male animals (27, 28, 29, 30, 31, 32, 33). Modest gains in lean body mass and grip strength have been reported after testosterone replacement in older men with serum testosterone levels less than 400 ng/dL (34, 35, 36). We hypothesized that testosterone replacement would have anabolic effects in HIV-infected men with testosterone levels less than 400 ng/dL similar to those observed in older men with low testosterone levels and in healthy, hypogonadal men.
This study assessed whether replacement doses of testosterone, administered by means of Androderm, a nonscrotal transdermal system, augment lean body mass, body weight, muscle strength, health-related quality of life, and Karnofsky performance scores in HIV-infected men with low testosterone levels. By recruiting stable, ambulatory, HIV-infected men with low testosterone levels, we aimed to select patients with intermediate disease severity who had the best chance of demonstrating benefits from testosterone replacement therapy.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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This was a single center, double blind, placebo-controlled, randomized study in which the 12-week treatment phase was preceded by a 2-week screening period. Patients fulfilling the inclusion criteria were randomly assigned to one of two treatment groups: group I, two placebo patches applied every 24 h; and group II, two active testosterone transdermal system patches applied every 24 h (approximate testosterone delivery of 2.5 mg/patch over 24 h).
The protocol and statement of informed consent were approved by the institutional review board of Harbor-University of California-Los Angeles Research and Education Institute. Written informed consent was obtained from each patient before entry into the study.
Patients
The participants were HIV-infected men, 18–60 yr of age, who were ambulatory and had serum testosterone levels below 400 ng/dL. We excluded patients with acute opportunistic infections, malignant disease that required active treatment, fever, long standing hypogonadism from a known cause, or unremitting diarrhea. Patients with evidence of clinically significant cardiovascular, liver, prostatic disease, uncontrolled hypertension, diabetes, respiratory disease, or recent history (last 6 months) of illicit drug use or heavy drinking were also excluded. Additional exclusion criteria included aspartate aminotransferase or alanine aminotransferase greater than 3 times the upper limit of normal, serum bilirubin greater than 2 mg/dL, and prostate-specific antigen (PSA) greater than 4 ng/mL.
Drug administration
Two testosterone or two placebo patches were applied to the skin of the abdomen, back, arms, or thighs nightly for 12 weeks. At the end of each 2-week period, patients returned all unused patches so that a count of returned patches could be made.
All concomitant medications taken during the study were recorded. Patients who received antiretroviral therapy or drugs for treatment or prophylaxis of disorders associated with HIV infection continued to receive those medications during the course of the study. The patients were excluded from the study if they had received ketoconazole, megestrol acetate, anabolic/androgenic steroids, androgen antagonists, finasteride, GH, or insulin-like growth factor within 3 months of study entry.
Outcome measures
The primary efficacy variable was change in lean body mass at the end of the 12-week treatment period, measured by dual energy x-ray absorptiometry (DEXA). Lean body mass was calculated by subtracting bone mass from fat-free mass. The secondary efficacy variables were change in body weight, muscle strength, Karnofsky performance status, and Health Related Quality of Life (HRQOL). Serum total and free testosterone, dihydrotestosterone, LH, FSH, and sex hormone-binding globulin (SHBG) levels were measured on several occasions during the control and treatment periods. Absolute and percent CD4+ and CD8+ T lymphocyte counts, and plasma HIV copy number measured by RT-PCR were measured twice during the control period and during treatment weeks 10 and 12. The patients underwent evaluation for adverse experiences every 2 weeks.
Statistical analyses
Because a change in lean body mass was our primary outcome variable, we did not analyze subjects who did not have posttreatment DEXA scanning. The secondary variables were analyzed on an "as available" basis. All men who dropped out did so before week 10 and did not have a posttreatment DEXA scan. There was only one protocol violator, and he did not have efficacy measurements while receiving treatment. The analysis, therefore, was performed on all randomized patients for whom efficacy data were available. For secondary variables, the last values carried forward for withdrawn patients were analyzed.
Continuous data are reported as the mean ± SE, and categorical data are reported as frequency tabulations. All variables were examined to determine their distribution characteristics. Variables that did not meet the assumption of a normal distribution were log transformed and retested. If the assumption of normality could not be met by transformation, then nonparametric methods were used for analysis. The following variables were analyzed using log transformation: fat mass and muscle strength in the squat and bench press exercises. The Karnofsky scores did not meet the assumptions necessary for t tests and were analyzed using Wilcoxon’s rank sum test.
t tests for independent groups were used to compare a change from baseline between the two treatment groups for DEXA measures, muscle strength, and hormone levels. Additionally, DEXA measures and muscle strength were analyzed using paired t test to detect a nonzero change from baseline at week 12 within each treatment group. Between-group comparisons of Karnofsky scores were made using Wilcoxon’s rank sum test for the reasons stated above.
Methods
Body composition was assessed by DEXA scan (Hologic 4500, Hologic Corporation, Waltham, MA). Serum total testosterone levels were measured in a direct immunoassay using iodinated testosterone as tracer (37, 38). Free testosterone levels were measured by equilibrium dialysis (38). The sensitivities of the total testosterone and free assays were 0.44 ng/dL, and 0.6 pg/mL, respectively. Intra- and interassay coefficients of variation for the total testosterone assays were ±8.2% and ±13.2%, and those for free testosterone were ±4.2%, and ±12.3%, respectively. Dihydrotestosterone was extracted from serum samples by hexane and ethyl acetate and was separated by Celite chromatography before RIA. The sensitivity of the dihydrotestosterone assay was 2.5 ng/dL, and intra- and interassay coefficients of variation were ±9.3% and ±12.7%, respectively. Serum LH and FSH levels were measured by sensitive and specific, two-site-directed, immunofluorometric assays (37). The sensitivities of the LH and FSH assays were 0.05 and 0.15 U/L, respectively. The intra- and interassay coefficients of variation for LH were ±10.7% and ±13.0%, and those for FSH were ±3.2% and ±11.3%, respectively. Serum SHBG levels were measured by an immunofluorometric assay (37). The sensitivity of the SHBG assay was 6.25 nmol/L, and the intra- and interassay coefficients of variation were ±10% and ±10.2%, respectively. Plasma HIV ribonucleic acid (RNA) copy number was measured by RT-PCR.
Measurement of muscle strength
Muscle strength was measured by the one repetition maximum method, using Olympic bars and free weights for the parallel squat and bench press exercises. The exercises were selected to represent measures of upper and lower, and upper body muscle strength, respectively. All subjects underwent an instructional period in which lifting mechanics and safety were explained and demonstrated. The subjects practiced with light resistance until investigators confirmed proper technique. After a 5-min rest period, the subjects began by performing one set of 5–10 repetitions of the selected exercise using 40–60% of an estimated maximum. The resistance was progressively increased until the subjects could not complete the lift; the last successfully completed lift was recorded as the one repetition maximum.
HRQL
The HRQL survey was based on previously developed measures (39, 40). It included multiitem measures of physical functioning [10 items;
internal consistency reliability index (
) = 0.91 on a scale of
0–1], role limitation due to physical problems (4 items; = 0.90),
general health perceptions (5 items; = 0.86), emotional well-being
(5 items; = 0.77), role limitation due to emotional problems (3
items; = 0.94), social functioning (2 items; = 0.52), energy (4
items; = 0.77), cognitive function (3 items; = 0.77), and
sexual function (6 items; = 0.90). Also included in the survey was
a 22-item symptom checklist (extent to which symptoms interfered with
normal activity during the past 4 weeks), a disability days item, an
overall health rating item, and a self-reported time tradeoff
preference assessment. Bivariate associations between treatment group
(placebo = 0; testosterone = 1) and the HRQOL measures
were estimated using product-moment (point-biserial)
correlations.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Forty-one HIV-infected men who met the eligibility criteria were randomly assigned to either the placebo or testosterone group. Of the 21 men randomized to the placebo group, 18 completed the study; of the 20 subjects assigned to the testosterone group, 14 completed the study. One participant in the testosterone group withdrew because of adverse experience (suicidal drug overdose). Three men in the placebo group and 5 in the testosterone group were lost to follow-up or discontinued treatment due to nonstudy-related personal reasons or failure to comply with the protocol. Three men withdrew in the first 15 days of the treatment period; 6 additional men withdrew before completing 10 weeks of treatment.
Baseline characteristics of the patient population
The two groups were similar with respect to age, race, baseline
weight and height, CD4 and CD8 lymphocyte counts, plasma HIV RNA copy
number, Karnofsky performance score, and serum testosterone levels
(Table 1
). Consistent with the prevalent
clinical practice, most patients in both treatment groups were
receiving antiretroviral therapy. Mean serum testosterone levels were
211 and 258 ng/dL in the placebo and testosterone treatment groups,
respectively. The participants were ambulatory and had high Karnofsky
performance scores (Table 1).
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All participants who completed the study used more than 75% of the dispensed patches; 88% used more than 90% of dispensed patches.
Efficacy variables
Lean body mass did not change in the placebo group (50.072 ±
1.514 vs. 50.700 ± 1.669 kg, pretreatment
vs. posttreatment lean body mass, measured by DEXA; change,
0.189 ± 0.470 kg; P = NS), but increased
significantly in the testosterone-treated men [51.264 ± 1.694
vs. 53.408 ± 1.992 kg; change, 1.345 ± 0.533 kg;
P (compared to zero change) = 0.0254; Fig. 1A]. The change in lean body mass was
not significantly different between the two treatment groups. The
change in lean body mass correlated with the change in testosterone
levels during treatment (r = 0.41; P = 0.02; Fig. 2); in general, men who had greater
increments in testosterone levels during treatment experienced greater
gains in lean body mass.
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). The change in fat-free mass was not
significantly different between the two treatment groups.
Fat mass, estimated as the difference between total body weight and
fat-free mass, decreased in the testosterone-treated men (change in fat
mass, -0.569 ± 0.573 kg), but increased in the placebo-treated
men (+0.880 ± 0.520 kg); the reduction in fat mass in the
testosterone group was significantly greater in the testosterone group
than in the placebo group (P = 0.04, Fig. 1C). Total
body weight did not change in either treatment group (change in weight,
0.6 ± 0.7 and 0.6 ± 0.5 kg in the placebo and testosterone
groups, respectively; Fig. 1D).
The change in strength in either the squat or the bench press exercise was not significantly different between the two treatment groups. There was a significant increase in muscle strength in both treatment groups in the squat [change in squat strength in the placebo and testosterone groups, respectively, 4.5 ± 2.0 (P = 0.0011 compared to zero change) and 4.5 ± 1.6 (P = 0.0001 compared to zero change) kg] and the bench press exercises [change in bench press strength in the placebo and testosterone groups, respectively, 1.4 ± 1.2 (P = 0.0001 compared to zero change) and 1.1 ± 2.0 (P = 0.001 compared to zero change) kg]. Karnofsky performance scores did not significantly change in either treatment group and were not significantly different between the two treatment groups.
Hormone levels
Androderm treatment increased serum total testosterone levels in
HIV-infected men from a baseline of 258 ± 50 ng/dL to an average
of 367 ± 35 ng/dL during the treatment period (Table 2A).
The comparison of change in total testosterone levels from baseline
between the two groups was statistically significant (P
= 0.0449). Serum free testosterone levels also increased in men
receiving testosterone patches (Table 2A). The ratio of free to total
testosterone levels did not change in either treatment group (data not
shown). Serum dihydrotestosterone levels increased in men receiving
testosterone patches, but not in those receiving placebo patches (Table 2A); however, the ratio of serum testosterone to dihydrotestosterone
levels did not change in either treatment group (data not shown). There
was also a statistically significant decrease in serum LH
(P = 0.001) and FSH (P = 0.0146) levels
in testosterone-treated men (Table 2B). Serum SHBG levels did not
change in either group.
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Changes in HRQOL scores between week 6 and baseline were not significantly correlated with treatment group (Tables 3A and 3B). The largest correlation was for change in role limitations due to emotional problems (r = 0.33; P = 0.0571). Those in the treatment group tended to improve more on this role functioning measure, but the difference in change between the treatment and control groups was not statistically significant. Change between week 12 follow-up and baseline HRQOL scores did not correlate significantly with treatment group, except for the role limitations due to emotional problems scale (r = 0.43; P = 0.0136). The men in the treatment group improved an average of 42.86 ± 11.8 (mean ± SEM) points on the 0–100 possible score, whereas those in the placebo group did not change (mean ± SEM, 0.00 ± 11.11).
Adverse experiences
Nine men in the placebo group and 11 in the testosterone group reported adverse experiences. There was no significant difference in the frequency of adverse experiences between the 2 treatment groups. Among the men receiving placebo, 3 experienced skin reactions at the patch application site; other adverse experiences were related to resistance mechanism (3 men), gastrointestinal tract (1 man), and urinary system (1 man). In the testosterone group, 5 men experienced reactions at the application site; other adverse experiences in this group included problems related to resistance mechanism (2 men), gastrointestinal system (2 men), and skin and appendages (1 man). All but 1 of the adverse experiences were of mild or moderate intensity. One severe adverse experience (a suicidal amitriptyline overdose) was recorded in the testosterone group. Overall, 19% of participants experienced skin reactions at the site of the placebo or testosterone patch application. The mean primary skin irritation score on the Modified Marzulli and Maibach scale was less than 0.1 on most treatment days, indicating that the skin reactions were usually mild. One man experienced blister formation on 1 occasion; this was related to rupture of the patch in this patient.
The mean red cell counts increased in the testosterone group (change in red cell count, +0.1 ± 0.1 1012/L) and decreased in the placebo group (change in red cell count, -0.2 ± 0.1 1012/L). Hemoglobin levels increased in the testosterone group (change from baseline, +2.9 ± 2.9 g/L), but decreased in the placebo-treated men (change from baseline, -4.5 ± 4.8 g/L). Absolute and percent CD4+ (change from baseline, -26 ± 17 vs. -28 ± 13 cells/cm, placebo vs. testosterone groups) and CD8+ (change from baseline, 13 ± 47 vs. -69 ± 52 cells/cm, placebo vs. testosterone group) T cell counts and plasma HIV RNA copy number (change from baseline, -3.9 ± 3.7 x 105 vs. -1.6 ± 0.9 x 105 copies/mL; P = NS, placebo vs. testosterone group) did not change significantly in either treatment group. Mean serum PSA levels did not change significantly in either treatment group and were not significantly different between the two groups (change from baseline, -0.01 ± 0.24 vs. +0.05 ± 0.04 ng/mL; P = NS, placebo vs. testosterone group). None of the participants had a clinically significant increase in serum PSA levels, defined as a sustained increase to a level over 4 ng/mL. There were no significant changes in total cholesterol, high density lipoprotein cholesterol, or low density lipoprotein cholesterol levels in either group. Three men in the placebo and three in the testosterone group had significant increases in alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, and/or alkaline phosphatase levels.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The magnitude of increase in lean body mass (1.35 kg) was similar to or better than that reported with other anabolic agents approved for the treatment of HIV wasting. The HIV-infected men treated with Megace experienced a 2-lb weight gain on the average (41, 42); however, Megace treatment did not augment lean body mass. This progestational agent lowers serum testosterone levels (41, 42), impairs sexual function, and can produce other consequences of androgen deficiency, including osteopenia and further depletion of lean body mass.
Treatment of HIV-infected men with human GH (hGH) was associated with a 1.5-kg increase in lean body mass in a recent study (43). Although greater gains in weight were recorded after 6 weeks of hGH treatment, these gains were not sustained with continued treatment for 12 weeks. It is conceivable that weight gain early in the course of treatment is due to water retention. GH administration is associated with a high frequency of side-effects, including edema, arthralgias, myalgias, and jaw pain (43, 44). Not surprisingly, the treatment discontinuation rates were high (21–40%) in the two hGH studies (43, 44). The annual cost of treating HIV-infected men with hGH is substantially greater than that of testosterone replacement therapy using any of the available androgen formulations [source: PriceProbe (1997), First Data Bank/Hearst Corp., San Bruno, CA].
Controlled and blinded studies with other androgens have demonstrated gains of similar or lesser magnitude in lean body mass. Some open label, uncontrolled studies (45, 46, 47, 48, 49) with androgens have reported greater gains in body weight and lean body mass; however, those data are not interpretable because of problems of study design. Hengge et al. (49) administered oxymethalone alone or in combination with ketotifen (an H-1 receptor antagonist). Compared to a separate group of 30 untreated matched controls, the HIV-infected men receiving oxymethalone or combined therapy experienced greater weight gain. However, the study was neither placebo controlled nor randomized, and body composition was not examined. In another uncontrolled, open label study, Rabkin et al. (48) reported improvement in morning and daytime erections, sexual desire, energy and appetite, and weight gain in HIV-infected men receiving 400 mg testosterone enanthate every 2 weeks. Poles et al. (50) reported a 1.9-kg gain in body cell mass in HIV-infected men with weight loss of greater than 5% of the usual body weight who received 10 mg oxandrolone, twice daily for 120 days. This was an open label, uncontrolled study in which body cell mass was measured by bioelectrical impedance. Berger et al. (46) reported significant weight gain in men with AIDS-related myopathy; data on body composition and muscle strength were not reported. In a 16-week, placebo-controlled study (50) the men receiving 100 mg nandrolone decanoate weekly experienced a mean weight gain of 3.0 lb.
A multicenter, placebo-controlled, randomized clinical trial using the
scrotal patch, Testoderm, did not demonstrate significant changes in
body weight or composition in testosterone-treated HIV-infected men
(Dobs, A., personal communication; Testoderm press release). The
Testoderm study differed from our study in two important aspects.
First, the participants in the Testoderm study had higher baseline
testosterone levels (mean pretreatment testosterone level of 
400
ng/dL) than those enrolled in our study (mean pretreatment testosterone
level of 250 ng/dL). Second, the patients in the Testoderm study had
more advanced disease than the subjects in our study; the entry
criteria included weight loss of 10% or more in the preceding 6
months.
There was a significant increase in muscle strength in both the placebo-treated and testosterone-treated men, but the changes in strength in either the squat or the bench press exercise were not significantly different between the two groups. The strength gains could be due to improved nutrition in both groups because of counseling and increased contact with medical personnel. More likely, this represents a training effect (ability to lift a greater amount of weight because of increased familiarity with the technique). The men in this study were untrained individuals and therefore more susceptible to training effect than trained athletes. In previous studies with testosterone, we recruited men with weight-lifting experience to minimize changes in strength due to training effect; this was not possible in these patients.
We do not know whether a mean 1.345-kg gain in lean body mass is clinically significant. The AIDS Clinical Trials Group Wasting Task Force has concluded that a 1.5-kg increase in lean body mass is meaningful, especially if it is associated with improvements in other outcomes (Dr. Fred Sattler, Chair, AIDS Wasting Task Force, personal communication). Studies of testosterone replacement in older men with testosterone levels less than 400 ng/dL have reported either gains of 1–2 kg or no change in fat-free mass (34, 35, 36). The changes in body composition associated with testosterone treatment in HIV-infected men were comparable or better and were associated with improvements in hemoglobin and role limitation due to emotional problems.
Testosterone treatment was safe and well tolerated. The only adverse experiences considered related or possibly related to treatment were skin reactions at the application site in 19% of treated men. We did not detect any significant abnormalities in the prostate on digital rectal examination or determination of serum PSA levels. Plasma lipid levels did not change in either treatment group. Testosterone did not significantly affect plasma HIV RNA copy number or CD4+ and CD8+ cell counts.
The red cell count and hemoglobin level increased moderately with testosterone treatment. In HIV-infected men, increased red cell mass is a beneficial consequence of testosterone treatment.
Serum total and free testosterone and dihydrotestosterone levels increased significantly in men receiving testosterone patches, but not in those receiving placebo patches. Androderm treatment suppressed serum LH and FSH levels, providing evidence of an androgenic effect on the pituitary. Taking into account a pretreatment testosterone level of approximately 250 ng/dL and the partial suppression of endogenous testosterone production by exogenous androgen delivered by the patch, we expected serum testosterone levels to rise to 500 ng/dL in the Androderm group (26). It is not clear why the observed testosterone levels in HIV-infected men receiving the patch were lower. Lower testosterone levels in our patients suggest that either a smaller amount of testosterone was delivered across the skin by the patch or the metabolic clearance was higher in HIV-infected men than in healthy, hypogonadal men. Previous data on the pharmacokinetics of testosterone release from the nongenital patch were obtained in a predominantly Caucasian, hypogonadal population. In contrast, a third of our participants were African-American, and another third were Hispanic. We do not know whether there are ethnic differences in the transdermal delivery of testosterone. Although patients were advised to apply the patches nightly, some patients found it more convenient to apply the patches in the morning; therefore, the morning testosterone levels may have represented nadir levels in these men.
We conclude that Androderm treatment of HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass, a significantly greater reduction in fat mass than that achieved with placebo treatment alone, increased red cell count, and an improvement in role limitation due to emotional problems. Favorable changes in body composition, substantially lower cost relative to other anabolic agents such as Megace and hGH, and a lower frequency of side-effects compared to Megace and GH provide the rationale for further evaluation of this anabolic agent. Further studies are needed to determine whether physiological testosterone replacement can produce clinically meaningful changes in muscle function and disease outcomes in HIV-infected men.
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Footnotes |
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Received March 19, 1998.
Revised May 8, 1998.
Accepted May 21, 1998.
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T. W. Storer, L. Magliano, L. Woodhouse, M. L. Lee, C. Dzekov, J. Dzekov, R. Casaburi, and S. Bhasin Testosterone Dose-Dependently Increases Maximal Voluntary Strength and Leg Power, but Does Not Affect Fatigability or Specific Tension J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1478 - 1485. [Abstract] [Full Text] [PDF]
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I. Sinha-Hikim, J. Artaza, L. Woodhouse, N. Gonzalez-Cadavid, A. B. Singh, M. I. Lee, T. W. Storer, R. Casaburi, R. Shen, and S. Bhasin Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E154 - E164. [Abstract] [Full Text] [PDF]
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S. Basaria, J. T. Wahlstrom, and A. S. Dobs Anabolic-Androgenic Steroid Therapy in the Treatment of Chronic Diseases J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5108 - 5117. [Abstract] [Full Text] [PDF]
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 N. Dejucq and B. Jegou Viruses in the Mammalian Male Genital Tract and Their Effects on the Reproductive System Microbiol. Mol. Biol. Rev., June 1, 2001; 65(2): 208 - 231. [Abstract] [Full Text] [PDF]
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A. S. Dobs, P. S. Bachorik, S. Arver, A. W. Meikle, S. W. Sanders, K. E. Caramelli, and N. A. Mazer Interrelationships among Lipoprotein Levels, Sex Hormones, Anthropometric Parameters, and Age in Hypogonadal Men Treated for 1 Year with a Permeation-Enhanced Testosterone Transdermal System J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1026 - 1033. [Abstract] [Full Text]
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