Testosterone supplementation did not show consistent benefit for cardiovascular risk , sexual function , mood and behavior , or cognition .
Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo .
Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido .
Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function .
Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality , psychological well-being , or mood .
Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of " low testosterone " ( low-T ) for cardiovascular health , sexual function , muscle weakness or wasting , mood and behavior , and cognition .
Effects of Androgen Administration in Men with the AIDS Wasting Syndrome
The AIDS wasting syndrome is characterized by loss of lean body mass out of proportion to weight [ 1 , 2 ] . The few effective treatments that have been identified are short-term pharmacologic agonists . Because loss of lean body mass is associated with decreased survival in men with the AIDS wasting syndrome [ 3 ] , development of therapeutic strategies to increase lean body mass is of critical importance . Half of all men with AIDS are hypogonadal [ 4 ] , and serum and rogen levels correlate with lean body mass among hypogonadal men with the AIDS wasting syndrome [ 5 ] . Previous studies in non-HIV-infected hypogonadal men show that and rogen administration has a significant anabolic effect on body composition [ 6 - 10 ] . We hypothesized that loss of the potent anabolic hormone testosterone in men with the AIDS wasting syndrome may contribute to the critical loss of lean body mass . Therefore , we investigated the effects of physiologic testosterone administration in men with the AIDS wasting syndrome . Methods Patients In 1995 and 1996 , 51 HIV-positive men ( 42 8 years of age ) were recruited from the multidisciplinary HIV practice at the Massachusetts General Hospital and from newspaper , television , and radio advertisements .  Weight , testosterone levels , and medication history were determined at a screening assessment . To be included in the study , patients had to have decreased free testosterone levels  , defined as less than 42 pmol/L at screening ( normal range for men 18 to 49 years of age , 42 to 121 pmol/L [ 12.0 to 35.0 pg/mL ] ) , and wasting , defined as weight less than 90 % of ideal body weight or involuntary weight loss greater than 10 % of baseline weight [ 11 ] . The CD4 count was not an inclusion criterion . We excluded patients with severe diarrhea ( > 6 stools/d ) ; hemoglobin value less than 5.0 mmol/L ( < 8 g/dL ) ; platelet count less than 50 000 cells/mm3 ; creatinine concentration greater than 177 mol/L ( > 2 mg/dL ) ; new opportunistic infection within 6 weeks of screening ; use of testosterone  , anabolic steroids , growth hormone , ketoconazole  , or  systemic steroid therapy within 3 months before screening ; or history of prostate cancer . In addition , patients receiving antiretroviral agents , including protease inhibitors , were required to be receiving a stable regimen for at least 6 weeks before study entry . Ten patients were receiving long-term , stable therapy with megestrol acetate for at least 8 weeks before study entry and were equally distributed between the two treatment groups ( 5 in the testosterone group and 5 in the placebo group ) . All patients gave written consent , and the study was approved by the Human Studies Committee of the Massachusetts General Hospital . Protocol Patients were r and omly assigned to receive testosterone enanthate , 300 mg ( Bio-Technology General Corp. , Iselin , New Jersey ) , or placebo intramuscularly every 3 weeks by self-injection . Participants were stratified for weight less than or greater than 90 % of ideal body weight and megestrol acetate use before r and omization . R and omization was performed by the Massachusetts General Hospital Pharmacy by using a permuted block algorithm . The correspondence between patient code number and drug was generated by the study statistician ; this list was available to the hospital pharmacist but not to the investigators or patients . The placebo contained sesame oil with chlorobutanol as a preservative and matched testosterone enanthate in color and consistency . The study drug was bottled by the Massachusetts General Hospital Pharmacy in containers labeled with the study name , expiration date , and patient code . Before the first injection , participants returned within approximately 2 weeks of the screening visit for a 3-day baseline inpatient visit to the General Clinical Research Center at the Massachusetts General Hospital for hormonal , nutritional , immune function , and body composition analysis , which included assessment by dual-energy x-ray absorptiometry , bioimpedance analysis , potassium-4040 K ) isotope analysis , and measurement of urinary creatinine excretion . No patient experienced the onset of a new opportunistic infection , other complication , or substantial weight change between the screening and baseline visits . Patients were instructed on the proper technique for intramuscular injection ; those who were unable to self-administer the study drug received injections every 3 weeks from the nursing staff of the General Clinical Research Center . Patients returned for an outpatient visit at 3 months for assessment of weight and determination of total-body potassium content and for a 3-day inpatient visit at 6 months ; this visit was identical to the baseline evaluation . Patients also reported on response to therapy at the 6-month visit . Baseline data from 26 patients have been reported elsewhere [ 5 ] . Subsequent study visits were timed to correspond to the midpoint between study drug injections . Study drug compliance was confirmed by history , medication diaries , outpatient injection records , empty vial counts , and serum testosterone levels . History of medication use was assessed at each visit . The change in fat-free mass assessed by dual-energy x-ray absorptiometry was the primary clinical end point ; changes in weight , muscle mass , total body potassium content , and quality of life were secondary end points . Body Composition Analysis Body composition was determined by four methods : 1 ) dual-energy x-ray absorptiometry to assess fat and fat-free mass ( Hologic-2000 densitometer , Hologic , Inc. , Waltham , Massachusetts ; precision error , 3 % for fat and 1.5 % for fat-free mass [ 12 ] , 2 ) 40 K isotope analysis to assess  total-body potassium content in a whole-body counter with sodium iodide detectors fixed above and below the patient at the xiphoid level ( Canberra Nuclear , Meriden , Connecticut ; precision error < 2.5 % on the basis of repeated calibration with a known potassium chloride source [ Appendix ] ) , 3 ) urinary creatinine excretion averaged over 3 days ( during which the patient received a meat-free diet ) multiplied by a constant of 18 kg of muscle per gram of urinary creatinine and indexed for height to determine the percentage of predicted muscle mass [ 13 , 14 ] , and 4 ) bioimpedance analysis to determine total-body water content ( Bioelectrical Impedance Analyzer Model BIA-101 , RJL Systems , Clinton Turnpike , Michigan ; correlation with deuterium oxide equivalent to R = 0.99 [ 15 ] ) . Lean body mass was derived from total-body potassium content by using the Equation of Forbes and Lewis of 68.1 mEq of potassium per kg of lean body mass [ 16 ] . Nutritional Assessment Weight was measured on the first day of each visit after an overnight fast . The percentage of ideal body weight was calculated on the basis of st and ard height and weight tables [ 17 ] . Patients were instructed on completion of a 4-day food record , which was analyzed for total calorie , fat , protein , and carbohydrate content ( Minnesota Nutrition Data Systems , version 8A/2.6 , Minneapolis , Minnesota ) by the Clinical Research Center dietitian . Patients received an isocaloric , meat-free , protein-substituted diet 3 days before and during the inpatient assessment s at baseline and at 6 months , during which creatinine excretion and nitrogen balance were measured . Total urinary nitrogen excretion was measured by the Kjeldal technique from consecutive 24-hour collection s averaged over 3 days . Nonurinary nitrogen losses were assumed to be constant at 4 g/d [ 13 , 18 , 19 ] . Nitrogen intake was derived from total protein intake divided by a constant of 6.25 g of protein per g of nitrogen [ 19 ] . Calorie and  protein  intake were monitored on a daily basis and were modified to match the reports in the outpatient food records immediately before these visits . Resting energy expenditure was measured by indirect calorimetry with a metabolic cart . Energy requirements were calculated by using the Harris-Benedict equation [ 20 ] . Patient Reports of Response to Therapy Each patient 's perceived well-being was assessed at the end of the study by using nine linear analogue-scale questions on the overall treatment effect , change in quality of life , personal appearance , weight , and appetite ( Table 1 ) [ 21 ] . A Karnofsky score was also determined at each visit . Table 1 . Assessment of Patient Response to Therapy * Exercise Functional Testing Exercise history was assessed by a st and ardized question naire adapted from the study by Kohl and coworkers [ 22 ] . Exercise functional status was determined at the baseline and final visits by the physical therapy department of the Massachusetts General Hospital by using the 6-minute walk test , the timed sit-to-st and test , and the timed get-up- and -go test [ 23 - 25 ] . The distance covered in 6 minutes , the number of times the patient was able to move from a sitting to st and ing position in 10 seconds , and the time to cover a distance of 3 meters after st and ing from a seated position was recorded for each patient . Biochemical and Immunologic Assays Hematocrit and serum levels of follicle-stimulating hormone , luteinizing hormone , sex hormone-binding globulin , and prolactin were measured at the baseline and final visits by using published methods [ 26 ] . Serum levels of total and free testosterone were measured by radioimmunoassay kit ( Diagnostics Products Corp. , Los Angeles , California ) with intra-assay coefficients of variation of 5 % to 12 % for total testosterone and 3.2 % to 4.3 % for free testosterone . CD4 cell counts were measured by flow cytometry ( Becton Dickinson Immunocytochemistry Systems , San Jose , California ) . Viral burden was determined by using the Amplicor HIV-1 monitor test ( Roche Molecular Systems , Branchburg , New Jersey ) . Statistical Analysis Sample size was based on the change in lean body mass in response to testosterone administration among adult men with acquired hypogonadism [ 8 ] . A change of 3.2 % 4.0 % was expected over 6 months . With 20 patients in each group , the study had an 80 % chance of seeing an effect of testosterone at a
Testosterone supplementation did not show consistent benefit for cardiovascular risk , sexual function , mood and behavior , or cognition .
Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo .
Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido .
Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function .
Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality , psychological well-being , or mood .
Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of " low testosterone " ( low-T ) for cardiovascular health , sexual function , muscle weakness or wasting , mood and behavior , and cognition .