NandroloneIglesias; Nandrolone decanoate may be an adjuvant therapy to nandrolone renal failure haemoglobin response today? We have nandrolone renal failure with great interest the article by Macdougall on how to optimize the use of recombinant human erythropoietin r-HuEpo. We suggest that nandrolone decanoate nandro,one be another deca tel aviv tripadvisor therapy in elderly male patients on haemodialysis HDsimilar to nandrolone renal failure -carnitine. A retrospective study in HD patients concluded that the anaemia response to nandrolone decanoate is related to the age of patients and independent of sex, time on dialysis, or aetiology of chronic renal failure [ 2 ]. Moreover, recent studies have reconsidered the use of this treatment in uraemic patients [ 34 ]. The erythropoietic nandrolone renal failure of nandrolone decanoate is mediated by direct stimulation of renal erythropoietin production or by nandrolone renal failure the sensitivity of erythroid progenitor cells in the bone marrow to the circulating erythropoietin [ 5 ].
Anabolic steroids are known to increase muscle mass and strength in healthy individuals, but their effect on the sarcopenia and fatigue associated with long-term dialysis has not been evaluated. Time to complete the walking and stair-climbing test decreased from Peak oxygen consumption increased in the individuals in the nandrolone group who performed treadmill tests, but not to a statistically significant degree.
Grip strength did not change in either group. In the United States, the average life span of a patient entering a long-term dialysis program is less than half that of an age-matched control not receiving dialysis. Anabolic agents, such as human growth hormone, can improve nitrogen balance in patients undergoing dialysis and in other catabolic states. Moreover, human growth hormone is expensive and may have limited potential as a long-term treatment. Anabolic steroids, such as nandrolone decanoate, might be expected to accomplish some of the same anabolic effects of human growth hormone without leading to hyperglycemia.
Nandrolone and other anabolic steroids have been used by athletes to build muscle mass and enhance weight-lifting performance, and a recent placebo-controlled study showed that supraphysiologic dosages of testosterone resulted in an increase in muscle mass and strength in normal subjects. Furthermore, the widespread availability of recombinant human erythropoietin for the treatment of anemia associated with chronic renal failure has virtually eliminated the use of nandrolone in dialysis patients in the United States.
The present study was undertaken to determine whether a 6-month course of nandrolone could improve nutritional and functional status in patients undergoing dialysis, using a randomized, double-blind, placebo-controlled design.
Changes in lean body mass LBM measured by dual-energy x-ray absorptiometry DEXA , treadmill exercise performance, walking and stair-climbing tests, and several quality-of-life measures were compared in the groups receiving nandrolone and placebo. Entry criteria included evidence of malnutrition by biochemical indexes or body composition measurements, or poor quality of life as assessed by questionnaire. Specifically, patients had to have 2 or more of the following to be considered malnourished: Patients were excluded if they had been receiving dialysis for fewer than 3 months or if they had other reasons for being in a catabolic state, such as human immunodeficiency virus HIV infection, known malignancy, corticosteroid treatment, surgery, or infection requiring intravenous antibiotics, within 3 months.
Other exclusion criteria included participation in other studies or illicit drug use. All patients gave written informed consent for study participation and the protocol was approved by the Committee on Human Research at the University of California, San Francisco.
Study subjects underwent an initial evaluation in the General Clinical Research Center GCRC at San Francisco General Hospital that included a history taking and physical examination, measurements of body composition, tests of strength and endurance, and an assessment of physical performance and quality of life.
Hemodialysis patients with edema had their dry weights adjusted until they were free of edema and had no orthostatic changes at the end of dialysis. Baseline measurements of indexes of nutritional status, including serum urea nitrogen, serum creatinine, albumin, total cholesterol, and transferrin levels, were performed by Spectra Laboratories, Fremont, Calif, and total and free testosterone, luteinizing hormone, follicle-stimulating hormone, and IGF-1 in the core laboratory of the GCRC using reagents purchased from Diagnostic Products Corp Los Angeles, Calif and Nichols Institute Diagnostics IGF-1, San Juan Capistrano, Calif.
These measurements were made within 1 hour after hemodialysis or following drainage of peritoneal dialysis fluid. Patients wore only a hospital gown, underwear, and pajama bottoms that contained no snaps or other material that might interfere with attenuation.
The same equipment was used for baseline, 3-month, and 6-month evaluations for all patients. Patients without a history or symptoms of coronary artery disease or physical limitations to exercise underwent functional testing.
A treadmill protocol that was designed for patients with limited ability to exercise was used. Heart rate and blood pressure were monitored throughout the test, and the test was terminated when the patient expressed his or her inability to exercise further or when systolic blood pressure exceeded mm Hg or diastolic blood pressure measured mm Hg.
Each hand was tested 3 times and the highest value was recorded. A walking and stair-climbing test was performed in the 16 hemodialysis subjects who were enrolled after May Subjects were timed while walking a fixed distance at a normal pace and while climbing a flight of stairs at a normal pace, and the results were summed.
Quality of life was assessed by an instrument administered by personal interview. Randomization was computer-generated in blocks of 4. Assignments were made sequentially by a research pharmacist who dispensed medications but was not otherwise involved in the study. Patients were given their injections at the dialysis unit by GCRC staff. Dialysis staff, patients, and investigators were blinded throughout the study to treatment assignment.
Hematocrit and hemoglobin levels were measured monthly and erythropoietin dosages were adjusted to maintain hematocrit between 0.
Monthly liver function tests were checked, and the dosage of study drug was reduced by half for any elevation of transaminases to more than 3 times the upper limit of normal. Dosages were also reduced for signs of virilization. After 3 and 6 months of treatment, patients returned to the GCRC for repeat testing of quality of life, body composition, functional performance, and hormone levels.
Sample size was determined using change in LBM as the primary outcome measure and extrapolating expected changes and SDs from data in patients with HIV-associated wasting.
Comparisons between groups were made by unpaired t tests. Changes between baseline and follow-up variables within each group were compared with paired t tests. Univariate correlations were evaluated using Pearson regression analysis. Variables are reported as mean SD unless otherwise noted. All subjects who met the entry criteria were asked to participate. The most frequent reasons for ineligibility included recent access surgery or infection, inadequate length of dialysis treatment, infection with HIV, and inability to give consent.
Six subjects who were otherwise eligible declined to participate in the study Figure 1. A total of 29 subjects were enrolled Table 1. Fourteen subjects received nandrolone and 15 received placebo injections. The treatment groups were quite similar, with no statistically significant differences in any of the parameters tested. The underlying cause of end-stage renal disease was diabetes in 11 subjects, hypertension in 9, nephrolithiasis and chronic pyelonephritis in 1, and unknown in the remaining 8.
All but 1 subject required antihypertensive treatment at the time of study enrollment. A total of 6 women 2 premenopausal were included in the study. Twenty-five subjects completed the 6-month protocol and 23 of these 12 in the nandrolone group and 11 in the placebo group had all measurements made. Two subjects completed the study but were unable to have final measurements taken because of medical instability. Three subjects were withdrawn from the placebo group because of elevated transaminases at 4 weeks , hematoma at the study drug injection site at 3 months , and sudden death at 4 months.
One subject in the nandrolone group was withdrawn after developing unstable angina at 3 weeks. Changes in body composition are shown in Figure 2. By the end of the study, subjects who received nandrolone had gained 1.
These data do not include changes in body weight for 2 patients, 1 of whom had a leg amputation and the other, a central venous stenosis resulting in massive arm edema. In these subjects, calculation of the changes in body composition excluded the affected limbs.
Results are qualitatively similar if these 2 patients are excluded from the analysis. Although there was no significant difference in the change in body weight between the groups, there were significant differences in the components of body composition. The nandrolone group gained 4. Fourteen subjects were able to undergo paired treadmill tests at baseline and 3 months and 11 subjects completed treadmill testing at baseline and after 6 months of treatment.
Reasons for inability to undergo initial or follow-up treadmill testing included coronary artery disease 7 subjects ; hospitalization at the time of planned evaluation 3 subjects ; severe hypertension on the day of intended testing 2 subjects ; study drop-out 2 subjects ; and valvular heart disease, amputation, arthritis, abdominal hernia, and diabetic foot ulcer 1 subject each.
Table 2 shows the exercise data. For all variables, the difference between the nandrolone and placebo groups was statistically significant at 3 months but not at 6 months. However, the difference at 3 months appeared to be due to both improvement in the nandrolone group and deterioration in the placebo group. There was no significant improvement in the nandrolone group compared with baseline after 3 or 6 months of treatment.
Walking and stair-climbing times improved significantly in the nandrolone group compared with the placebo group after 6 months Table 2. There were no changes in grip strength in either group. Total serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels decreased significantly in men who received nandrolone but not in men who received placebo Table 3.
Free testosterone levels also decreased in the group receiving nandrolone, but not to a statistically significant degree. There were no changes in dehydroepiandrosterone sulfate or estradiol levels.
Too few women were enrolled to draw conclusions about changes in hormone levels with nandrolone. Hematocrit did not change significantly during the study in either group because erythropoietin dosage was adjusted to maintain hematocrit.
By the end of the study, erythropoietin dosage had been reduced significantly in the group as a whole, but there was no significant difference in magnitude of the reduction between the nandrolone and placebo groups. Total cholesterol levels decreased by 0. Cholesterol levels were not fractionated because the samples were not all collected under fasting conditions. Nevertheless, there were no changes in triglyceride levels in either group.
Quality-of-life data were available in 19 patients 11 in the nandrolone group and 8 in the placebo group. The only significant change in quality of life was a reduction in the fatigue component of the Profile of Mood States in the nandrolone group at 6 months from 6.
The study drug was generally well tolerated, but minor adverse effects occurred. Two subjects 1 receiving nandrolone and 1 receiving placebo developed a hematoma at the injection site. In both cases, the hematoma resolved spontaneously. One nandrolone recipient complained of a reduction in testicular size that resolved with dosage reduction. Two men both receiving placebo injections complained of skin rash that did not resolve after the drug was discontinued. Of the 3 women who received nandrolone, 2 required dosage reduction for amenorrhea and acne, respectively.
Nandrolone did not appear to affect blood pressure control. All but 1 subject were receiving antihypertensive therapy. Six subjects required increases in antihypertensive medication during the study 3 in each group. Seven subjects had their antihypertensive medication dosages reduced during the study 4 receiving nandrolone and 3 receiving placebo. The results of the present study demonstrate that treatment with nandrolone leads to anabolic effects and functional benefit in debilitated dialysis patients.
During a 6-month treatment period, subjects who received nandrolone gained an average of 2. This gain was accompanied by an increase in serum creatinine levels, suggesting that nandrolone caused increased muscle mass. In addition, subjects who received nandrolone had a significant reduction in their reported symptoms of fatigue and a decrease in the times required for walking and stair-climbing.
Several short-term studies have examined the effects of anabolic agents, such as human growth hormone in patients undergoing dialysis, and have demonstrated positive effects on nitrogen balance. Nandrolone offers several theoretical advantages over human growth hormone in the dialysis population.
Human growth hormone has the potential to exacerbate hyperglycemia in patients with diabetes 21 , 22 and, because patients with diabetes make up a disproportionate number of the malnourished and debilitated dialysis patients most likely to benefit from anabolic therapy, human growth hormone may have limited utility.