Anabolic steroids for treating pressure ulcers.

BACKGROUND: Pressure ulcers, also known as bed sores, pressure sores or decubitus ulcers develop as a result of a localised injury to the skin or underlying tissue, or both. The ulcers usually arise over a bony prominence, and are recognised as a common medical problem affecting people confined to a bed or wheelchair for long periods of time. Anabolic steroids are used as off-label drugs (drugs which are used without regulatory approval) and have been used as adjuvants to usual treatment with dressings, debridement, nutritional supplements, systemic antibiotics and antiseptics, which are considered to be supportive in healing of pressure ulcers. Anabolic steroids are considered because of their ability to stimulate protein synthesis and build muscle mass. Comprehensive evidence is required to facilitate decision making, regarding the benefits and harms of using anabolic steroids. OBJECTIVES: To assess the effects of anabolic steroids for treating pressure ulcers. SEARCH METHODS: In March 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) comparing the effects of anabolic steroids with alternative treatments or different types of anabolic steroids in the treatment of pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently carried out study selection, data extraction and risk of bias assessment. MAIN RESULTS: The review contains only one trial with a total of 212 participants, all with spinal cord injury and open pressure ulcers classed as stage III and IV. The participants were mainly male (98.2%, 106/108) with a mean age of 58.4 (standard deviation 10.4) years in the oxandrolone group and were all male (100%, 104/104) with a mean age of 57.3 (standard deviation 11.6) years in the placebo group. This trial compared oxandrolone (20 mg/day, administered orally) with a dose of placebo (an inactive substance consisting of 98% starch and 2% magnesium stearate) and reported data on complete healing of ulcers and adverse events. There was very low-certainty evidence on the relative effect of oxandrolone on complete ulcer healing at the end of a 24-week treatment period (risk ratio RR) 0.81, 95% confidence interval (CI) 0.52 to 1.26) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, we are uncertain whether oxandrolone improves or reduces the complete healing of pressure ulcers, as we assessed the certainty of the evidence as very low.There was low-certainty evidence on the risk of non-serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 3.85, 95% CI 1.12 to 13.26) (downgraded once for imprecision and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, the treatment with oxandrolone may increase the risk of non-serious adverse events reported in participants.There was very low-certainty evidence on the risk of serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 0.54, 95% CI 0.25 to 1.17) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Of the five serious adverse events reported in the oxandrolone-treated group, none were classed by the trial teams as being related to treatment. We are uncertain whether oxandrolone increases or decreases the risk of serious adverse events as we assessed the certainty of the evidence as very low.Secondary outcomes such as pain, length of hospital stay, change in wound size or wound surface area, incidence of different type of infection, cost of treatment and quality of life were not reported in the included trial.Overall the evidence in this study was of very low quality (downgraded for imprecision and indirectness). This trial stopped early when the futility analysis (interim analysis) in the opinion of the study authors showed that oxandrolone had no benefit over placebo for improving ulcer healing. AUTHORS' CONCLUSIONS: There is no high quality evidence to support the use of anabolic steroids in treating pressure ulcers.Further well-designed, multicenter trials, at low risk of bias, are necessary to assess the effect of anabolic steroids on treating pressure ulcers, but careful consideration of the current trial and its early termination are required when planning future research.

Alcoholic hepatitis: a clinician's guide.

Alcoholic hepatitis is a frequent reason for admission and a common consultation request for hepatologists and gastroenterologists. Although it seems to occur acutely, it is usually subacute and often superimposed on underlying alcoholic cirrhosis. Typically patients have a background of drinking on a daily basis, but, in response to a life crisis, patients have started drinking massively.

Enfoque terapéutico global de la sarcopenia / Global therapeutica approach to sarcopenia

La sarcopenia es la pérdida de masa muscular esquelética asociada al envejecimiento, y contribuye en gran medida a la discapacidad y la pérdida de independencia del anciano. En su etiopatogenia se incluyen diversos mecanismos tanto intrínsecos del propio músculo como cambios a nivel del sistema nervioso central, además de factores hormonales y de estilo de vida. Diversas hormonas y citoquinas afectan la función y la masa muscular. La reducción de testosterona y estrógenos que acompaña la vejez aceleran la pérdida de masa muscular. La hormona de crecimiento también se ha implicado en la pérdida de masa magra corporal. Aunque la sarcopenia no revierte completamente con el ejercicio, la inactividad física acelera la pérdida de la masa muscular. El diagnóstico de sarcopenia está dificultado por la falta de disponibilidad de los métodos más fiables para medir la masa muscular Se han ensayado diversas estrategias para su tratamiento: tratamiento sustitutivo con testosterona / otros andrógenos anabolizantes, estrógenos en mujeres, hormona de crecimiento, tratamiento nutricional y ejercicio físico. De todas las alternativas terapéuticas, sólo el ejercicio físico de resistencia ha demostrado su eficacia en incrementar la masa muscular esquelética, asociado o no a suplementación nutricional (AU)

Sarcopenia is the loss of skeletal muscle mass that occurs with ageing, and is a major contributing factor to disability and loss of independence in the elderly. The etiopathogenesis involves a number of underlying mechanisms including intrinsic changes in the muscle and central nervous system, and hormonal and lifestyle factors. Many hormones and cytokines affect muscle mass and function. Reductions in testosterone and estrogens that accompany ageing appear to accelerate loss of muscle mass. Growth hormone has been hypothesised to contribute to loss of lean body mass. Although sarcopenia is not completely reversed with exercise, physical inactivity leads to accelerated muscle loss. The diagnosis of sarcopenia is difficult because the most reliable methods to measure muscle mass are not easily available. Various treatment strategies have been tested for combating the loss of muscle mass: testosterone replacement and other anabolic androgens for men, estrogen replacement in women, growth hormone replacement, nutritional treatment and physical training. Only high resistance exercise training has been effective in increasing muscle mass, with or without nutritional supplementation (AU)

Vitamin A and iron supplementation is as efficient as hormonal therapy in constitutionally delayed children.

OBJECTIVE: To assess the effect of nutritional supplementation on growth and puberty in constitutionally delayed children. PATIENTS: One hundred and two boys, 13.6-15.5 years of age, who were referred because of short stature and delayed puberty. METHODS: The boys were randomly allocated to one of the following treatment groups: oxandrolone therapy, 5 mg/day for 6 months (n = 15), testosterone depot, 100 mg monthly for 3 months (n = 15) or for 6 months (n = 20), nutritional programme (n = 17), oxandrolone and nutritional programme (n = 15) or passive observation (n = 20). Boys in the nutritional programmes received 12 mg/day iron and 6000 IU/week of vitamin A. Outcome measurements were of height, weight, pubertal signs, dietary intake, serum vitamin A, iron, GH and IGF-1. RESULTS: Six months of vitamin A supplementation induced growth acceleration similar to that seen in the oxandrolone- and testosterone-treated children, and significantly greater than in the observation group (9.3 +/- 2.9 vs. 4.0 +/- 0.9 crn/yr, P < 0.001). Whereas in the vitamin A-supplemented group, puberty (increase in testicular volume >/= 12 ml) was induced within 12 months. In all testosterone-treated patients, pubic hair was noted within 3 months and a testicular volume of >/= 12 ml was observed 9-12 months after the initiation of therapy. No pubertal signs were noted in the observation group during this time. CONCLUSIONS: Subnormal vitamin A intake is one of the aetiological factors in delayed pubertal maturation. Supplementation of both vitamin A and iron to normal constitutionally delayed children with subnormal vitamin A intake is as efficacious as hormonal therapy in the induction of growth and puberty.

The long-term effect of oxandrolone on hepatic acute phase proteins in severely burned children.

BACKGROUND: Acute phase protein production is a hallmark of severe burns. We wondered whether anabolic treatment with oxandrolone would affect these proteins. METHODS: Thirty-five children with > or =40% total body surface area burns were randomized to receive either placebo or oxandrolone (0.1 mg/kg by mouth twice daily) from postoperative day 5 to 1 year postburn. Levels of constitutive proteins and acute phase proteins were measured at admission; at discharge; and at 6, 9, and 12 months after burn. Total albumin supplementation and hepatic transaminases were also assessed. RESULTS: Constitutive proteins such as albumin, prealbumin, and retinol-binding protein levels increased (p < 0.05), and acute phase proteins such as alpha 1-acid glycoprotein, C3 complement, alpha 2-macroglobulin, and fibrinogen levels significantly decreased in the oxandrolone group compared with placebo (p < 0.05). Albumin supplementation during the acute hospitalization was reduced in the oxandrolone group. Hepatic transaminases remained within normal levels. CONCLUSION: Treatment with oxandrolone in severe burns significantly increases constitutive protein and reduces acute phase protein levels.

A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study.

A Veterans Affairs cooperative study involving 273 male patients was performed to evaluate efficacy of oxandrolone in combination with an enteral food supplement in severe alcoholic hepatitis. All patients had some degree of protein calorie malnutrition. On an intention-to-treat basis, only minimal changes in mortality were observed. However, in patients with moderate malnutrition mortality on active treatment at 1 mo was 9.4% compared with 20.9% in patients receiving placebo. This beneficial effect was maintained so that after 6 mo on active treatment 79.7% of patients were still alive, compared with 62.7% of placebo-treated patients (p = 0.037). Improvements in both the severity of the liver injury (p = 0.03) and malnutrition (p = 0.05) also occurred. No significant improvement was observed with severe malnutrition. To better determine the effect on therapeutic efficacy, we compared results with those from a nearly identical population (cooperative study 119) treated with oxandrolone but not given the food supplement. Patients were stratified according to their caloric intake (greater than 2,500 kcal/day was considered adequate to supply energy needs and promote anabolism). For patients with moderate malnutrition and adequate caloric intake, oxandrolone treatment reduced 6-mo mortality (4% active treatment vs. 28% placebo [p = 0.002]). For patients with moderate malnutrition and inadequate calorie intake, oxandrolone had no effect on mortality (30% active treatment vs. 33% placebo). In cases of severe malnutrition, oxandrolone had no effect on survival. However, adequate caloric intake was associated with 19% mortality, whereas patients with inadequate intake exhibited 51% mortality (p = 0.0001). These results indicate that nutritional status should be evaluated in patients with alcoholic hepatitis. When malnutrition is present, vigorous nutrition therapy should be provided, and in patients with moderate malnutrition oxandrolone should be added to the regimen.

A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. II. Short-term effects on nitrogen metabolism, metabolic balance, and nutrition.

Patients with moderately severe or severe alcoholic hepatitis, described in a companion paper in this issue, had serial studies of energy and protein metabolism and elemental balances before and during treatment for 21 days with one of four randomly assigned regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 liters of 3.5% crystalline amino acids in 5% dextrose given by peripheral vein (PPN) plus standard therapy; and 4) a combination of the other three treatments. Dietary and intravenous intakes and weights were recorded daily, and weekly averages were calculated. Anthropometric measurements and blood studies were done weekly; blood studies included white blood cell counts and differentials, serum prealbumin, transferrin, and total protein and plasma aminograms. Four-days complete balance studies and measures of 15N,1-13C-leucine metabolism also were performed at baseline and after the treatment period. Major findings were as follows: a) Intakes of total calories and protein were significantly higher in PPN-treated than in other groups. b) All patients had positive elemental balances, both at baseline and at the end of the treatment period. However, those treated with PPN (with or without oxandrolone) had higher positive balances of nitrogen, potassium, phosphorus, and magnesium, indicating improvement in lean body mass. c) Anthropometric measurements showed no significant changes, but measures of the visceral protein compartment (serum prealbumin, transferrin, total protein, total lymphocyte count) improved significantly with time. For most of these variables, increases were significantly greater in those treated with PPN with or without oxandrolone than in the other groups. However, for prealbumin, the increase was greatest in the oxandrolone-treated group d) PPN treatment produced dramatic increases in levels of branched-chain amino acids and improvement in the ratio of plasma branched chain to aromatic amino acids. Other treatments had no effect on plasma aminograms. e) Metabolism of 15N,1-13C-leucine was normal and was not affected significantly by treatment. Therapy with PPN and/or oxandrolone was tolerated well. We conclude that PPN has favorable effects on energy and protein metabolism in florid alcoholic hepatitis; oxandrolone has lesser effects, although it may exert some additional action and particularly increases serum prealbumin levels. The results support the use of nutritional supplementation in therapy of moderately severe or severe alcoholic hepatitis.

A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. I. Short-term effects on liver function.

The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's-Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35-day three-phase protocol. Phase I was a 10-day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7-day elemental balance study, and a 15N, 13C-leucine metabolism study were done. Phase II was a 21-day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 L daily of 3.5% crystalline amino acids (in 5% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase II. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured.

Efficacy and interactions of oxandrolone, halo-fenate and clofibrate in a factorial study on experimental acute nephrotic hyperlipidemia.

Nephrotic mixed hyperlipidemia may be associated with accelerated coronary artery disease. To investigate the response of experimental nephrotic hyperlipidemia to therapy, a 2(4) factorial study of sodium clofibrate and beta-benzalbutyrate, halofenate and oxandrolone (250, 150, 100 and 10 mg/kg/day, respectively) was carried out. Nephrotic syndrome was induced by a single i.p. injection of puromycin aminonucleoside (90 mg/kg) in 80 female white rats of average weight 160 g. Oxandrolone proved to be significantly hypotriglyceridemic in combined therapy (average fall, 38%; P less than .05), and also lowered serum total cholesterol and phospholipid concentrations (23% and 21% falls, P less than .01) and less than .05), due largely to synergistic interactions with clofibrate-like drugs. Hypocholesteremic effects (23 and 22% average falls) were also significant for halofenate (P less than .01) and clofibrate (P less than .05) . Serum triglyceride levels actually rose significantly (P less than .05) with drug combinations containing beta-benzalbutyrate. Clofibrate and its analogs (halofenate and beta-benzalbutyrate) produced significant hepatomegaly (mean responses of +18, +18 and +10%, respectively) whereas oxandrolone produced significant hepatic shrinkage (-10%)(P less than .05). Secondary effects (drug interactions) were also found; hypotriglyceridemic synergism (effects more than additive) occurred between oxandrolone and clofibrate or its analogs (P less than .05), whereas antagonism (effects less than additive) was observed within the clofibrate-like group (P less than .01 or less .05).

Short- and long-term effects of estrogen and synthetic anabolic hormone in postmenopausal osteoporosis.

In 29 women with postmenopausal osteoporosis, the proportion of total bone surface undergoing resorption or formation was evaluated by microradiography of iliac crest biopsy samples before and after short-term (2(1/2)-4 months) and long-term (26-42 months for estrogen and 9-15 months for anabolic hormone) treatment. After estrogen administration, values for bone-resorbing surfaces decreased, although less prominently after long-term than after short-term therapy. The magnitude of this decrease was positively correlated with the pretreatment value for bone-resorbing surfaces (P < 0.001). When the pretreatment value for bone-resorbing surfaces was used as a covariable, estrogen and anabolic hormone appeared to be equally effective. For bone-forming surfaces, short-term therapy with either hormone had no effect but long-term therapy significantly decreased the values. Serum immunoreactive parathyroid hormone (IPTH) increased significantly after estrogen therapy; the change in IPTH was inversely related to the change in serum calcium (P < 0.001, sign test). We conclude that the primary effect of sex hormones in postmenopausal osteoporosis is to decrease the increased level of bone resorption, perhaps by decreasing the responsiveness of bone to endogenous parathyroid hormone. However, this favorable effect, at least in part, is negated after long-term treatment by a secondary decrease in bone formation. Our data are consistent with the concept that the maximal benefit that can be derived from sex hormone therapy in postmenopausal osteoporosis is arrest or slowing of the progession of bone loss.