Pharmacological action of anabolic steroids

Anabolic steroids (AS) are derivatives of androgen (testosterone and its close relatives). AS have been primarily developed for clinical use as anabolic agents with the expectation that they would be relatively less androgenic than testosterone and its close relatives. Various AS are applied to clinical use, but none is free from androgenic activity. Relation between chemical structure and anabolic-androgenic potency of various AS is summarized. AS action in erythropoiesis operates through increased porphyrin formation and production of erythropoietin. Mechanism of AS action in bone formation is suggested that AS potentiate intestinal 1.25(OH)2D receptors. Identification of androgen receptors in normal human osteoblast-like cells suggest that AS act directly on receptor-mediated mechanism. The other action of AS is briefly summarized.     

Miscellaneous uses of anabolic steroids

The endocrine side effects are mainly androgenic and concern particularly but not exclusively females and children. Depending on individual sensitivity, the dosage used and the androgenicity of the drug concerned, signs of virilization ranging from slight voice disturbances to severe derangement of reproduction can develop, the latter occurring in both sexes. Progestational effects are of little importance. Hepatic alterations are caused almost exclusively by 17 alpha-alkylated steroids and can range from abnormal liver function tests to life-threatening liver tumours. Atherogenic changes in the lipid-lipoprotein balance, again a domain of the 17 alpha-alkylated preparations, might increase the risk of coronary heart disease. The metabolic influences of anabolic compounds can--at excessive dosage levels--create a prediabetic condition and polycythaemia. The influence of anabolic agents on psyche and behavior in normal doses are mostly positive, rendering the drugs useful for adjuvant therapy in patients whose general condition is poor, irrespective of the origin. If given in excessive doses they can cause grave psychic and behavioral disturbances and possibly dependence. Anabolic-androgenic steroids should be used with caution in patients who are particularly sensitive to side effects, where fluid retention must be prevented, in subjects with liver diseases, skeletal metastases of mammary carcinoma, and when longitudinal growth is not completed. They are contraindicated in carcinoma of the prostate and mammary carcinoma in the male and their use should be discouraged in pregnancy and during lactation.     

Metabolism of anabolic androgenic steroids

Anabolic androgenic steroids (AAS) are misused to a high extent in sports by athletes to improve their physical performance. Sports federations consider the use of these drugs in sports as doping. The misuse of AAS is controlled by detection of the parent AAS (when excreted into urine) and (or) their metabolites in urine of athletes. I present a review of the metabolism of AAS. Testosterone is the principal androgenic steroid and its metabolism is compared with that of AAS. The review is divided into two parts: the general metabolism of AAS, which is separated into phase I and phase II metabolism and includes a systematic discussion of metabolic changes in the steroid molecule according to the regions (A-D rings), and the specific metabolism of AAS, which presents the metabolism of 26 AAS in humans.     

Treatment of myasthenic patients with anabolic steroids

The authors report of their observations over 52 patients with severe and moderate myasthenia who after diverse forms of therapy (thymusectomy, x-ray therapy, prolonged use of anticholesterase preparations, etc.) did not demonstrate a stable therapeutical effectiveness. However, treatment by retabolil proved to be effective with minimal side effects. The paper contains theoretical prereqisites to therapy by anabolic hormones and the approximate scheme of its use.     

Azoospermia in 2 body-builders after taking anabolic steroids

During investigations for infertility azoospermia was diagnosed in two men who were concomitantly using anabolic steroids for body-building. Following cessation of anabolic steroid use the semen quality was normalized. Suppression of spermatogenesis during treatment with testosterone and derivatives hereof is wellknown. Usage of anabolic steroids should be remembered as a cause of oligo- and azoospermia and asked about in cases of sperm counts approaching or at zero.     

The role of anabolic steroids on baseline and stress heart rate in cynomolgus monkeys.

This investigation examined the role of anabolic steroids on baseline heart rate (HR) and HR responses to the threat of capture in Macaca fascicularis. Ten cynomolgus monkeys were randomly assigned either to a steroid or to a sham control group. Steroid-treated animals were given testosterone injections biweekly for 10 weeks, whereas sham controls received injections of sesame oil on an identical schedule. Pretreatment and posttreatment HRs were evaluated to establish both baseline and acute-stress responses. Results revealed that animals given testosterone experienced a statistically significant increase in baseline HR when contrasted with the sham controls. No difference between the groups was detected in response to the threat of capture. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of anabolic steroids on driving performance as assessed by the Iowa Driver Simulator

The effect of physiologic (100 mg/wk) and supraphysiologic (250 and 500 mg/wk) doses of testosterone cypionate (TC) on automobile driving were studied using the Iowa Driver Simulator. Six normal subject volunteers were studied off TC and on TC once steady-state concentrations were achieved after at least three weeks of dosing. Despite the administration of supraphysiologic testosterone doses, an increase in aggressive driving behavior was not detected. Likewise, corresponding psychometric testing using the Buss-Durkee Hostility Inventory to assess aggression was unable to detect any change in aggression in the test subjects. Although aggressive driving behavior may be increased by testosterone administration, the drug itself may not be responsible for these effects. Supraphysiologic doses greater than 500 mg/wk and a semi-controlled research environment may be necessary to produce this effect since case reports of AAS abuse causing altered driving behavior may be multifactorial in nature.     

Pharmacological action of 101-B hair regeneration extract on skin and hair in experimental animals

Pharmacological action of 101-B hair regeneration extract (101-B) on skin and hair was studied in experimental animals. The results were as follows: (1) In normal rats, guinea pigs and rabbits the weight of regrown hairs in shaved area in 101-B group was significantly heavier than that in alcohol group. (2) Hair loss induced by oral administration of thallium carbonate 2 mg/kg every other day for 10 times was obviously prevented by topical treatment of 101-B. (3) Itching threshold to histamine or papain in guinea pig was elevated after using of 101-B topically. (4) The diameter of skin ulcer caused by intradermal injection of adriamycin in rats was diminished in 101-B group. (5) Observation in skin microcirculation in mice indicated that both normal skin microcirculation and disturbed microcirculation induced by endotoxin were improved with administration of 101-B. Above experimental results provided preliminary evidence for clinical use of 101-B.     

The use of anabolic steroids by athletes to increase body weight and strength

Over the past 20 years the taking of anabolic steroids by healthy athletes for the purpose of increasing body weight and strength has become very widespread. The ability of these agents to cause potentially serious side effects is discussed. In a series of 20 subjects studied over 18 months, no side effects of significance were recorded, and marked increases in strength and body weight were achieved.     

Lipoprotein (a) and cholesterol in body builders using anabolic androgenic steroids

A 67-year-old Taiwanese woman with multilocular hydatid cysts of the liver presented with a 5-month history of intermittent right upper abdominal discomfort. Abdominal ultrasonography and computed tomography showed multiple cysts in both lobes of the liver. Subsequent selective celiac angiography revealed an avascular space-occupying lesion in the right lobe. She underwent a radical excision of the cyst by total closed (without opening the wall) cystopericystectomy over segments 4, 5 and 6. Histologic study of the lesions showed three structural components: 1) an outer acellular laminated membrane, 2) a thin nucleated germinal membrane and 3) several protoscolices with Echinococcus granulosus suckers. The patient has been well for 5 years since her discharge. Although hydatid cysts of the liver are extremely rare in Taiwan, they may cause life-threatening complications and mortality. Making a preoperative diagnosis is important and is only possible if this rare disease is kept in mind.     

Non-genomic action of steroids in the nervous system

Past research on the importance of 'soft' neurological signs in schizophrenia has often not examined the relationship between specific groups of neurological signs and different dimensions of schizophrenia psychopathology. Gender differences in the reported relationships have never been explored. In this paper we describe a study of 100 DSM-III-R (65 male and 35 female) schizophrenic patients who were rated for neurological 'soft signs' with the Neurological Evaluation Scale (NES) (1), and for schizophrenic symptomatology with the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS). Following a factor analysis of NES items, differential relationships were examined between the five derived NES factors and three well-established dimensions of schizophrenic symptomatology, namely psychomotor poverty, disorganization and reality distortion. Our results failed to show any relationship between NES dimensions and either the reality distortion or disorganization dimensions. There was a modest but differentially significant relationship between psychomotor poverty and an extrapyramidal factor on the NES. This relationship was shown only by male subjects, and was influenced by duration of illness but not by age or neuroleptic medication. On the other hand, female subjects showed a significant relationship between psychomotor poverty and an NES factor reflecting attention and initiative, and between reality distortion and coordination/sequencing of motor activity. These relationships in female subjects were, relative to relationships for male subjects, more independent of the effect of medication and duration of illness.     

The actions of exogenous dehydroepiandrosterone in experimental animals and humans

Dehydroepiandrosterone (DHEA) is the major adrenal steroid of young adults; however, its physiologic functions, if any, are not known. The purpose of this review is to evaluate the current literature in which DHEA was administered to either humans or experimental animals to discern what these functions might be. Reports are divided into five areas: neurologic, immunologic, cardiovascular, oncologic, and metabolic. Particular attention is paid to the dosage and route of administration. This type of analysis shows that at the lowest doses, DHEA has effects on neurologic and immunologic tissues, suggesting that these two sites may be physiologic targets. DHEA also affects cardiologic and metabolic functions as well as tumor growth, but such actions require higher doses and may reflect 'pharmacologic' activities. It is proposed that DHEA's pattern of activity represents a new class of steroid hormones, the "Regnantoids." Further progress in the endocrinology of this family of steroids may only come when synthetic, long-acting analogs of DHEA are available for in vitro studies to allow correlations between hormone action and receptor binding.     

Pharmacokinetics of rifampicin in experimental animals]

Rifampicin is rapidly absorbed when administered orally. Its high levels were detected during 1 to 3 hours after administration. The antibiotic was preserved in the blood serum in therapeutic concentrations for at least 24 hours depending on the dose used. When used repeatedly, it did not cumulate. Rifampicin easily penetrated into the organs and tissues of the animals, the highest concentrations being observed in the liver and kidneys. The antibiotic was mainly excreted with the bile. The drug pharmacokinetics depended on the animal species.     

The cellular mechanism of action of cardiotonic steroids: a new hypothesis

Arterial smooth muscle (ASM) contraction is triggered by agonist-evoked Ca2+ mobilization from sarcoplasmic reticulum (SR). The amount of Ca2+ released, and thus, the magnitude of the contractions, depends directly on SR Ca2+ content. Na+ pump inhibition by cardiotonic steroids (CTS) indirectly increases the Ca2+ content of the SR and, thus, contractility. This sequence of events does not, however, account for the multiple Na+ pump alpha subunit isoforms with different affinities for Na+ and for CTS, nor does it explain the cardiotonic and vasotonic effects of low doses of CTS that do not elevate cytosolic Na+ or Ca2+. We show that the Na+ pump high ouabain affinity (alpha3) isoform and the plasmalemmal (PM) Na/Ca exchanger are confined to PM domains that overlie junctional SR in ASM, while low ouabain affinity alpha1 and the PM Ca2+ pump are uniformly distributed in the PM. Thus, low doses of CTS, including an endogenous ouabain-like compound, influence cytosolic Na+ and (indirectly) Ca2+ concentrations only in the cytoplasmic clefts between the PM and junctional SR (a functional unit we call the "plasmerosome"). In turn, this modulates the Ca2+ content of the junctional SR and cell responsiveness.     

Two cases of acute myocardial infarction associated with aplastic anemia during treatment with anabolic steroids

Thrombosis is a rare complication in patients with aplastic anemia because of the presence of coincidental thrombocytopenia. We have recently treated two cases, a 61-year-old male and a 59-year-old female, with acute myocardial infarction associated with aplastic anemia. Although their platelet counts were lower than normal in spite of treatment with anabolic steroids for aplastic anemia, the coronary angiographic findings strongly suggested coronary thrombosis in both cases. Anabolic steroids, which have been commonly used for the treatment of aplastic anemia, are a possible risk factor for coronary thrombosis because they have an accelerating effect on thrombus formation. We report two very rare but clinically important cases.