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Risk factors of performance-enhancing substances

Risk factors of performance-enhancing substances

Predicting future Recovery meal options steroid use intentions Probiotic-rich foods current substancss use: findings from an internet-based survey. One supplement that's popular with athletes is called creatine monohydrate. quicklist: 11category: Performance-Enhancing Drugs Cheat Sheettitle: Beta-Blockersurl: text: How They Work. Risk factors of performance-enhancing substances

Risk factors of performance-enhancing substances -

AAS exposure affects dopamine receptors in brain areas included in the functional anatomy of aggression , A typical feature seen in individuals taking steroids seems to be a competitive and dominant behavior. Studies have used experimental animal models to better understand the relationship between and AAS use and competitive behavior under various conditions.

For instance, researchers have studied competition and locomotor activity response to a sedative dose of ethanol after AAS exposure in rats The rats treated with AASs exhibited enhanced dominant behavior in the competition test compared with controls.

Ethanol did not affect the AAS groups' locomotor activity, whereas the controls showed decreased locomotor activity. Also, AAS animals had significantly lower levels of serotonin in basal forebrain and dorsal striatum compared with controls.

These results have led to the hypothesis that AAS use may constitute a risk factor for disinhibitory behavior, partly by affecting the serotonergic system.

An additional study on dominant behavior assessed pair-housed male rats for dominance status based on their behavior and alterations in body weights Throughout the study, the rats had limited social interactions on a daily basis.

After 1 week, rats received nandrolone or placebo, and their behavior was observed over 2 months. Dominant AAS-treated rats spent more time on highly aggressive behaviors than the dominant placebo-treated rats. In addition, the probability for highly aggressive behaviors was maintained for the AAS-treated rats throughout the study, whereas it was decreased for the placebo-treated rats.

These observations are similar to the relatively long-term behavioral changes we see in humans after AAS use. Unlike most dependence-inducing drugs, which typically deliver an immediate reward of intoxication, AASs produce few intoxicating effects and are instead taken primarily for the delayed reward of increased muscle mass and decreased body fat.

Despite these differences, AAS dependence may nevertheless become a chronic and potentially dangerous disorder. One group has suggested that AAS dependence may develop via any or all of 3 different pathways, namely a body image pathway, a neuroendocrine pathway, and a hedonic pathway The body image pathway refers to the observation that many individuals initiate AAS use because they exhibit symptoms of muscle dysmorphia, a form of body dysmorphic disorder where individuals develop severe preoccupations that they are not adequately muscular — Muscle dysmorphia appears closely associated with AAS use — Individuals with such concerns often become extremely anxious if they stop AAS use and lose even a little muscular size 45 , 80 , Thus, they often quickly resume AAS, which contributes to the AAS dependence syndrome.

Neuroendocrine factors also contribute to AAS dependence Because exogenous AAS suppresses hypothalamic-pituitary-testicular HPT function , users will gradually develop suppressed testosterone levels and may become hypogonadal upon discontinuation of AAS use.

The associated symptoms of fatigue, loss of libido, and depression may prompt some users to quickly resume using AAS to treat these dysphoric symptoms. Finally, animal studies have provided strong support for a third, hedonic pathway to AAS dependence, likely mediated by nongenomic pathways via membrane receptors rather than by the classical genomic effects of AASs.

Reports that AAS abusers often experience mental effects within 15 to 20 minutes of AAS administration also favor the nongenomic effects through membrane receptors rather than the classical androgen receptor-mediated genomic effects.

In fact, studies have reported steroid binding sites on both GABA and the N- methyl- d -aspartate neurons Studies have also reported interaction of AAS with σ-receptors The function of these receptors remains poorly understood, although there is some overlap with the opioid system , These sites are recognized by neurosteroids produced endogenously in the brain.

AASs also may interact with enzymes involved in neurosteroid metabolism, thereby modulating the action of these neurosteroids, which are known to produce effects on various behaviors , Rats and mice display conditioned place preference to testosterone — , and male hamsters will self-administer testosterone to the point of death AASs enhance β-endorphin in the ventral tegmental area and may thereby activate the brain reward system.

Interestingly, the opioid antagonist naltrexone can block testosterone self-administration in hamsters These observations, combined with others, suggest that opioidergic mechanisms may be involved in the hedonic pathway to AAS dependence , Recent evidence suggests that supraphysiologic levels of testosterone and other AASs exhibit apoptotic effects in a variety of cell types , — , including human neuronal cells Two subsequent studies have now also demonstrated neurotoxic effects of supraphysiologic AAS in mammalian neuronal cells , A recent animal study found spatial memory deficits, as assessed by the Morris water maze, in rats after supraphysiologic AAS exposure Collectively, these findings raise the ominous possibility that long-term users of high-dose AAS might develop potentially irreversible cognitive deficits , In a pilot study exploring this possibility among 31 AAS user and 13 nonuser weightlifters, one group of investigators found significant deficits in visuospatial memory among AAS users as opposed to nonusers; and within the AAS-users group, these deficits were significantly associated with a total lifetime burden of AAS exposure Thus, the possibility of AAS-induced neurotoxicity clearly demands further study.

As mentioned above, AASs suppress HPT function , When individuals stop taking AASs after a lengthy course of use ie, several months or longer , HPT activity may be suppressed for months , or years , ; and some individuals may never regain normal testosterone levels.

Furthermore, AAS may also produce direct toxic effects on the testis , which may be irreversible, so that some AAS users will continue to display primary hypogonadism even after hypothalamic and pituitary functions have returned to normal However, case reports also have described failure with these interventions , To date, we are not aware of any systematic treatment studies in AAS-induced hypogonadism.

The suppression of pituitary LH and FSH secretion by AAS can be associated with suppression of spermatogenesis and infertility in men and menstrual irregularity and infertility in women. In addition to the direct adverse effects of AAS, illicit users are vulnerable to infectious complications associated with use of contaminated needles, contaminated products obtained on the black market, or other risks associated with weightlifting and AAS use.

Moreover, respondents to Internet surveys are likely better educated and more affluent than the population of AAS users as a whole 39 , 87 , so that Internet surveys likely underestimate the prevalence of unsafe practices in the global population of AAS users.

Thus, it is not surprising that the literature has documented various infectious complications of AAS use, including the blood-borne pathogens, HIV, hepatitis B, and hepatitis C, as well as skin and soft tissue infections, most notably due to community-acquired methicillin-resistant Staphylococcus aureus MRSA.

The first report of HIV infection in an AAS user surfaced nearly 30 years ago , and subsequent reports in both the United States and Europe have documented additional cases. AAS users have also contracted hepatitis B and C 92 , The greatest risk for transmission of HIV and other diseases in AAS users appears to arise from needle sharing and other unsafe needle practices 90 , This is likely because of the frequent use of injectable preparations, such as testosterone and nandrolone, among long-term illicit AAS users.

However, unsafe needle practices represent only one possible risk factor for HIV and other infections in AAS users. For example, a study of homosexual men in London gyms found that current AAS users were significantly more likely than never-users to report unprotected anal intercourse with partners of unknown serostatus, even in analyses adjusting for potential confounders Given that AASs are widely used by homosexual men, both illicitly 93 and as prescribed treatments for the wasting syndrome associated with HIV infection , there is a clear opportunity for the spread of HIV both through needles and sexual practices.

AAS users are also likely to have spent time in prison 1 , , , , , , and prisoners, in turn, are well-documented to display an elevated risk for hepatitis and HIV — Studies have linked community-acquired MRSA colonization and soft tissue infection with competitive sports participants Additional research has linked injection of drugs with community-acquired MRSA infection Studies have also reported soft tissue abscesses related to anabolic-steroid injections , AAS use is associated with dose-related increases in hemoglobin and hematocrit, and polycythemia is a frequent adverse event of AAS use , — Androgens stimulate erythropoiesis by increasing sensitivity to erythropoietin, suppressing hepcidin transcription, and increasing iron availability for erythropoiesis — Muscular AAS users engaged in heavy weightlifting can display rhabdomyolysis , sometimes with massive elevations of serum creatine kinase levels — , leading to myoglobinemia, myoglobinuria, elevated creatinine levels, decreased glomerular filtration rate , and the occasional progression to acute renal failure 51 , Notably, one recent case series has documented 10 cases of focal segmental glomerulonephritis among frequent AAS users AASs may occasionally cause hepatotoxicity, with consequences including peliosis hepatis an accumulation of blood-filled cysts in the liver — , and various types of hepatic tumors — Virtually all AAS-associated hepatotoxic effects are associated with orally active 17α-alkylated AASs , — The frequency of AAS-induced hepatotoxicity is likely overestimated, however, because rhabdomyolysis from heavy workouts can increase transaminases , , and this finding may be erroneously interpreted as evidence of abnormal liver function AASs may cause adverse musculoskeletal effects , , especially tendon rupture — , attributable both to the disproportionate strength of hypertrophied muscles and to possible deleterious effects of AAS on the architecture of the tendons themselves — AASs may affect the immune system , the lungs , and possibly other organ systems 18 and might cause acne , although knowledge in these areas remains limited.

Notably, there is little evidence of an association between AAS use and cancer, with the exception of rare reports of hepatic cancers , intratesticular leiomyosarcoma , and renal cell carcinoma , Conspicuous by their absence are reports of prostate cancer in AAS users.

To date, there is no clear evidence that androgen administration causes prostate cancer; we are aware of only 2 case reports of prostate cancer in bodybuilders, both published more than 20 years ago , However, the possibility remains that high doses of AAS administered during the peripubertal period may exert long-term epigenetic effects and may increase the risk of prostate-related events later in life.

Given that older AAS users who started AAS use in their peripubertal years in the s are just now entering the fifth decade of their life, we may have more evidence regarding AAS use and prostate cancer in the coming years.

Given the mounting evidence of adverse effects related to PED use, there is strong justification for the need to improve methods for detecting illicit PED use and eliminating abuse by both athletes and nonathletes, despite occasional arguments by some authors that PEDs be explicitly allowed in athletic competitions — Some of the adverse effects seen in patients who use AASs may include infertility, gynecomastia, sexual dysfunction, hair loss, acne, muscular appearance, and testicular atrophy.

Some indicators that might suggest AAS use are increased hemoglobin and hematocrit; suppressed LH, FSH, and testosterone levels; low high-density lipoprotein cholesterol, and low sperm density.

Mass spectrometry-based tests available in many commercial laboratories can detect AASs in urine. Testosterone abuse is more difficult to detect, but high testosterone, in association with suppressed LH and FSH levels, should raise suspicion of testosterone abuse.

Often direct questioning will result in an admission by a patient that he or she is using AASs. In , Donike and coworkers first reported a method for detecting testosterone abuse. They based their method on the fact that exogenously administered testosterone is predominantly excreted in the urine as the glucuronide conjugate.

WADA has decreased the ratio consistent with doping to Because of the high frequency of this polymorphism among East Asian populations, the likelihood of a false-negative test is higher in these populations than in Caucasian populations. The CIRs for androsterone, etiocholanolone, 5α- and 5β-androstanediol, and testosterone are documented.

As an internal reference, tests use an endogenous steroid either upstream of the steroid of interest or from another steroid pathway, such as pregnanediol. The use of the CIR in conjunction with the steroid profile results can provide a definitive answer about whether the athlete used a pharmaceutical testosterone product or not.

Use of either magnetic sector or orbitrap mass spectrometers in the high mass resolution mode significantly decreased limits of detection and lengthened the detection window Human GH is a metabolic hormone in adults with fused epiphyses of the long bones.

Those with hGH deficiency experience a loss of its anabolic and lipolytic activities, which is characterized by decreased lean body mass and increased fat mass with abdominal obesity, loss of bone mineral density, diminution of muscle strength and aerobic capacity maximal oxygen uptake [VO 2max ] , and reduced physical performance and quality of life, usually noted as diminished well-being.

Most of these findings of hGH deficiency are reversed by recombinant hGH rhGH replacement, although restoration may take months to a few years and might not be complete In addition to rhGH, GH-releasing peptides, ghrelin mimetics, and other growth factors are now available on the Internet, although we do not have data on the prevalence of their use.

The GH gene cluster on chromosome 17q The pituitary GH-secreting cells express the GH-N gene, whereas the placenta expresses GH-V and chorionic somatomammotropin genes The rhGH produced for therapeutic purpose is a —amino-acid, 22 molecular weight, single-chain polypeptide, which is similar to the product of the native GH-N gene, which makes detection of GH doping challenging , The predominant circulating form of GH secreted by the pituitary is the 22K form often referred to as the 22K-GH Alternate splicing of the GH-N gene yields another GH isoform, the 20K-GH variant, whose structure is similar to that of the 22K-GH except for the deletion of the residues 32 to Additionally, studies have described several posttranslationally modified monomeric GH isoforms and oligomeric series of at least up to pentameric GH , Thus, in healthy adults, circulating endogenously produced GH exists in multiple isoforms, including 22K, 20K, and other oligomeric and acidic GH isoforms; this heterogeneity of isoforms distinguishes endogenous GH production from exogenously derived GH, which yields only a single 22K isoform , In GH-deficient adults, replacement therapy with rhGH improves fat and protein metabolism, leading to a partial reversal of these abnormalities but not complete restoration to normal The metabolic actions of hGH also interact with those of insulin and perhaps IGF-1 to control fat.

hGH enhances lipolysis and fatty acid oxidation as well as carbohydrate and protein metabolism during both the fasted and fed states.

In the fasted state, GH secretion increases and it partitions metabolic fuels from fat by stimulating lipolysis and fatty acid oxidation to provide energy to protect from catabolism. At the whole-body level, GH suppresses glucose oxidation and utilization while at the same time enhancing hepatic glucose oxidation.

GH also antagonizes insulin action, promotes protein anabolism and the acquisition of lean body mass, and reduces urea synthesis, blood urea concentration, and urinary urea excretion. In adults with GH deficiency, rhGH replacement restores muscle strength toward normal over several years, but even after 3 years, the muscle strength in these persons is well below that of healthy controls.

Impaired exercise capacity in GH-deficient individuals, as measured by the VO 2max method, increased virtually to the level in healthy controls after rhGH replacement. In healthy adults, hGH regulates all of the activities mentioned above protein anabolic effects , spares protein oxidation, increases lean body mass extracellular water and body cell mass , and decreases fat mass Despite these changes in body composition, there is little evidence that hGH in supraphysiologic doses affects physical performance , , A systematic review of randomized trials concluded that although GH increases lean body mass, it may not improve strength The systematic review seemed to indicate that hGH may in fact decrease exercise capacity and may be associated with adverse events Birzniece and colleagues summarized the data, noting that the scientific literature does not support claims that hGH administration enhances physical performance, but there is some evidence regarding the effects of hGH on some athletic performance outcomes, such as anaerobic capacity.

Only a few studies have shown positive effects on athletic performance — The first was a study of abstinent anabolic steroid-dependent competitive athletes who were likely in a mild catabolic state The second was a study of recreational athletes who received a combination of a modest dose of rhGH and moderately supraphysiologic doses of testosterone in a controlled trial This study showed that rhGH administration was associated with improvement in sprint capacity in those receiving the combination of drugs, but the increases in sprint capacity were not sustained 6 weeks after discontinuation of the drug Although results might show only a small decrease in time to complete the sprint event, these seemingly minor differences may be crucial in elite athletic competitions.

The anabolic effects observed with the doses of rhGH use in randomized trials may not fully reflect those that might be associated with the massive doses and combinations used in the real world. Furthermore, PED users typically take cocktails of PEDs often in high doses, and thus few statements can be made implicating the effect of one or another pure agent, especially at low doses.

However, the lack of experimental evidence does not necessarily diminish the allure of hGH for athletes. The expectation that suprasphysiologic levels of hGH or IGF-1 might increase an individual's athletic performance is enough to encourage use.

Even if the administration of rhGH does not increase athletic performance, some elite athletes may take it to purportedly recover more rapidly eg, from soft tissue damage and allow for more vigorous training.

There are no systematic studies of the adverse effects of GH use. Therefore, most of the information is anecdotal, and these reports are often confounded by concurrent use of other PEDs, especially AASs. The likely adverse effects include edema, excessive sweating, myalgias and arthralgias, carpal tunnel syndrome, and diabetes Table 2.

Much of the information about potential adverse effects of rhGH use in supraphysiologic doses has been inferred from the studies of patients with acromegaly, a disease of excessive GH production with elevated GH levels at all times usually for many years.

GH excess in patients with acromegaly is characterized by acral enlargement, excessive sweating, hypertension, congestive heart failure, cardiomyopathy, sleep apnea, arthropathy, carpal tunnel syndrome, increased insulin resistance, neuropathy, diabetes, and increased mortality Retrospective analyses of patients with acromegaly have suggested increased frequency of benign and malignant neoplasms — Thyroid nodules and cancers, colonic polyps and cancers, and endometrial and cervical cancers are the most frequently reported neoplasms in patients with acromegaly — Adverse Events Associated With rhGH Use a.

Two tests have been developed for the detection of rhGH: a direct method that measures variants of GH produced by the pituitary gland and a biomarkers method based on the GH-induced release of IGF-1 and the N-terminal propeptide of procollagen type III P-III-NP , In the variants or isoforms test, one immunoassay detects primarily pituitary isoforms of GH including the kDa isoform, oligomers of the kDa isoform, and some other isoforms.

The second immunoassay primarily detects the monomeric kDa GH found in rhGH preparations. When a subject receives GH, it increases the concentration measured by the second assay and suppresses the pituitary forms, decreasing the concentration. The main limitation of any direct GH test is the short serum half-life of GH, which limits the detection window to less than 24 hours.

The biomarkers test is based on a score calculated from the age of the athlete, the IGF-1 concentration, and the P-III-NP concentration By combining the 2 tests, one can correctly classify subjects who had received GH from normal subjects for a period of at least 7 to 10 days.

We can measure the concentration of IGF-1 by immunoassay and, more recently, by liquid chromatography tandem mass spectrometry. The P-III-NP is measured by immunoassay and can stay elevated for several weeks even after discontinuation of rhGH use Insulin is purportedly a PED, but most information on illicit insulin use is anecdotal.

Athletes and nonathletes often use it after heavy workouts to enhance recovery. It is popular because it is cheap and available.

The ingestion of glucose is vital to this type of doping, given the glucose-lowering action of insulin, especially in those with normal tissue insulin sensitivity. The rationale of injecting insulin as a PED relates to its mediation of increases in the transport of glucose and amino acids into skeletal muscle and its effects on muscle fibers.

They also reported a decrease in the concentrations of the essential amino acids, implicating incorporation into the muscle fiber. There was little effect on protein breakdown. The investigators concluded that insulin promoted muscle anabolism primarily by stimulating protein synthesis independently of any effect on the transmembrane transport of glucose or amino acids.

Insulin use also accelerates lipogenesis, inhibiting the release of free fatty acids a muscle fuel ; this is especially significant for endurance athletes. However, athletes can gain additional weight adipose tissue as well , which could be detrimental to performance in many sports, especially those separated into weight classes.

Erythropoietin is a glycoprotein hormone that regulates red cell production. It is produced by the peritubular interstitial fibroblasts of the kidney and the perisinusoidal cells in the liver. In adults, the kidneys are the dominant source of circulating erythropoietin, although the liver is an important contributor to erythropoietin production in the fetal and perinatal period.

Erythropoietin stimulates erythropoiesis by binding to specific receptors on the surface of red cell progenitors, activating the Janus kinase 2 signaling pathway, and promoting the survival of these progenitors.

Erythropoietin receptors are expressed maximally on colony-forming units erythroid [CFU-E] cells and regulate further differentiation of these cells.

The burst-forming units erythroid [BFU-E] , proerthyroblasts, and basophilic erythroblasts also express erythropoietin receptors.

In addition to its effects on erythropoiesis, erythropoietin also plays a role in wound healing, angiogenesis, and the brain's response to hypoxic injury. Recombinant erythropoietins are effective in treating anemia associated with chronic kidney disease, myelodysplasia, cancer, and chemotherapy.

ESAs include the recombinant erythropoietins and other agents that stimulate erythropoiesis. ESA use is most prevalent in endurance sports, such as distance running, cycling, race-walking, cross-country skiing, biathlons, and triathlons ESAs increase net oxygen delivery to the muscle by increasing red cell mass VO 2max and thereby improving endurance.

ESA use in cycling started around and became widespread by A number of elite cyclists in the Tour de France, including Floyd Landis and Lance Armstrong, have admitted to using PEDs including erythropoietin.

A number of antidoping activists, Greg LeMond, Sandro Donati, etc, have documented the widespread use of ESAs in professional cycling.

Erythropoietins increase red cell mass and plasma viscosity and thereby augment the risk of thrombosis, cardiovascular events, and stroke Table 3.

Although there has been considerable media speculation that erythropoietin could have been implicated in the deaths of as many as 18 European professional bicycle racers between and , there is no forensic documentation from verifiable sources substantiating this claim , Meta-analyses of randomized trials in patients with cancer and in those with end-stage renal disease have revealed an increased risk of mortality, thromboembolic events, cardiovascular events including myocardial infarction and stroke , and hypertension.

Since the Olympics, WADA has used a combination of biochemical and hematologic tests to detect recombinant erythropoietin. The biochemical tests on urine are based on the differences in the electrophoretic mobility of recombinant erythropoietin and endogenous human erythropoietin, reflecting differences in glycosylation patterns and the isoelectric point.

An isoelectric focusing method separates the isoforms of erythropoietin, which are detected using double immunoblotting chemiluminiscence , The isoelectric point for each erythropoietin glycoform is determined by the presence of charged groups on the carbohydrate moieties.

The carbohydrate of recombinant erythropoietin, expressed from Chinese hamster ovary or baby hamster kidney cells, is different from that expressed in human kidney cells Reichel et al has reported a n SDS-PAGE method for detecting erythropoietin that also uses double immunoblotting chemiluminiscence.

The method separates the erythropoietin glycoforms on the basis of their hydrodynamic volume. Chemiluminiscence produces a single broad band; the position of the band is relatively sensitive to the carbohydrate content of the erythropoietin Recent studies have reported that a membrane-assisted isoform immunoassay test has excellent sensitivity , Because this test is performed on a membrane support, we can use either antibodies or lectins that separate various glycoforms in conjunction with the immune detection to assess whether the erythropoietin is native or recombinant.

However, the test may be negative if the sample is collected after 3 or 4 days of erythropoietin use, especially after administration of low doses. New models that also incorporate the measurement of hemoglobin, erythropoietin levels, and soluble transferrin receptor levels provide greater sensitivity, especially in users who may have taken small or moderate doses of recombinant erythropoietin several days or weeks before the test.

Direct detection of blood transfusions and ESAs erythropoietin, novel erythropoiesis stimulating protein darbepoetin alpha, and continuous erythropoietin receptor activator is often difficult.

Therefore, there's a growing trend toward monitoring biomarkers of erythropoiesis hemoglobin, hematocrit, and reticulocytes over time for an individual athlete and analyzing these data using analytical models to identify patterns suggestive of doping This type of monitoring is referred to as the Athlete Biological Passport.

With this information, athletes can either be sanctioned directly based on their profile or targeted with conventional doping tests. Both the International Cycling Union and other federations that have implemented the Passport to target athletes for the presence of ESAs have reported a reduction of blood doping among their athletes Studies are also exploring the excretion of plasticizers as indicators of autologous blood transfusion , PEDs have potential not only for direct medical consequences but also for exacerbating other conditions.

As previously stated, PEDs, especially when used in combination with other analgesics such as opiates and nonsteroidal anti-inflammatory drugs, may allow the athletes to engage in extremely intensive training exercises even in the face of previous injury, thus greatly increasing the risk of musculoskeletal injury.

Another concern relates to the possible interaction of AASs with CNS injuries, including traumatic brain injury and posttraumatic stress disorder. In recent years, clinical, scientific, and public attention has focused on the chronic neurologic and behavioral effects of head injuries in football players and soldiers These may represent the accumulated effects of repeated mild head trauma in football players or the lasting response to blast exposure in soldiers.

Unfortunately, we lack substantial clinical or basic science evidence to address this issue. Although the armed forces monitor blast injuries, they do not routinely test troops for AAS use Conversely, sports federations may test players for AAS but lack comparable data on concussive injuries.

Basic science has also largely overlooked the potential interaction of AASs and traumatic brain injury. For many neurologic conditions, estrogen is neuroprotective in females This is particularly true for response to hypoxic-ischemic brain damage, as occurs with stroke.

Whether testosterone at physiologic levels reduces or exacerbates neuronal injury in males remains unresolved One emerging hypothesis is that endogenous androgens may be harmful during the acute phase of ischemic brain injury but can have beneficial effects during recovery.

Even so, it is unclear how this may translate to the elevated levels of androgens characteristic of AAS use. Under these circumstances, the cellular targets and mechanisms of action may be substantially different from the effects at normal physiologic levels.

Gene doping has not been detected in any sports event to date, although many experts have predicted that gene doping will become a reality in the near future , — Currently, it remains a theoretical but plausible threat in competitive sports, but because of its complexity and expense, gene doping is unlikely to be easily accessible to nonathlete weightlifters or to become a major public health problem in the near future.

The conceptual and technological framework of gene therapy in humans has largely been developed in hereditary diseases and some types of cancer , The methods used to deliver genetic material include the naked DNA, viral vectors, and genetically modified stem cells.

Viral vectors are the most frequently used approach for delivery of genetic material , — Applying antisense RNA sequences or inhibitory RNAs, blocking splicing recognition sequences, or using exon skipping can also modify gene expression.

The approved gene therapies include alipogene tiparvovec for the treatment of lipoprotein lipase deficiency and recombinant human adenovirus-p53 to inhibit cancer cell growth , Gene therapy has also shown promise in SCID-X1, Leber's congenital amaurosis, and some forms of muscular dystrophies.

Despite its enormous promise, the progress in the gene therapy field has lagged substantially behind the early expectations because of technological and safety issues. A number of genes have been considered as candidates for doping, including erythropoietin, IGF-1, hGH, follistatin, myostatin, androgen receptor, peroxisome proliferator-activated receptor-δ, α-actinin 3, cytosolic phosphoenolpyruvate carboxykinase, vascular endothelial growth factor, fibroblast growth factor, and endorphin and encephalin , , In early trials in rhesus macaques, gene therapy with the erythropoietin gene was associated with the development of severe polycythemia, hyperviscosity, and autoimmunity — Subsequent studies have reported long-term regulated expression of erythropoietin in mice and macaques — Transgenic mice with lifelong hyperexpression of IGF-1 exhibit larger muscle mass but have substantially shortened lifespan , Studies have explored a number of strategies to inhibit myostatin, including the expression of myostatin propeptide, which blocks myostatin action; the expression of follistatin, which inhibits the action of myostatin and other TGFβ family members; or the hyperexpression of a modified myostatin gene, which lacks a cleavage site in the myostatin protein, resulting in reduced production of active myostatin protein — In addition to the methodologic problems that have limited the success of gene therapy to date such as limited expression of the recombinant protein and gene silencing , many safety issues remain to be resolved , — These safety concerns include immune reactions to the vector proteins or to the recombinant protein itself; the viral vector integrating with host genome in an unpredictable manner; the viral vector integrating with tumor suppressor genes, which could increase the risk of cancers; the unregulated hyperexpression of the recombinant protein eg, IGF-1 , which could pose serious health problems, especially as users get older; and the genetic material transfecting the germ cells and transmitting to the offspring.

Currently, there are no WADA-approved methods for the detection of gene doping. However, researchers are developing novel technologies to detect gene doping based on structural differences in the transgene or differences in the posttranslational modifications of the recombinant proteins 40 , , The long-term adverse consequences of PED use remain inadequately studied Table 4.

Uncontrolled studies, retrospective reviews, and case reports indicate that PED use is associated with serious health consequences including the increased risk of death as well as the risk of cardiovascular, psychiatric, metabolic, endocrine, neurologic, infectious, hepatic, renal, and musculoskeletal disorders.

To date, no systematic prospective studies of the medical consequences of PED use exist. Widespread misperception that PEDs are safe or associated with manageable adverse effects has contributed to their growing use and to a substantial neglect of PED use as a serious public health problem.

Therefore, long-term observational studies to determine the health risks associated with PED use are a public health imperative. Randomized trials would be both unethical and inappropriate for studying the adverse health effects of PEDs, because such trials cannot be ethically designed with safety as a primary endpoint.

Furthermore, such hypothetical trials could not duplicate the highly supraphysiologic doses of PEDs or long durations of PED exposure experienced by illicit users, nor could such trials recreate the lifestyle factors and other high-risk behaviors associated with PED use.

Thus, an observational study design, implemented by establishing a registry, may not only provide better evidence than randomized trials but may be the only feasible method of collecting scientifically meaningful and valid outcome data for this form of illicit substance use.

There is an urgent need to establish such long-term prospective studies and registries. PED use appears to be far more prevalent than is generally believed and is widespread among nonathlete weightlifters. Therefore, epidemiologic surveys to determine the prevalence of PED use and the evolving patterns of PED use in the general adult population are an equally important priority.

The mechanisms by which PEDs exert their adverse health effects also remain unclear and need further investigation. Animal models may be particularly useful in studying the mechanistic pathways that contribute to the adverse effects of PEDs. An understanding of these mechanistic pathways may unveil targets for therapeutic intervention.

AAS withdrawal is another issue that needs further investigation. When AAS users stop taking steroids, they often experience distressing symptoms associated with a suppressed HPT axis.

There are no data from intervention trials of therapeutic modalities eg, estrogen receptor antagonists, aromatase inhibitors, and opiate antagonists to mitigate the AAS withdrawal syndrome and facilitate recovery of the HPT axis. Therefore, therapeutic trials to treat the AAS withdrawal syndrome are equally important.

We also need to further investigate the interactive effects of PEDs with sports injuries and other high-risk behaviors as well as innovative approaches to enhance public awareness of the serious health consequences of PEDs.

Dr Jag H. Khalsa, chief of the Medical Consequences Branch, National Institute on Drug Abuse NIDA , served as a member of the expert panel that was assembled by The Endocrine Society. Because Dr Khalsa is the program officer on a National Institutes of Health NIH grant held by one of the coauthors, he requested that his name be removed from the author list and added to the Acknowledgments, citing this conflict of interest by NIDA's policies.

The authors gratefully acknowledge the expert literature search assistance from medical librarians Andrea Horne Denton, MILS Master of Information and Library Science , Karen Knight, MSLS Master of Science and Library Science , and Kelly Near, MSN Master of Science in Nursing , WHNP-BC Women's Health Nurse Practitioner — Board Certified , MLS Master of Library Science from the University of Virginia Claude Moore Health Sciences Library.

The preparation of this Scientific Statement was supported entirely by the Endocrine Society. The following grants are also acknowledged from the National Institutes of Health NIH : 5RO1AG and 2UO1AG to S.

Disclosure Summary: The authors have no conflicts in relation to this research. has received research grants from the NIH, AbbVie, Regeneron, and Eli Lilly and Company for other research not directly related to this project. has received grant support from NIDA and testified in cases related to AAS use.

has received grant support from the Swedish Research Council and has provided expert testimony on the action of AASs in a Swedish court. is an employee of the United States Anti-Doping Agency. reports no conflict. The authors received no remuneration for their contributions to the preparation of the manuscript.

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It is in every sport. The tests are probably useful in skimming off the worst abuse, requiring juiced athletes to moderate their doses — a pretty valuable effect, if you think about this clearly. The tests may even scare off some potential users, but they won't clean up a sport.

Drug-related suspensions, performance enhancing or otherwise, have become commonplace throughout the past ten years. But what physical advantages make the risk of suspension so tempting to athletes? Simply put, many of the drugs athletes take illegally are designed to increase their athletic performance.

For example, steroids and related hormones such as testosterone are used to increase muscle mass and strength by promoting testosterone production. Steroids can also aid with recovery from workouts by reducing and helping heal the damage to muscles that occurs during workout sessions, enabling an athlete to work out harder and more often while minimizing the risk of overtraining.

Marijuana provides an interesting case for the leagues. The leagues tend to treat marijuana as a recreational drug; athletes, however, have cited it as a substance that helps with recovery and pain management. However, steroids and its related hormones have visible side effects, especially when taken at higher than medically safe doses.

Men may experience prominent breasts, baldness, shrunken testicles, infertility, and impotence, as well as acne, an increased risk of tendinitis, liver abnormalities, high blood pressure, aggressive behaviors, psychiatric disorders, and more.

To combat these side effects of anabolic steroid use, many athletes turn to anti-estrogens , which mask many of the telltale signs of steroid use. Adderall is typically prescribed for ADHD and other related conditions as a way to help the patient focus, remain calm, and maintain concentration.

However, studies have shown that Adderall and related drugs can help improve hand-eye coordination, acceleration, and strength, which athletes could benefit from in addition to improved focus and concentration. While the goals of taking drugs — improving performance or recovery time — are largely the same across sports, the policies of major sports all vary considerably regarding their testing methods and penalties.

For the major sporting leagues in the United States, the drug policy is generally determined by the league and negotiated during collective bargaining the NCAA , interestingly, relies principally on the testing programs at their affiliated institutions, which vary widely; however, the NCAA typically makes several visits throughout the year to ensure policies are being upheld.

Prior to entering the league, only the NFL requires pre-employment testing for all players, although in the MLB, all players are subjected to testing within five days of reporting for spring training. The NBA, NHL, NCAA, and all other professional leagues do not require pre-employment testing.

The frequency with which players are tested also varies greatly among professional leagues. In the NFL, all players are tested at least once per year, and the policy allows for targeted testing. Ten players per team are randomly tested each week, which continues during the playoffs for teams in the postseason.

There may also be up to six offseason tests per player. In the NBA, all players are subject to four random tests per season, and the league conducts reasonable-cause testing. Similarly, in the NFL, players are tested up to three times per year at random.

Surprisingly, in the MLB, players are only subject to the test within five days of reporting for spring training and one other test on a randomly selected date, in addition to random tests in and out of season.

In the NFL, a first violation leads to a minimum four-game suspension, while a third violation calls for a minimum month suspension as well as disqualification from the Pro Bowl and other honors for the year.

In the NBA , the first positive result for PEDs earns a game suspension; the fourth violation results in disqualification from the league. If a first-year player tests positive for drugs of abuse, he earns a one year suspension with a chance of reinstatement after one year; all other players are suspended for at least two years.

A second violation leads to a game suspension without pay, and a third violation leads to a lifetime ban. However, violations of drugs of abuse are treated clinically first, rather than through suspension.

In the NFL, upon testing positive for a banned PED, the player is notified and the sample which is split in half during the original phase of testing is re-tested. Mandatory physical examinations are conducted to rule out naturally occurring high levels of chemicals such as testosterone , and psychological examinations may also be conducted in case of suspected addition.

The burden of proof is placed on the league during an appeals process. In the NBA, meanwhile, the approach is much more recovery-focused. Players who come forward with their drug problems receive league-funded counseling from the Life Extension Institute , a hour counseling center funded jointly by the NBA and the NBPA.

Mayo Clinic offers Recovery meal options in Performance-enhancign, Florida and Minnesota and Peppermint candy recipe Mayo Clinic Performance-enhancong System Risk factors of performance-enhancing substances. Hoping to get an edge by taking performance-enhancing drugs? Learn how these drugs work and how they can have effects on your health. Most serious athletes feel a strong drive to win. They often dream big too. Performance-enhancing reduce belly bulge Risk factors of performance-enhancing substances, also known as performance-enhancing drugs Subetances[1] are performacne-enhancing that are used to improve Overcoming anxiety challenges form of activity performance substancees humans. Risk factors of performance-enhancing substances well-known performance-enhancinh of cheating in sports involves doping in sportwhere banned physical performance-enhancing drugs are used by athletes and bodybuilders. Athletic performance-enhancing substances are sometimes referred as ergogenic aids. Performance-enhancing substances are also used by military personnel to enhance combat performance. The use of performance-enhancing drugs spans the categories of legitimate use and substance abuse. The classifications of substances as performance-enhancing substances are not entirely clear-cut and objective.


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