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Introduction, implications of studies of humans for studies of nonhuman animals, conclusions, acknowledgments.

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Steroid use and human performance: Lessons for integrative biologists

From the symposium “Hormonal Regulation of Whole-Animal Performance: Implications for Selection” presented at the annual meeting of the Society for Integrative and Comparative Biology, January 3–7, 2009, at Boston, Massachusetts.

2 Present address: Department of Biology, University of South Dakota, Vermillion, SD 57069, USA

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Jerry F. Husak, Duncan J. Irschick, Steroid use and human performance: Lessons for integrative biologists, Integrative and Comparative Biology , Volume 49, Issue 4, October 2009, Pages 354–364, https://doi.org/10.1093/icb/icp015

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While recent studies have begun to address how hormones mediate whole-animal performance traits, the field conspicuously lags behind research conducted on humans. Recent studies of human steroid use have revealed that steroid use increases muscle cross-sectional area and mass, largely due to increases in protein synthesis, and muscle fiber hypertrophy attributable to an increased number of satellite cells and myonuclei per unit area. These biochemical and cellular effects on skeletal muscle morphology translate into increased power and work during weight-lifting and enhanced performance in burst, sprinting activities. However, there are no unequivocal data that human steroid use enhances endurance performance or muscle fatigability or recovery. The effects of steroids on human morphology and performance are in general consistent with results found for nonhuman animals, though there are notable discrepancies. However, some of the discrepancies may be due to a paucity of comparative data on how testosterone affects muscle physiology and subsequent performance across different regions of the body and across vertebrate taxa. Therefore, we advocate more research on the basic relationships among hormones, morphology, and performance. Based on results from human studies, we recommend that integrative biologists interested in studying hormone regulation of performance should take into account training, timing of administration, and dosage administered when designing experiments or field studies. We also argue that more information is needed on the long-term effects of hormone manipulation on performance and fitness.

One of the most widely discussed and controversial arenas of human performance concerns the use of steroid supplements to enhance athletic ability for a variety of sports, ranging from bicycling to baseball. There is strong evidence that human athletes have attempted to enhance their athletic performance using steroids since the 1950s, but whether, and in which sports, steroids are actually effective remains controversial (reviewed by Ryan 1981 ; George 2003 ; Hartgens and Kuipers 2004 ). In general, steroids used by athletes encompass a wide variety of forms of the androgen testosterone (George 2003 ), and most seem to have the classical androgenic and anabolic effects on men, although steroid use by women cannot be ignored (Malarkey et al. 1991 ; Gruber and Pope 2000 ). Alternative forms of testosterone (e.g., testosterone enanthate, methandrostenolone) are typically used by those desiring enhanced performance because ingested or injected testosterone is quickly metabolized into inactive forms (Wilson 1988 ). Thus, studies of humans that we cite involve testosterone derivatives. Early studies of the effects of steroids on human performance, however, had major flaws in design, such as lack of control groups and a double-blind procedure, the presence of confounding factors (e.g., differences in level of exercise and in motivation), and inappropriate statistical techniques (reviewed by Bhasin et al. 2001 ; George 2003 ). These problems left open for many years the question of whether, and in what capacity, steroids actually enhance athletic performance, until more recent studies conclusively showed significant effects of steroids.

The topic of steroid effects on human athletic performance is germane to an emerging field of research investigating hormonal effects on animals’ performance (e.g., sprint speed, endurance capacity, bite-force capacity) (Husak et al. 2009a ), as testosterone may exert general effects on performance across widely divergent vertebrate taxa. Our goal in this review is to interpret the effects of steroids on human performance in this broader context of hormonal effects across a wider range of taxa. We are particularly interested in drawing lessons and potential avenues of research for animal biologists from published research on humans. We have performed a selective review of studies examining how humans' use of steroids affects skeletal muscle physiology and subsequent athletic performance. While studies of performance on nonhumans have dealt extensively with the effects of morphological traits on performance and the impact of performance on individual fitness (Arnold 1983 ; Garland and Losos 1994 ; Irschick and Garland 2001 ; Irschick et al. 2007 , 2008 ; Husak et al. 2009a ), there has been relatively little synthetic discussion of how hormones affect performance in non-human animals. We also point the reader towards several recent reviews of steroid use and performance by humans for details not discussed in our review (Bhasin et al. 2001 ; George 2003 ; Hartgens and Kuipers 2004 ).

General effects of testosterone on the phenotype of males

The development of primary and secondary sexual characteristics is stimulated by testosterone in vertebrate males, and these effects can be either organizational or activational in nature (Norris 1997 ; Hadley 2000 ). Organizational effects tend to occur early in development, and during a critical window of time, thereby resulting in permanent effects. On the other hand, activational effects occur in adults, and the effects are typically temporary (Arnold and Breedlove 1985 ). The hypothalamus stimulates production of gonadotropin-releasing hormone, which in turn stimulates production of luetenizing hormone in the anterior pituitary. Luetenizing hormone then stimulates production of testosterone in the Leydig cells of the testes. Testosterone then circulates throughout the body where it exerts effects on multiple target tissues that have the appropriate receptors or appropriate enzymes (e.g., aromatase or 5α-reductase) to convert testosterone for binding to other types of receptors (Kicman 2008 ). The widespread effects of circulating levels of testosterone on aggression, secondary sexual traits, and growth of skeletal muscle in males of many vertebrate species are well-documented (Marler and Moore 1988 ; Wingfield et al. 1990 ; Ketterson and Nolan 1999 ; Sinervo et al. 2000 ; Ketterson et al. 2001 ; Oliveira 2004 ; Adkins-Regan 2005 ; Hau 2007 ; contributions in this issue). In particular, production of testosterone by males has been linked with the expression of color and behavioral display signals, as well as aggression (Marler and Moore 1988 ; Kimball and Ligon 1999 ; Hews and Quinn 2003 ; Adkins-Regan 2005 ; Cox et al. 2008 ) and increased growth (Fennell and Scanes 1992 ; Borski et al. 1996 ; Cox and John-Alder 2005 ), although this latter effect may depend on specific selective pressures on males (Cox and John-Alder 2005 ).

Effects of testosterone on the physiology of human skeletal muscle

Testosterone has multiple effects on skeletal muscle at the biochemical and cellular levels, but the direct cause-and-effect relationships among these effects are still unclear (Sinha-Hikim 2002 ; Hartgens and Kuipers 2004 ). The studies that we discuss here, and throughout the paper are from experiments or correlative studies conducted on adult individuals such that the effects seen are activational in nature, causing rather rapid changes to the phenotype. Increased testosterone causes increased protein synthesis by muscle cells (Griggs et al. 1989 ; Kadi et al. 1999 ; Hartgens and Kuipers 2004 ), which is necessary for anabolic effects and an increase in lean muscle mass. Sinha-Hikim et al. ( 2002 ) found a dose-dependent increase in the mean number of myonuclei found in skeletal muscle fibers ( vastus lateralis muscle) with testosterone supplementation, as well as in the number of myonuclei per fiber (see also Eriksson et al. 2005 ). This increase was also associated with an increase in the number of satellite cells in the muscle tissue (but see Eriksson et al. 2005 ). Satellite cells are progenitor cells found external to muscle fibers that are incorporated into fibers and promote repair and growth of the muscle (Kadi and Thornell 2000 ; Reimann et al. 2000 ). However, the mechanism by which testosterone causes an increase in the number of satellite cells is unknown and could be due to testosterone (1) promoting cell division of satellite cells, (2) inhibiting apoptosis of satellite cells, or (3) causing differentiation of stem cells into satellite cells (Sinha-Hikim 2002 ). In any case, the functional implications for these findings are clear. More satellite cells likely result in more myonuclei per fiber, which, combined with increased protein synthesis, contribute to increases in muscle growth via an increased number and hypertrophy of muscle fibers (Kadi 2000 ; Kadi and Thornell 2000 ).

Testosterone also appears to cause a dose-dependent increase in the cross-sectional area of muscle fibers, although details about which types of fibers are affected and where in the body this occurs remains equivocal. Testosterone may increase the cross-sectional area of both type I (oxidative “slow twitch”) and type II (glycolytic “fast twitch”) fibers simultaneously after administration (Sinha-Hikim 2002 ; Eriksson et al. 2005 ), but other studies have shown greater increases in type I than in type II fibers (Hartgens et al. 1996 ; Kadi et al. 1999 ; also in growing rats, Ustunelet al. 2003 ), increased size in only type I fibers (Alén et al. 1984 ; Kuipers et al. 1991 , 1993 ), or increased size in only type II fibers (Hartgens et al. 2002 ). These mixed results are intriguing, because they suggest that different parts of the body, and, hence, different performance traits, may be affected differently by elevated testosterone levels. The likely mechanism for these differences is variation in density of receptors within the myonuclei of muscle fibers in different regions of the body (Kadi 2000 ; Kadi et al. 2000 ). An alternative hypothesis is that different types of fiber have differing relationships between the number of internal myonuclei and muscle cross-sectional area during hypertrophy (Bruusgaard et al. 2003 ). That is, some types of fibers may have internal myonuclei that can serve larger “nuclear domains” than can other types of fibers (reviewed by Gundersen and Bruusgaard 2008 ). If either of these hypothesized mechanisms is correct, then circulating levels of testosterone may only explain a portion of inter-individual (or interspecific) variation in performance. Testosterone may also stimulate changes in the proportions of types of fibers in muscles (Holmang et al. 1990 ; Pette and Staron 1997 ), although evidence for this effect in humans is mixed. For example, Sinha-Hikim et al. ( 2002 ) did not observe a change in the proportions of type I and type II fibers after administration of testosterone.

Changes in lower-level traits (e.g., protein synthesis, number of satellite cells, cross sectional area of muscle fibers) after testosterone supplementation, as described above, thus, result in changes at the whole-muscle level and explain many of the classic effects of testosterone that are desired by humans using steroids. That is, increasing testosterone via steroid use increases body weight, lean body mass, as well as cross-sectional area, circumference, and mass of individual muscles (i.e., “body dimensions”); however, there are numerous studies with contradictory results, finding no change in one, or all, of these traits, depending on the drug used, the dose taken, and the duration of use (reviewed by Bhasin et al. 2001 ; Hartgens and Kuipers 2004 ). The finding that testosterone can change muscle physiology and increase whole-muscle size and/or body mass is consistent with results in nonhuman animals. For example, testosterone implants increased size and number of fibers in the sonic muscles of male plainfin midshipman fish ( Porichthys notatus ) (Brantley et al. 1993 ). Similarly, testosterone supplementation increased muscle mass and changed contractile properties of trunk muscles of male grey treefrogs ( Hyla chrysoscelis ) (Girgenrath and Marsh 2003) and of forelimb muscles of male frogs ( Xenopus laevis , Regnier and Herrera 1993 ; Rana pipiens , Sidor and Blackburn 1998 ).

Effects of testosterone on humans’ performance

Whether steroids actually enhance performance of athletes was a subject of great controversy throughout the 1980s and 1990s (Ryan 1981 ; Haupt and Rovere 1984 ; Cowart 1987 ; Wilson 1988 ; Elashoff et al. 1991 ; Strauss and Yesalis 1991 ; Hartgens and Kuipers 2004 ), largely due to flaws in design of early studies (see above). However, the past decade has seen a surge in more carefully designed studies that have convincingly tested whether, all else equal, steroids increase performance. Hartgens and Kuipers ( 2004 ) found that 21 out of 29 studies they reviewed found an increase in humans’ strength after steroid use, with improvements in strength ranging from 5% to 20%. Storer et al. ( 2003 ) found that testosterone caused a dose-dependent increase in maximal voluntary strength of the leg (i.e., amount of weight lifted in a leg press), as well as in leg power (i.e., the rate of force generation). They further tested whether increased muscle strength was due simply to increased muscle mass or to changes in the contractile quality of muscle affected by testosterone, but they found no change in specific tension, or in the amount of force generated per unit volume of muscle. This latter result suggests that, at least for leg-press performance, testosterone increases strength by increasing muscle mass and not by changing contractile properties. Rogerson et al. ( 2007 ) found that supraphysiological doses of testosterone increased maximal voluntary strength during bench presses (see also Giorgi et al. 1999 ) and increased output of work and output of power during cycle sprinting compared to placebo control subjects. Thus, “burst” or “sprint” performance traits appear to be enhanced by increased testosterone, and this is in general agreement with studies of nonhuman animals (John-Alder et al. 1996 , 1997 ; Klukowski et al. 1998 ; Husak et al. 2007 ). For example, experimentally elevated levels of testosterone caused increased sprint speed, relative to sham-implanted individuals, in northern fence lizards ( Sceloporus undulatus ) (Klukowski et al. 1998 ). These findings contrast with results for endurance events, in which no increase in performance has been detected experimentally in humans (reviewed in George 2003 ; Hartgens and Kuipers 2004 ). The finding that endurance by humans is not enhanced by testosterone is unexpected since testosterone may increase hemoglobin concentrations and hematocrit (Alén 1985 , but see Hartgens and Kuipers 2004 ) and exogenous testosterone increases endurance in rats (Tamaki et al. 2001 ) and male side-blotched lizards ( Uta stansburiana ) (Sinervo et al. 2000 ). More studies of the effects of increased testosterone on endurance would help to better clarify these seemingly paradoxical findings. One possibility that might explain species’ differences in endurance is the relative proportion of type I fibers available for enhancement, which likely varies across species (Bonine et al. 2005 ), although this hypothesis needs explicit testing. Steroid use does not seem to consistently enhance recovery time after strenuous exercise (reviewed in Hartgens and Kuipers 2004 ), although it may in non-human animals (Tamaki et al. 2001 ). Storer et al. ( 2003 ) also found no change in fatigability (i.e., the ability of a muscle to persist in performing a task) of muscle during exercise, which is consistent with other studies (George 2003 ).

One of the problems in early studies of steroid effects was that the participants’ history of training and exercise while taking steroids was not taken into account or controlled (Bhasin et al. 2001 ; George 2003 ; Hartgens and Kuipers 2004 ). Recent studies have shown that the presence or absence of exercise training during testosterone supplementation can have a marked impact on how much performance is enhanced, thus complicating results when training is not controlled. Bhasin et al. ( 2001 ) reviewed several examples of such results. They pointed out that testosterone supplementation alone may increase strength from baseline levels, but so will exercise alone with a placebo, such that strength levels with exercise alone are comparable to those with testosterone addition alone (Bhasin et al. 1996 ). Testosterone supplementation while undergoing exercise training typically has the greatest increase in strength compared to exercise only or testosterone only (Bhasin et al. 1996 , 2001 ). These findings are consistent with those of others (reviewed by George 2003 ). Indeed, George ( 2003 ) suggested that steroids will only consistently enhance strength if three conditions are met: (1) steroids are given to individuals who have been training and who continue to train while taking steroids, (2) the experimental subjects have a high protein diet throughout the experiment, and (3) changes in performance are measured by the technique with which the individuals were training while taking steroids. That is, one may, or may not, find a change in bench-press performance if individuals trained with leg presses, and not bench presses, while taking steroids. We note that the confounding effect of training is a rather intuitive finding, but it does point out potential problems in studies of non-human animals, specifically laboratory studies, which we address below.

Given the effects of steroids on physiology and performance of human muscle, what can integrative biologists take away from these findings? We suggest that they can provide some valuable insights into the mechanisms of how hormones might regulate whole-animal performance traits in nonhuman animals. The most obvious lesson is that manipulating the circulating levels of testosterone, or its derivatives, increases overall strength, which has apparent benefits for performance in bursts, such as sprint speed. In contrast, there is little evidence from studies on humans for a positive effect on capacity for endurance, which is counter-intuitive, given the known effect of testosterone on hemoglobin concentrations and hematocrit. However, these same studies of humans also raise a host of issues that merit special consideration by researchers interested in hormonal effects on nonhuman animals, including effect of training, timing of administration, and dosage administered. We also argue that more information is needed on the long-term effects of hormonal manipulation on performance and fitness. Although recent studies suggest that increasing testosterone levels can enhance certain types of performance, we are not advocating or justifying the use of steroids by humans. There are numerous side effects of prolonged steroid use in humans, including cardiovascular problems, impaired reproductive function, altered behavior, increased risk of certain tumors and cancers, and decreased immune function, among others (reviewed by Pärssinen and Seppälä 2002 ; George 2003 ). These “side-effects” are in accordance with studies of nonhuman animals where higher testosterone levels are associated with such detrimental effects as increased loads of parasites, reduced immunocompetence, decreased body condition, reduced growth, and increased use of energy, ultimately resulting in reduced survival (Marler and Moore 1988 ; Folstad and Karter 1992 ; Salvador et al. 1996 ; Wikelski et al. 1999 , 2004 ; Moore et al. 2000 ; Peters 2000 ; Klukowski and Nelson 2001 ; Wingfield et al. 2001 ; Hau et al. 2004 ). Indeed, it is the presence of these very “side-effects” that has driven a great deal of research on behavioral and life-history tradeoffs mediated by testosterone (Ketterson and Nolan 1999 ; Ketterson et al. 2001 ). Higher levels of testosterone may enhance performance and increase success at some tasks, but its widespread “pleiotropic” effects on other aspects of the phenotype may result in a net detriment to fitness (Raouf et al. 1997 ; Reed et al. 2006 ; Ketterson et al. 2009).

We encourage researchers to complete more detailed studies of the interactions among hormones, morphology, and performance, especially across different types of performance traits (dynamic versus regulatory, see Husak et al. 2009a ). Comparative data on whether the same, or different, hormones affect the same performance traits in different taxa (e.g., burst speed in fish, sprint speed in lizards) would be useful for understanding how different species have evolved unique, or conserved, endocrine control of morphology and function. A comparative approach is important, as other studies have shown different effects of testosterone on performance in different taxa (e.g., an increase in endurance for rats and lizards, but none for humans), and more research is needed to determine whether such differences are valid or purely methodological. Even though testosterone is confined to vertebrates, it is possible that studies with invertebrates may reveal similar effects on performance via different hormones, e.g., recent work showing a seemingly similar role of juvenile hormone for invertebrates as testosterone has for vertebrates (Contreras-Garduno et al. 2009 ; see also Zera 2006 ; Zera et al. 2007 ; Lorenz and Gäde 2009).

Correlative studies relating endogenous circulating hormone levels to natural variation in performance traits can provide valuable insight into potential mechanistic regulators of performance, but manipulations allow a more detailed examination of cause-and-effect relationships. Whether performance can be manipulated by reduction (castration) or supplementation (implants) of testosterone in nonhuman animals will depend on the type of performance and how it is affected by circulating levels of the androgen. Many dynamic performance traits, especially maximal performance, may show different responses to exogenous hormone in the laboratory versus field, compared to coloration or “behavioral” traits. For example, supplementation with testosterone may rapidly increase display behavior or aggression in the laboratory (Lovern et al. 2001 ; Hews and Quinn 2003 ) compared to control animals, or corticosterone supplementation may decrease sexually selected color patterns (reviewed by Husak and Moore 2008 ). These examples are in contrast to supplementing testosterone in the laboratory and testing for an effect on performance. Aggression and coloration will not likely require training of the target trait to reveal an observed effect, whereas some performance traits may require training. Furthermore, regulatory performance traits (e.g., regulation of ions in seawater), on the other hand, may respond more directly to hormonal manipulation (see McCormick 2009), and will likely not require any training, but more empirical data are necessary to make generalizations.

It is also important to more closely inspect those traits that show no significant effect of testosterone on dynamic performance after manipulation in the laboratory. Such a “noneffect” may be due to numerous possibilities, the most obvious of which is that testosterone simply has no effect on a particular type of performance. However, a second possibility is that muscles involved in performance were not adequately trained during administration of supplemental testosterone, or there was no control of exercise during the period of testosterone administration. As an hypothetical example, one might not expect to see a large increase in the maximal flight speed of birds that were never allowed to fly following administration of exogenous testosterone. Indeed, Gallotia galloti lizards given exogenous testosterone were compared to lizards given sham implants and there was no difference in maximal bite force at the end of the experiment (K. Huyghe, J.F. Husak, R. Van Damme, M. Molina-Borja, A. Herrel, in review), despite increases in mass of the jaw muscles in testosterone-supplemented males. One possible explanation for this result is that these lizards did not “train” their jaw muscles enough while in captivity to increase muscle mass sufficiently to result in a measurable enhancement of performance. It is also possible that receptor density is very low or becomes low in trained muscles. Nevertheless, while training in animals seems straightforward in principle, in practice it is far trickier, and there also appear to be striking differences among species in the effects of training. Whereas some studies of mammals have successfully increased performance through training in a laboratory (Brooks and Fahey 1984 ; Astrand and Rodahl 1986 ), similar studies with lizards have found no effect (Gleeson 1979 ; Garland et al. 1987 ). In addition, while training might be successful with animals acclimated to a laboratory setting, inducement of stress, with a concomitant effect on corticosterone (Moore and Jessop 2003 ), and potentially circulating testosterone levels, is a significant confounding factor. Another complementary option is to use field studies, where experimental groups are released into the wild to “train” themselves while accomplishing their day-to-day tasks and performing naturally. Of course, this approach also cannot take into account variation in “training” within experimental groups, as individuals will likely use their performance traits in different ways when left to their own devices. Consequently, this approach could result in unpredictable results in how hormones impact performance, unless one accepts the unlikely assumption that all experimental animals are performing in the same ways. Further, a field approach also does not take into account other “pleiotropic” effects of increased (or decreased) testosterone on the phenotype (e.g., increased activity or conspicuousness to predators), which can eliminate potential benefits to fitness from enhanced performance due to testosterone supplementation.

Studies seeking to manipulate performance with testosterone supplementation should also consider the timing of experiments. For example, testosterone should ideally be increased or decreased during times when the hypothalamic–pituitary–gonad (HPG) axis is responsive and receptors are expressed in the appropriate target tissues. Seasonal sensitivity of the male HPG axis is well documented (Fusani et al. 2000 ; Jawor et al. 2006 ; Ball and Ketterson 2008 ), and such effects should be considered. For example, male green anoles ( Anolis carolinensis ) given exogenous testosterone after the end of the breeding season in a laboratory setting did not increase head size or bite-force performance (J. Henningsen, J. Husak, D. Irschick, and I. Moore, unpublished data), presumably because some or all of the relevant target tissues were no longer sensitive to androgens. On the other hand, male brown anoles ( Anolis sagrei ) did show enhanced maximal bite force when testosterone was supplemented at the beginning of the breeding season when the target tissues are presumably sensitive to androgens (Cox et al., in press). Timing of experimentation is thus critical for designing studies examining hormonal effects, and the interaction between timing and training should also be considered, as training effects may be relevant for some seasonal periods, but not for others.

A related issue concerns how much hormone to administer to experimental subjects. Studies of human steroid use typically involve supraphysiological doses of testosterone, as this is the typical regimen for steroid-abusing athletes (George 2003 ; Hartgens and Kuipers 2004 ). Indeed, many studies of steroid use by humans have been criticized for having experimental groups using physiological doses of testosterone. However, such criticism of seemingly unrealistic dosages highlights the differing goals of studies on human and non-human animals. Whereas studies of humans are focused on the role of supraphysiological doses on performance, those of nonhuman animals are more broadly interested in whether circulating testosterone affects performance within more natural bounds of variation (reviewed by Fusani et al. 2005 ; Fusani 2008 ). Supraphysiological doses can result in unexpected, or even counterintuitive, effects because endocrine systems tend to be homeostatic and compensatory after disruption via up- or down-regulation of various components within the system (Brown and Follett 1977 ).

There are few data on how testosterone affects dynamic performance during different stages of development, either in humans or in non-human animals. Practically all studies examining the effects of exogenous testosterone on humans have been on adults (reviewed by Hartgens and Kuipers 2004 ), but an increasing area of concern is steroid use by teenagers (Johnston et al. 2005 ). Because they are still developing physically, steroids may have dramatically different effects on dynamic performance in developing juveniles versus older adults. For example, steroid use is known to cause closure of growth plates of long bones (George 2003 ), potentially preventing growth to full height. Any manipulative hormone study examining effects on dynamic performance should also take baseline circulating levels into account, as there may be striking differences among age groups. For example, among sexually mature male green anole lizards in a well-studied New Orleans, Louisiana (USA) population, smaller “lightweight” males have lower circulating testosterone levels (Husak et al. 2007 , 2009b ), relatively smaller heads, and lower bite forces than do larger “heavyweight” males (see Lailvaux et al., 2004; Vanhooydonck et al., 2005a), with the difference apparently due to age (Irschick and Lailvaux 2006). Smaller males with low testosterone levels seem unable to produce higher levels (Husak et al. 2009b ), suggesting that testosterone levels are likely suppressed until a critical body size when the individuals become competitive with larger males. At this body size, elevated testosterone levels may accelerate growth of the head and increase bite force, although more data are needed to test this hypothesis. This ontogenetic increase in testosterone levels suggests that exogenous administration will have quite different effects on different age groups. For example, many hormones exert threshold effects (reviewed in Hews and Moore 1997 ) in which increased amounts above a threshold level produce little noticeable effect, suggesting that exogenous administration may accomplish little for larger lizards already with high testosterone levels, but may have substantial effects on smaller lizards with low testosterone levels.

In this context, long-term studies in animal species that focus on younger individuals (see Cox and John-Alder 2005 and references therein) might be useful for understanding the potential costs and benefits of hormones in improving or decreasing dynamic performance. Scientists are well-aware of some of the short-term activational effects of testosterone in humans and nonhuman animals, but while some long-term effects of supraphysiological doses on human health are recognized (see Hartgens and Kuipers 2004 ), we know far less about long-term effects of elevated (but not supraphysiological) testosterone levels on longevity and lifetime reproductive success of nonhuman animals. Ethical considerations may preclude long-term hormone implantation in humans and nonhuman animals, but correlating natural variation in testosterone levels both with performance traits and with other demographic features, such as longevity and lifetime reproductive success, would be useful for understanding chronic effects. Elegant studies with the dark-eyed junco ( Junco hyemalis ) (Ketterson et al. 2001 ; Reed et al. 2006 ) show complex trade-offs between different components of reproductive success (e.g., investment in extra-pair fertilizations versus parental care) as a result of testosterone supplementation; other similar trade-offs might be occurring over longer time spans in other animal species.

Despite popular interest in steroids and their effects on human athletic performance, we still lack a broad understanding of the effects of testosterone on performance in different animal species.

Our review of the literature on human steroids highlights several issues that could prove useful for integrative biologists interested in determining links among hormones, morphology, performance, and fitness in nonhuman animal species. First, studies of steroid use by humans reveal many caveats related to experimental design and interpretation that should be considered by those studying nonhuman animals (e.g., training, diet, dosage effects). Second, because of conflicting results of testosterone on different performance traits (e.g., burst performance versus endurance), more data are needed for such biomechanically opposing performance traits; testosterone may enhance multiple kinds of performance in some species, and only one kind in another. Third, while testosterone may have some general effects on dynamic performance in vertebrates, are there other hormones (e.g., juvenile hormone) that play a similar role in invertebrates? Finally, human steroid abusers often use various systems of “stacking”, where multiple drugs are taken in a specific order (George 2003 ), and such regimens are believed, by those who use them, to markedly increase dynamic performance. However, few studies have specifically examined how these regimes affect performance, or how the different regimes may be more, or less, effective in enhancing performance, either in humans or in non-human animal species. Furthermore, such practices are not restricted to multiple androgens, but may also include other hormones, such as growth hormone and insulin-like growth factor-I, which may, when taken exogenously, also enhance athletic performance and other aspects of the phenotype (Gibney et al. 2007 ). In this manner, the interactive effects of different hormone regimens for increasing animal performance are highly understudied. In conclusion, we have advocated an integrative approach for studying the evolution of morphology, function, and endocrine systems, and increased collaboration between researchers interested in human and in other animal systems may prove fruitful for both groups.

Financial support was provided by the National Science Foundation (IOS 0421917 to DJI and IOS 0852821 to I. T. Moore, JFH and DJI).

We are thankful to the symposium participants for fruitful discussions about hormones and performance. We thank the Society for Integrative and Comparative Biology, especially the Divisions of Animal Behavior, Comparative Endocrinology, and Vertebrate Morphology, for providing logistical and financial support.

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  • Published: 01 June 2022

Anabolic–androgenic steroid use is associated with psychopathy, risk-taking, anger, and physical problems

  • Bryan S. Nelson 1 ,
  • Tom Hildebrandt 2 &
  • Pascal Wallisch 1  

Scientific Reports volume  12 , Article number:  9133 ( 2022 ) Cite this article

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  • Human behaviour

Previous research has uncovered medical and psychological effects of anabolic–androgenic steroid (AAS) use, but the specific relationship between AAS use and risk-taking behaviors as well as between AAS use and psychopathic tendencies remains understudied. To explore these potential relationships, we anonymously recruited 492 biologically male, self-identified bodybuilders (median age 22; range 18–47 years) from online bodybuilding fora to complete an online survey on Appearance and Performance Enhancing Drug (APED) use, psychological traits, lifestyle choices, and health behaviors. We computed odds ratios and 95% confidence intervals using logistic regression, adjusting for age, race, education, exercise frequency, caloric intake, and lean BMI. Bodybuilders with a prior history of AAS use exhibited heightened odds of psychopathic traits, sexual and substance use risk-taking behaviors, anger problems, and physical problems compared to those with no prior history of AAS use. This study is among the first to directly assess psychopathy within AAS users. Our results on risk-taking, anger problems, and physical problems are consistent with prior AAS research as well as with existing frameworks of AAS use as a risk behavior. Future research should focus on ascertaining causality, specifically whether psychopathy is a risk associated with or a result of AAS use.

Introduction

An estimated 6% of males globally 1 (including 2.9–4 million Americans 2 ) have used anabolic–androgenic steroids (AAS) such as methyltestosterone, danazol, and oxandrolone, which are a series of synthetic variants of the male sex hormone testosterone that increase lean muscle protein synthesis without increasing fat mass 3 , 4 . Although there are medical uses such as for AIDS-related wasting syndrome 5 , AAS are commonly used by individuals for the purposes of bodybuilding and appearance modification 2 , 3 , 6 . In these cases, doses are commonly 10 to 100 times higher than clinical doses and are typically “cycled” intermittently (i.e., used for a few months, stopped to minimize the stress that AAS impart on the body, then resumed shortly thereafter) 3 , 7 . AAS have a 30% dependence rate among long-term users, higher than many other prescription or illicit drugs such as cocaine and have been linked to medical issues such as liver and kidney damage, cardiovascular problems, testicular atrophy, infertility, hair loss, and gynecomastia 2 , 3 , 7 , 8 , 9 , 10 . AAS use is strongly associated with other substance abuse 8 , 9 , 11 , 12 , and users often exhibit negative, although idiosyncratic, psychological issues 8 , 13 , 14 , 15 , 16 , 17 . Some users report delusions of grandeur and invincibility, while others experience depression and various mood disturbances 8 , 18 , 19 , 20 . As dosage increases, AAS users may become impulsive, moody, aggressive, or even violent 9 , 18 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 . Recent neurobiological studies have focused on effects of AAS on central nervous system functions such as cognition, anxiety, depression, and aggression 10 , 28 , 29 . In recent imaging studies, AAS use was associated with cortex thinning as well as decreased gray matter and increased right amygdala volume 30 , 31 , 32 . AAS use seems to accelerate brain aging through oxidative stress and apoptosis 33 , 34 , 35 , is associated with lower cognitive function 36 , 37 , and may disrupt normal neuronal function in the forebrain, which can increase anxiety and aggressiveness and diminish inhibitory control 10 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 . Increased depression has been frequently observed during AAS withdrawal 32 , 46 .

One area that remains understudied among AAS users is psychopathy, a personality disorder characterized by shallow emotional affect, lack of empathy, and antisocial behavior 47 , 48 , 49 . Psychopathy research has frequently associated psychopathy with violence, repeated imprisonment, disrespect for authority, and substance misuse/abuse 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 . There is growing evidence that AAS use may be associated with psychopathy, including a direct association between AAS and psychopathy in an Iranian sample 56 as well as numerous reports of associations between AAS use and violent crime or “roid rage” 19 , 21 , 22 , 23 , 25 , 27 , 57 . Prior studies examining AAS use and elements of the “Dark Triad” and “Big Five” personality traits suggest that the relationship between AAS use and both violence and risk-behaviors may be due to self-regulatory deficits and low conscientiousness, and that AAS use is predicted by narcissism, low agreeableness, neuroticism, impulsivity, and inability to delay gratification 56 , 58 . Hauger et al. 28 recently identified significantly lower emotion recognition in AAS dependent users compared to AAS non-using weightlifters, suggesting that this lower emotion recognition may contribute to the higher frequencies of antisocial traits that AAS users have previously reported 59 , 60 . Antisocial personality disorder, which is characterized by the disregard for laws and norms, irritability, and the failure to regard the safety of self and others 61 has been suggested as the mechanism that underlies the link between AAS use and aggression 3 , 9 , 60 , 62 , 63 . Conceptually, there are overlaps between antisocial personality disorder and psychopathy 64 . We therefore argue that psychopathic traits among AAS users are worth exploring.

Thus, the present study assessed whether AAS users were more likely than nonusers to exhibit psychopathic traits, risk-taking behaviors such as sharing needles, anger problems such as getting into altercations, emotional problems such as panic attacks and depression, cognitive problems such as difficulty remembering, and physical problems such as hair loss. We hypothesized that AAS users would display heightened odds of psychopathic traits, substance use risk-taking behaviors, sexual risk-taking behaviors, anger problems, emotional stability problems, cognitive problems, depressive symptoms, anxiety symptoms, impulsivity symptoms, and physical problems, although we recognize that many of these traits are highly idiosyncratic in nature. Finally, we hypothesized there is a dose-dependent relationship between these traits and the variety of substances used as well as the number of cycles.

Participants and procedure

This study was approved by the NYU Committee on Activities Involving Human Subjects and we conducted in accordance with the Declaration of Helsinki principles. We anonymously recruited a large online sample of 492 (Mean age = 22.9, SD age = 4.3) adult biologically male bodybuilders and asked them questions about their Appearance and Performance Enhancing Drug (APED) use (if any), exercise and dietary habits, psychological states, risk-taking behaviors, and any physical problems they might have experienced. The anonymous internet survey was posted to online fitness fora in fall 2015. All participants provided informed consent prior to their participation. Participants had the option to enter an online raffle for one of twenty $50 Amazon gift cards, which were distributed via email.

The following subsections are presented in the same order as the online survey.

Diet and exercise

Participants reported how often they had exercised in the past month (every day, most days, some days, very rarely/never) and rated their caloric intake in the past month on a 5-point ordinal scale (1 = extreme restriction of calories, 5 = extreme over-consumption of calories). We measured caloric intake in terms of restriction, maintenance, or surplus rather than total calories per day because participants likely vary in caloric requirements (i.e., 3000 cal/day may be a surplus for some but a deficit for others).

Appearance and performance enhancing drugs

Each participant indicated whether he had ever used oral, injectable, or topical AAS (“yes, currently,” “yes, formerly,” “no, but considered taking,” “no, never considered taking” for each). Additionally, participants reported how many AAS cycles they had completed and responded whether they had ever used the following APEDs (each with “yes”/”no” options): Testosterone, Dianabol (Methandrostenolone), Deca Durabolin (Nandrolone Decanoate), Winstrol (Stanozolol), Anadrol (Oxymetholone), Human Growth Hormone (Somatropin), Synthol, Anti-Estrogens, Fat Burners (Insulin, Clenbuterol, Cytomel, Cynomel), Trenbolone, or Anavar.

Self-reported events

Participants rated each of the following items as “yes, currently,” “yes, formerly,” or “no, never”.

General events Participants self-reported whether they experienced the following events: depression, increased number of mood swings, getting into altercations, panic attacks, irritability, lack of frustration tolerance, aggression, difficulty focusing, racing thoughts, difficulty making decisions, difficulty remembering, suicidal thoughts, acne, trouble sleeping, water retention, hair loss, changes in appetite, and heart problems.

Risk-taking behavior Participants indicated whether they had engaged in or experienced the following: unprotected sex, sex with multiple partners, sexually transmitted disease or infection (STD), sharing needles, reusing needles, using stimulants without prescription (such as crack, powdered cocaine, methamphetamine, amphetamine, or ecstasy [MDMA]), using opiates without prescription (such as heroin, morphine, codeine, or Oxycontin), using hallucinogens without prescription (such as LSD, mescaline, and psilocybin), using depressants without prescription (such as Valium, Xanax, Librium, and barbiturates), drinking alcohol, smoking tobacco, and smoking marijuana.

Impulsivity

We used the Barratt Impulsiveness Scale to quantify impulsivity (BIS-11) 65 . Participants responded to 30 statements such as “I often have extraneous thoughts” using a 4-point ordinal rating scale (1 = rarely/never, 4 = almost always/always). The BIS-11 displayed strong reliability in this sample (Cronbach’s α = 0.84).

Psychopathic traits

We employed the Levenson Self-Report Psychopathy Scale (LSRP) to assess psychopathy 66 . The scale has 26 items graded on a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree) and was strongly reliable in this sample (Cronbach’s α = 0.88).

We assessed anxiety with the Generalized Anxiety Disorder 7-item Scale (GAD-7) 67 . Participants responded to each of the seven items such as “being so restless it is hard to sit still” on a 4-point ordinal rating scale (0 = not at all, 3 = nearly every day). The GAD-7 displayed excellent internal consistency (Cronbach’s α = 0.89). Possible scores range from 0 to 21.

We included the 10-item Center for Epidemiologic Studies Short Depression Scale (CES-D 10) 68 to measure depression. Participants rated statements such as “I felt lonely” on a 4-point ordinal rating scale (0 = rarely or none of the time, 3 = all the time). The CES-D 10 was highly reliable (Cronbach’s α = 0.82), with possible scores ranging from 0 to 30.

Aggravation

Participants responded to the 7-item aggravation subscale of the State Hostility Scale 69 , 70 . In the subscale, participants rate possible descriptions of their current mood (e.g., “stormy” or “vexed”) on a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree). The aggravation subscale of the State Hostility Scale had strong reliability (Cronbach’s α = 0.90).

Demographic questions

Lastly, participants reported their age (years), height (inches), weight (pounds), body fat percentage, racial background, and level of education.

Statistical analysis

The survey was convenience sampled, with no pre-specified sample size or power calculation. For our primary analysis, we grouped participants who responded “yes, currently” or “yes, formerly” to having used AAS (oral, injectable, or topical) as AAS users (n = 154, 31.3%). We considered those who responded “no, but considered taking” or “no, never considered taking” to be AAS nonusers (n = 338, 68.7%). We also conducted a secondary analysis using all four categories (current AAS users (n = 121, 24.6%); former AAS users (n = 33, 6.7%); AAS nonuser, considered using (n = 200, 40.7%); AAS nonuser, never considered using (n = 138, 28.0%)).

Both AAS cycle experience and APED variety were self-reported. APED variety was the number of different APED types used (the number each participant responded “yes” to taking of Testosterone, Dianabol (Methandrostenolone), Deca Durabolin (Nandrolone Decanoate), Winstrol (Stanozolol), Anadrol (Oxymetholone), Human Growth Hormone (Somatropin), Synthol, Anti-Estrogens, Fat Burners (Insulin, Clenbuterol, Cytomel, Cynomel), Trenbolone, and Anavar). AAS cycle experience was the number of AAS cycles participants reported. If the participant was an AAS nonuser, then both APED variety and AAS cycle experience were scored as 0.

We grouped traits of interest into the following categories: psychopathic traits, substance use risk-taking behavior, sexual risk-taking behavior, anger problems, emotional stability problems, cognitive problems, depressive symptoms, anxiety symptoms, impulsivity symptoms, and physical problems. Following Brinkley et al. 71 , we considered participants in the top third of the LSRP distribution to have psychopathic traits. We considered any participant that reported sharing needles, reusing needles, hallucinogen use, stimulant use, depressant use, or opiate use as engaging in substance use risk-taking. Similarly, any participant that reported an STD, engaging in unprotected sex, or having multiple sexual partners was categorized as having sexual risk-taking behavior. Any participant scoring in the top half of the aggravation subscale of the State Hostility Scale, reporting physical altercations, or reporting increased aggression was categorized as having anger problems. Participants who reported mood swings, lower frustration tolerance, or irritability were considered to have emotional stability problems while participants with difficulty remembering, difficulty focusing, or trouble making decisions were considered to have cognitive problems. We considered participants with depressive symptoms as those that reported suicidal thoughts, reported increased depression, or had a CES-D 10 score greater than 10 (the established cut point 68 ). Those with anxiety symptoms either had a GAD-7 score greater than the established cut point 67 of 8 or reported panic attacks. A participant who reported racing thoughts or who scored in the top half of the Barratt Impulsiveness Scale was considered to have impulsivity symptoms. Finally, we considered participants to have physical problems if they reported heart problems, appetite changes, water retention, acne, or hair loss.

We used logistic regression to assess possible associations between these traits of interest and AAS use, number of AAS cycles, and variety of APEDs used. We computed odds ratios (OR) with 95% confidence intervals (CI). All analyses adjusted for age, race, education, exercise frequency, caloric intake, and lean BMI. Age, race, and education were included as basic demographic variables, while exercise frequency, caloric intake, and lean BMI were included to account for differences in bodybuilding goals, success, and dedication. We chose to calculate lean BMI to assess how muscular participants were. We used the standard (kg/m 2 ) BMI formula but used each participant’s lean bodyweight instead of his total bodyweight. Lean body weight was calculated by using each participant’s self-reported body fat percentage to determine how much he weighed excluding his body fat (weight in kg * (100%-bodyfat%)). Given that both psychopathy and AAS use are associated with illicit drug use 21 , we conducted a post hoc subgroup analysis among participants without history of polysubstance use (3 or more different drug classes) to ensure any association between AAS use and psychopathic traits was not confounded by polysubstance use. All analyses were conducted in R (version 3.5.1).

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of New York University.

Consent to participate

Participants provided informed consent prior to their participation in this anonymous internet survey.

Participant characteristics are listed in Table 1 . Most participants were younger than 25 years old (56.5% of AAS users; 79.0% of AAS nonusers), white (85.7% of AAS users; 77.5% of AAS nonusers), and had education beyond high school (75.3% of AAS users; 59.1% of AAS nonusers). The majority in each group exercised most days of the week (79.2% of AAS users; 74.8% of AAS nonusers) and were attempting to gain weight (51.3% of AAS users; 51.2% of AAS nonusers). For AAS users and nonusers, the median (Q1-Q3) lean BMI was 23.6 (22.3–25.4) and 21.6 (20.3–23.3) kg/m 2 . AAS users began use at a median (Q1-Q3) of 21 (20–24) years, had completed 2 (1–3) AAS cycles, and used 4 (2–5) different APED types; 78.6% (121/154) were current AAS users. Among AAS nonusers, 59.2% (200/338) had considered using AAS.

Tables 2 and 3 summarize traits of interest and specific substance use risk-taking behaviors by AAS use status; 25.8% (39/154) of AAS users and 10.2% (34/338) of AAS nonusers had a history of polysubstance use. AAS users had over twice the odds of exhibiting psychopathic traits (OR = 2.50, 95% CI 1.52–4.15), over three times the odds of engaging in substance use risk-taking behaviors (OR = 3.10, 95% CI 1.97–4.93), nearly twice the odds of engaging in sexual risk-taking behaviors (OR = 1.79, 95% CI 1.01–3.26), nearly twice the odds of experiencing anger problems (OR = 1.71, 95% CI 1.02–2.95), and over twice the odds of exhibiting physical problems (OR = 2.23, 95% CI 1.16–4.51) compared to AAS nonusers (Table 4 ). In a post hoc subgroup analysis, AAS users without history of polysubstance use had higher odds of psychopathic traits compared to nonusers without history of polysubstance use (OR = 2.73, 95% CI 1.54–4.90).

In secondary analyses with four levels of AAS use, AAS nonusers who considered using had higher odds of psychopathic traits (OR = 2.19, 95% CI 1.27–3.87), substance use risk-taking (OR = 3.51, 95% CI 2.06–6.14), sexual risk-taking (OR = 3.38, 95% CI 2.00–5.78), anger problems (OR = 3.16, 95% CI 1.86–5.42), emotional stability problems (OR = 1.87, 95% CI 1.16–3.01), depressive symptoms (OR = 2.12, 95% CI 1.32–3.44), and impulsivity symptoms (OR = 2.17, 95% CI 1.31–3.61) compared to AAS nonusers who never considered using; former AAS users had lower odds of both anxiety symptoms (OR = 0.30, 95% CI 0.08–0.84) and impulsivity symptoms (OR = 0.33, 95% CI 0.14–0.74) compared to AAS nonusers who considered using; and current AAS users had higher odds of both impulsivity symptoms (OR = 2.92, 95% CI 1.27–6.84) and physical problems (OR = 5.86, 95% CI 1.83–19.74) compared to former AAS users.

Lastly, we assessed possible relationships between (i) the number of different APED types used and (ii) the number of AAS cycles with the same traits of interest as before. Each additional type of APED used was associated with a 19% increase in the odds of psychopathic traits (OR = 1.19, 95% CI 1.07–1.33), a 24% increase in the odds of substance use risk-taking (OR = 1.24, 95% CI 1.12–1.38), an 18% increase in the odds of sexual risk-taking (OR = 1.18, 95% CI 1.02–1.38), a 15% increase in the odds of emotional stability problems (OR = 1.15, 95% CI 1.04–1.27), and a 33% increase in the odds of physical problems (OR = 1.33, 95% CI 1.12–1.66). For every one-unit increase in the number of AAS cycles, there was a 26% increase in the odds of substance use risk-taking (OR = 1.26, 95% CI 1.10–1.46) and an 85% increase in the odds of physical problems (OR = 1.85, 95% CI 1.29–3.01).

In our online survey of adult biologically male bodybuilders, we found AAS use was associated with higher odds of psychopathic traits, both for AAS users compared to nonusers as well as for increased APED variety. Importantly, this association was also present among participants with no history of polysubstance use. It is not certain whether AAS use predicts psychopathic traits or if the existence of psychopathic traits may actually be a risk factor for AAS use. We note that AAS nonusers who considered AAS use had over twice the odds of psychopathic traits compared to AAS nonusers who never considered AAS use. A recent study of 285 competitive athletes reported that Machiavellianism and psychopathy explained 29% of the variance in positive attitude toward AAS 72 . This is supported generally by the well-established association between psychopathic traits and risk-taking behaviors such as substance abuse 48 . In that case, a large proportion of bodybuilders willing to make the jump to using AAS may already have pre-existing psychopathic traits. Psychopathy is related to both antisocial personality disorder and conduct disorder, each of which is associated with AAS use 9 , 60 . Conduct disorder in particular is a major risk factor for AAS use 9 that cannot be entirely explained by use of other drugs 59 . The relationship may be dynamic; bodybuilders with psychopathic tendencies may be more willing to begin AAS in the first place. Subsequently, these traits might be amplified either chemically by AAS use or psychologically by the environment; prior work has shown the difference between psychopaths and non-psychopaths in emotional-regulatory activity in the aPFC is modified by endogenous testosterone level 73 . With this in mind, longitudinal research is needed to further explore the causal nature of this relationship.

Our study is one of many to link AAS use substance use risk-taking behaviors 74 , 75 and sexual risk-taking behaviors 59 , 76 . It is difficult to ascertain the specific relationship between AAS use and risk-taking. Unlike physical, psychological, cognitive, and anger problems, which have all had experimental and translational research done to strengthen causal interpretations of such links 16 , 77 , there has not been experimental work to test whether risk-taking behaviors are caused by AAS use. In fact, it is important to consider that AAS use is itself a risk behavior, and another form of substance use, so AAS users may already engage in many other risk-taking behaviors prior to their first use. This may be especially true in light of our findings that AAS nonusers who considered AAS use had over three-times the odds of both substance use and sexual risk-taking behaviors compared to AAS nonusers who never considered AAS use, as well as our results regarding APED variety and AAS cycle experience. AAS users willing to try more types of APEDs or willing to undergo more AAS cycles may be more likely to also engage in risk-taking behaviors. Perhaps the relationship between AAS and risk-taking behaviors is bidirectional and interactive, where athletes that engage in these risk behaviors such as illicit drug use experiment with AAS, which may lower their inhibitions to take further risks.

Our finding that AAS users have higher odds of experiencing anger problems is in line with prior research 16 , 19 , 20 . Notably, anger has been previously reported as both a potential risk factor 78 as well as a potential outcome 27 . We did not observe associations between AAS use and emotional stability problems, cognitive problems, depressive symptoms, anxiety symptoms, or impulsivity symptoms. Prior research has identified various psychological and cognitive traits among AAS users such as depression, impulsivity, and mania 18 , 19 , 20 , but they are generally idiosyncratic in nature 8 , 79 , 80 , 81 . We do note that AAS nonusers who considered AAS use had higher odds of emotional stability problems, depressive symptoms, and impulsivity symptoms compared to AAS nonusers who never considered AAS use, former AAS users had lower odds of anxiety symptoms and impulsivity symptoms compared to AAS nonusers who considered AAS use, and current AAS users had higher odds of impulsivity symptoms compared to former AAS users. These findings comparing AAS nonusers who considered vs. never considered AAS use are consistent with prior research about factors relating to the decision to use AAS, including research on the “Big Five” personality traits 58 . Additionally, we observed increased odds of emotional stability problems with increased APED variety. Lastly, our hypothesis about physical problems was supported for AAS users compared to nonusers as well as the dose dependent response in relation to increased APED variety and increased AAS cycle experience. These findings are consistent with prior studies 3 , 8 , 10 , 32 .

There are several limitations. Although we successfully elicited responses from real-world users of AAS, there remain questions about how representative our sample is. AAS users in our sample were relatively new users (median of 2 prior cycles). Our findings may have been different with a group of more experienced users. It is also possible that our online survey was more likely to attract individuals with psychopathic traits or that AAS users with psychopathic traits are more willing to take an online survey than other users. We note that > 50% of AAS users and nonusers were considered to have substance use risk-taking, sexual risk-taking, anger problems, emotional stability problems, cognitive problems, depressive symptoms, impulsivity symptoms, and physical problems. Lastly, this cross-sectional study is entirely correlational and any attempts to speculate about causality should be made with extreme caution. Further prospective or experimental studies are needed. In light of the findings on Machiavellianism and psychopathy in relation to willingness to use AAS 72 , it would be interesting to also examine the link to narcissism and self-esteem/insecurity 82 . We wonder whether self-esteem or narcissistic traits could play an additional role in the motivation to begin AAS use, given the known downsides.

This study is among the first to directly assess psychopathy within AAS users. Our results on risk-taking, anger problems, and physical problems are consistent with prior AAS research as well as with existing frameworks of AAS use as a risk behavior. Increased psychopathic traits in AAS users may serve as the underlying mechanism to predict increased anger problems (see 60 regarding antisocial personality disorder as a mechanism between AAS and aggression). Although the present study highlights the relationship between AAS use and psychopathic traits, future research should emphasize possible causal explanations and try to elucidate the directionality of this relationship. Additionally, the mechanisms between AAS use and risk and violent behaviors should be further explored.

Data availability

All data generated or analyzed during this study are included in this published article’s supplementary information files. R code used in data analysis can be made available upon reasonable request to the corresponding author.

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We thank Ward Pettibone and Andre Nakkab for administrative assistance. This work was supported by the New York University Dean’s Undergraduate Research Fund.

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Nelson, B.S., Hildebrandt, T. & Wallisch, P. Anabolic–androgenic steroid use is associated with psychopathy, risk-taking, anger, and physical problems. Sci Rep 12 , 9133 (2022). https://doi.org/10.1038/s41598-022-13048-w

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steroids research paper

Anabolic steroids

Affiliation.

  • 1 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. [email protected]
  • PMID: 12017555
  • DOI: 10.1210/rp.57.1.411

The term "anabolic steroids" refers to testosterone derivatives that are used either clinically or by athletes for their anabolic properties. However, scientists have questioned the anabolic effects of testosterone and its derivatives in normal men for decades. Most scientists concluded that anabolic steroids do not increase muscle size or strength in people with normal gonadal function and have discounted positive results as unduly influenced by positive expectations of athletes, inferior experimental design, or poor data analysis. There has been a tremendous disconnect between the conviction of athletes that these drugs are effective and the conviction of scientists that they aren't. In part, this disconnect results from the completely different dose regimens used by scientists to document the correction of deficiency states and by athletes striving to optimize athletic performance. Recently, careful scientific study of suprapharmacologic doses in clinical settings - including aging, human immunodeficiency virus, and other disease states - supports the efficacy of these regimens. However, the mechanism by which these doses act remains unclear. "Anabolism" is defined as any state in which nitrogen is differentially retained in lean body mass, either through stimulation of protein synthesis and/or decreased breakdown of protein anywhere in the body. Testosterone, the main gonadal steroid in males, has marked anabolic effects in addition to its effects on reproduction that are easily observed in developing boys and when hypogonadal men receive testosterone as replacement therapy. However, its efficacy in normal men, as during its use in athletes or in clinical situations in which men are eugonadal, has been debated. A growing literature suggests that use of suprapharmacologic doses can, indeed, be anabolic in certain situations; however, the clear identification of these situations and the mechanism by which anabolic effects occur are unclear. Furthermore, the pharmacology of "anabolism" is in its infancy: no drugs currently available are "purely" anabolic but all possess androgenic properties as well. The present review briefly recapitulates the historic literature about the androgenic/anabolic steroids and describes literature supporting the anabolic activity of these drugs in normal people, focusing on the use of suprapharmacologic doses by athletes and clinicians to achieve anabolic effects in normal humans. We will present the emerging literature that is beginning to explore more specific mechanisms that might mediate the effects of suprapharmacologic regimens. The terms anabolic/androgenic steroids will be used throughout to reflect the combined actions of all drugs that are currently available.

Publication types

  • Anabolic Agents* / administration & dosage
  • Anabolic Agents* / pharmacology
  • Androgens / administration & dosage
  • Androstenedione / administration & dosage
  • Biomechanical Phenomena
  • Central Nervous System / drug effects
  • Central Nervous System / physiology
  • Dose-Response Relationship, Drug
  • Muscles / anatomy & histology
  • Muscles / drug effects
  • Muscles / physiology
  • Anabolic Agents
  • Androstenedione

Sample research paper about steroids

Drugs generally referred to as ‘steroids’ can be categorized as anabolic and corticosteroids. Corticosteroids are drugs prescribed by the doctors to help managing inflammation in the human body and mostly used in conditions such as lupus and asthma. They are, in fact, not similar to the anabolic steroids which receive a high degree of media attention as they are used by some bodybuilders and athletes. Anabolic steroids can boost the ability of body to prevent breakdown of muscle and increase muscle growth. (Llewellyn, 2007)

To understand steroids and how they work in the body, it is pertinent to define the concept of Anabolic steroids. Anabolic means building up, as contrary to catabolic which means breaking down. The term ‘Anabolic steroids’ is related to synthesizing or manufacturing derivatives specifically of the male hormone, testosterone. There are two major functions of testosterone on the body, the androgenic and anabolic effect. The anabolic effect is mainly responsible for muscular development, growth and the adult male’s masculine body contour. The androgenic impact provokes the growth of the male secondary features after puberty, resulting in the growth of pubic hair, beard, voice change and development of penis.

Anabolic steroids basically work by arousing the anabolic effect either by binding or plugging into the cells that ultimately help in generating new proteins specifically in the cells. This enhanced biological activity is known as an enhancement in Ribonucleic Acid Activity. The creation of new proteins ultimately results in increasing muscle strength and size. The steroids increase or stimulate this particular biological process by connecting to the receptor sties.

Steroids can also increase retention of nitrogen which is also a biological activity. Nitrogen is present in proteins where it performs building tissues. The users of steroids experience a constructive nitrogen balance which is a preferred condition where ingestion of nitrogen from protein is much more than excretion of nitrogen.

Anabolic steroids are particular drugs similar with the chemical structure of the human body’s sex hormone ‘testosterone’, made naturally within body. Testosterone ultimately directs the body to enhance or produce male features discussed above. When the level of testosterone is increased by the anabolic steroids in blood, they result in stimulating muscle tissue to grow stronger and larger. However, the impact of excess testosterone circulating in the human body can be much harmful in the long run. (Willey, 2007)

There is no concrete evidence that exclusive high steroids doses can result in muscle growth through a specific chemical effect. In most of the animal species, the much higher quantity of anabolic steroids produces no significant muscle growth as a normal dose would. Nevertheless, evidence suggests that steroids increase muscle growth provided they are taken with scrupulous physical training and also an increased protein diet.

Once a person takes drug, it is processed in the body including four major processes; absorption; distribution; metabolism; and excretion. In ‘Absorption’, drugs are generally administered orally or intravenously. In case, drugs are processed orally, then absorption is more complex as compared to the scenario when administered intravenously. The ‘Distribution’ process involves the drug transportation all the way through blood stream. ‘Metabolism’ can be described as the chemical change created by the drug in the body. The main place where this change occurs is the liver where most of the people face problems by using steroids. ‘Excretion’ is the removal of drug from the person’s body. (Willey, 2007)

Anabolic steroids are, in fact, more toxic to the liver where they are excreted and metabolized. It is firmly believed that the side effects resulting from usage of steroids are actually dose related. Most of the body builders take high steroids than they actually need to view the desired results. However, it is not necessary to take four tablets when only one is effective.

The major risk associated with the steroids is a serious damage to liver. As is the case, the liver is more amazing and versatile organ in the body. Almost three pints of blood, in every minute, pass through liver. At one particular time, about ten percent of entire blood in the body is found in the liver. Liver stores, glycogen, copper, sugar, vitamin A, some B vitamins and also vitamin D. (Willey, 2007)

In case a liver is not working properly, the human body can face high complexities. When steroids are taken orally, they should be detoxified by liver via metabolism process already discussed. The liver then has to work much harder for abolishing toxins or poisonous substances produced by steroids. Resultantly, inflammation or hepatitis of the liver can take place. Hepatitis can lead directly to cirrhosis of the liver, a state of progressive scarring. Cirrhosis is a severe disease that kills all cells in the liver, ultimately resulting in liver failure. (Roberts, 2006)

Effects of steroids on Young Athletes

A primary objective of youth sports is to support young athletes observe and experience significant life lessons, developing a physically, healthy active lifestyle. Continuous improvement of young athletes is a vital part of the entire process. As discussed above, the anabolic steroids impact the metabolism in each and every cell. However, in some cells metabolism produce the required adaptation such as increase in the size of muscle, while in other cells creating complexities like changed lipid metabolism specifically in the liver.

Training, exercise or proper nutrition is needed for muscle growth without any extra amount of fat. For instance, in football, Olympic weight lifting and different other sports, the aim is to become explosively strong. In such cases, the steroids work in combination with a certain weight training and dietary regime particular to those sports. On the other hand, for long distance runners or road cyclists, the aim is to be capable in maintaining an extensive training load and at the same time keeping light body weight. As such anabolic steroids may be used to support these athletes recovering from such training. (More, 2004)

Anabolic steroids are specifically designed to take off the bodybuilding features of testosterone. The amount of testosterone can be significantly increased in the human body by using these anabolic steroids, which further supports the human body in muscle growth. As such the anabolic impact of steroids attracts attention of athletes who require an increase in strength and muscle mass.

An increasing number of young athletes use steroids as an instant shortcut for the purpose of performing better. However, when younger athletes use steroids either through injection or orally, they are, in fact, exposing their health and body to a wide array of threats. Buying or using steroids without a physician’s prescription is dangerous as well as illegal. (More, 2004)

Anabolic steroids have considerable effects on the moods of young athletes. Athletes taking steroids on regular basis become more irritable, aggressive and angrier, ultimately becoming depressed after they have stopped using steroids. In some cases, usage of steroids can also cause psychotic episodes. In case of boy athletes, steroids can not only terminate the growth of athlete but may cause facial blemishes, shrinking of testicles, the development of breasts and increased weight.

In girl athletes, steroids can result in the development of some male characteristics and acne can also be aggravated. More grave reactions, in young athletes of both sexes, have been associated with steroids like heart attacks, suicidal behavior and liver damage. As such it is essential for the coaches and parents to realize the phenomenon that anabolic steroids can have different grave side effects. Moreover the long-term risks associated with using steroids far outweigh the possible short-term benefits.

There are some exclusive factors related to using steroids by young athletes. Steroids load up a young athlete, especially in teenage, with synthetic testosterone. As discussed above, it can lead ultimately to premature puberty while among complexities are; premature puberty in young athletes using steroids with growth plates that are particularly open in bones causing such growth plates to close before time. (Roberts, 2006)

Several studies have highlighted a relation of steroid usage with different other high-risk attitudes such as having insecure sex, driving drunk and using other illegal drugs. Young athletes are placed in a high-risk group and as such using steroids intensifies the problem. A better solution to increase awareness about the negative and long-term effects of steroids in young athletes is to provide education about risks associated with steroids and programs for supervised confrontation training to increase substantial strength.

Difference of Steroid Abuse in Men and Women

Steroids, similar to all drugs, have many side effects- most of them can be dangerous for health while other simply undesirable. Because drugs treated as steroids can affect women and men differently, it is pertinent to separately focus on steroids abuse in both. Steroid abuse is found to be higher in men as compared with women, although the trend of abusing steroid among young women is increasing. People are motivated to abuse the steroid due to an intense desire for reducing fats in body, building muscles and improving performance in sports. Bodybuilders, according to an estimate, are the high users of anabolic steroids, while it is also widespread in other sportspersons. Some of the men abusing anabolic steroids view their body as weak and small, even if they are muscular and large. On the other hand, women abuse such drugs as they perceive their looks are obese, although they are actually muscular and lean.

Other reasons of abusing anabolic steroids by women include endeavors to lose weight. Many women eat healthy and attend gym when they are just few pounds away from normal weight, resorting to drugs. These women are more focused on different celebrities who although look thin but have considerable muscles. (Assael, 2007)

Even though, anabolic steroids assure a toned human body with specific muscle mass, yet thin. Women are of the view that recovery time from exercises is far less when they use anabolic steroids. Moreover, they also think that their mental capabilities become much shaper by using steroids. Women also abuse anabolic steroids as they perceive it to improve body image and self esteem along with increased sexual energy.

Most of the men abuse steroids to attain perfect body as they are in continuous scrutiny. Even though, the motive is becoming thin, it is, in fact, muscular body, that remains as the main attraction for abusing steroids by men. The general consensus is that the issues relating to body image commence in high school as well as in college, when men are viewed as sexual. The overall atmosphere of high schools and colleges is competitive and boys feel much insecure as compared with their friends. It has been highlighted that serious risks are related with steroid abuse, but most of the time people ignore the threats or not seeks support because they do not view themselves as drug users. (Assael, 2007)

Assael, S (2007) Steroid Nation: Juiced Home Run Totals, Anti-aging Miracles, and a Hercules in Every High School: The Secret History of America’s True Drug Addiction. ESPN; Ist edition

More, J (2004) Steroids, Sports, and Body Image: The Risks of Performance-Enhancing Drugs. Enslow Publishers

Llewellyn, W (2007) Anabolic 2007: Anabolic Steroids Reference Manual. Body of Science.

Roberts, A (2006) Anabolic Steroids: Ultimate Research Guide. Anabolic Books, LLC.

Willey, W (2007) Better Than Steroids. Trafford Publishing; Ist edition

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  • Indian Dermatol Online J
  • v.11(5); Sep-Oct 2020

Use of Topical Steroids in Dermatology: A Questionnaire Based Study

Sonali r. karekar.

Department of Pharmacology and Therapeutics, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India

Padmaja A. Marathe

Vetrivel babu nagarajan, uday s. khopkar.

1 Department of Dermatology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India

Siddhi B. Chikhalkar

Priyashree k. desai.

2 Department of Third Year MBBS Student, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India

Minakshi S. Dongre

Topical steroids, the most widely prescribed drugs in dermatology are being increasingly misused.

This study was conducted to assess knowledge and practices regarding the use of topical steroids and to analyze prescriptions containing topical steroids.

Subjects and Methods:

Following approval from the institutional ethics committee, participants were recruited as per the selection criteria and divided into those treated in the institution and those having outside prescription. They were administered a pre-validated questionnaire to assess knowledge and practices regarding the use of topical steroids.

Statistical Analysis Used:

Comparison of awareness between two patient categories was done using Chi-square test. Prescription variables were analyzed using descriptive statistics. Significance of P value was set at 0.05.

Out of 400 patients, 167 had external prescriptions whereas 233 were institutional patients. Only 5.5% of all patients knew about the type of drug prescribed whereas 31.25% were aware of the indication. A total of 33.75% of the patients knew topical steroids required a prescription and 5.6% said they were aware that topical steroid use was associated with side effects. Side effects were reported by 96 patients. Awareness regarding knowledge, indication, and need for prescription were significantly better in institutional patients whereas knowledge about side effects was lacking in both groups. Psoriasis was the most common indication overall whereas tinea was the most common indication (51.5%) among externally prescribed.

Conclusions:

Although this study showed that institutional patients had comparatively better knowledge than community-treated patients, there is a need to create more awareness among patients overall and implement measures to stop irrational prescribing practices in the community.

Introduction

Topical steroids are the most commonly prescribed drugs in dermatology. They are indicated in a variety of conditions such as psoriasis, atopic dermatitis, seborrheic dermatitis, intertrigo, eczema, and lichen simplex chronicus due to their anti-inflammatory, immunosuppressive, and anti-mitogenic effects.[ 1 ] Long-term use of topical steroids is associated with numerous side effects which are both topical and systemic. Locally, they cause atrophic changes in the skin such as striae, telangiectasia, stellate pseudoscars, hypopigmentation, fragile skin, ulceration, purpura, impaired wound healing, and facial hypertrichosis.[ 2 ] Moreover, topical steroids can increase local susceptibility to bacterial, fungal, and viral infections. To minimize the side effects of topical steroids; potency, delivery vehicle, frequency of administration, and site of application should be considered before prescribing.[ 3 ] Topical steroids are misused for skin infections, acne, and also as fairness creams. Young adults procure topical steroids over the counter and use them for a subjective feeling of better appearance. A study reported that more than half of the prescriptions of topical steroids were delivered for fungal infection. Availability over the counter, self-medication by patients, affordability, and poor health infrastructure make topical steroids one of the most commonly misused medications among the masses. The misuse is so rampant that a major proportion of dermatology-related clinical visits by patients is for complaints concerning the adverse effects related to excessive usage of topical steroids.[ 4 ]

There is a need to assess the practices regarding the use of topical steroids. Studies concerning steroid abuse have been reported from multiple countries including China,[ 5 ] Iraq,[ 6 ] and the USA[ 7 ] but the evidence is limited from Indian studies.[ 8 ] Owing to the growing menace of topical steroid abuse, there is a need to assess the awareness among masses regarding knowledge pertaining to the use of topical steroids. There have been no studies in India assessing the knowledge of the people regarding topical steroid use. Moreover, across the world too, very few studies have been conducted pertaining to this aspect.[ 9 , 10 , 11 ]

This study was conceptualized to assess knowledge and practices regarding the use of topical steroids and to analyze the prescription containing topical steroids in patients visiting dermatology clinic. The study also compared the awareness and practices of patients being prescribed topical steroids within the dermatology out-patient department (OPD) of the tertiary care hospital, to those reporting to the OPD with steroids prescribed from outside.

Subjects and Methods

This was an observational, cross-sectional study conducted in the dermatology OPD in a tertiary care hospital. It was initiated after obtaining permission from the institutional ethics committee (EC/148/2016) in January 2017 and was registered in the clinical trials registry of India. (CTRI No: CTRI/2017/12/010733) The study has been performed in accordance with Indian Good Clinical Practices and the Indian Council of Medical Research guidelines. Patients of either gender between the age group of 18 to 65 years, visiting dermatology OPD of tertiary care hospital receiving topical steroids continuously or intermittently for a period of at least 1 week or more were included after obtaining written informed consent. They were enrolled in the study over a period of 12 months from February 2017 to January 2018. The patients were enrolled as they attended the dermatology clinic (convenient sample) and formal sample size calculation was not done. The patients were divided on the basis of their initial prescription of topical steroids into institutionally prescribed (those who were initiated on topical steroid treatment in the tertiary care OPD) and externally prescribed (those reporting to the OPD with topical steroids initiated from outside) steroids. A pre-validated questionnaire was administered to the patients. The questionnaire contained 19 questions divided in two domains viz knowledge (type of drug prescribed, indication, side effects, and need for prescription) and practices domain (duration and pattern of use, type of prescriber, frequency of application, quantity of application, relief of symptoms, relapse, abrupt stoppage of drug, use of old prescriptions, over the counter purchase, side effects, and instructions regarding application). Demographic details, type of steroid received, duration prescribed, frequency, indication, and duration were noted down from the prescriptions. Side effects occurring due to the topical steroids were also asked and recorded.

Validation of the questionnaire was performed before administering the questionnaire to the participants. Face validity and content validity was done by ten experts. Face validity was done to assess the clarity of the wording, layout and style, and readability of the questions. For content validity, the experts were asked to rate the questions as essential, useful and nonessential. Content validity ratio [CVR] was calculated based on the ratings by the formula CVR = (n- N/2) ÷ N/2 [where ”n” = Number of experts who found the question essential/useful and ”N”= Total number of experts]. Test to check internal consistency for reliability was done.

Chi-square test was used to compare attributes such as knowledge of the drug, indications, need for a prescription, awareness about side effects, abrupt stoppage of topical steroids, use of old prescriptions, over the counter purchase of topical steroids, and side effects between externally prescribed and institutional patients. The prescription analysis data was analyzed using descriptive statistics. Level of significance was set at P < 0.05. Data analysis was done using SPSS for Windows, Version 16.0. Chicago, SPSS Inc.

A total of 400 patients were included in the study. Mean age of patients was 36.64 ± 12.73 years. The total number of male patients was 243 whereas females were 157. Out of 400, 167 patients were prescribed topical steroids from outside whereas 233 comprised the institutional patients. There were 20 questions in the questionnaire; out of which 19, with a CVR greater than or equal to 0.8 were retained. Internal consistency for the reliability value of Cronbach's alpha for the questionnaire was calculated to be 0.71.

Table 1 depicts responses to the knowledge domain of the questionnaire. Out of 400 patients, 5.5% of patients knew about the type of drug prescribed. When asked about the indication for prescription, 68.75% were not aware of the same. Knowledge regarding side effects of topical steroids was found to be lacking with only 5.6% people knowing that steroids use was associated with side effects. Moreover, 66.25% of the patients did not know that procuring topical steroids required a prescription. The comparison between two patient groups showed that the knowledge regarding the type of drug, indications, and need for prescription was significantly better in the institutional patients as compared to the externally prescribed group ( P < 0.05). However, awareness regarding side effects was missing in both groups.

Analysis of favourable responses to the knowledge domain of the questionnaire

Statistical analysis was done using Chi-square test, P <0.05 was considered significant*

Out of all 400 patients, 77.25% patients reported relief. The earliest symptom to be relieved was itching followed by redness. In acute conditions, duration of symptom relief was observed to be within 3 days. Chronic conditions such as psoriasis required 2 weeks to 3 months. The findings related to practices domain have been presented in Table 2 . Symptom relapse after stopping the medication was observed in 32% of patients. Around 52% of patients receiving steroids for tinea reported relapse of symptoms immediately after stopping the use of the steroid. Out of 400 patients, 96 patients reported experiencing side effects following application of topical steroids and 71% (68/96) were from the externally prescribed group. The most common side effects i.e., exacerbation of lesions; was reported by patients using topical steroids for tinea. Other side effects were hypopigmentation, atrophy, acne, and steroid-dependent red face syndrome. Fifty-nine patients reported that they were provided inadequate instructions regarding the application of topical steroids. Out of these, 7 were not given clear instructions regarding the frequency of application and 52 were not told about the quantity and manner in which topical steroids were to be applied.

Analysis of favourable responses to practices domain of the questionnaire

The data of both groups for the variables duration and frequency has been represented in a combined manner. Out of 400 patients, 135 had been using topical steroids for more than 6 months. The results for the duration of use have been given in Figure 1 .

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Duration of use of topical steroids

Regarding the pattern of use, 292 (of 400) patients said they use steroids continuously and 108 patients reported intermittent use of steroids. Among the externally prescribed patients, only 43.1% (72/167) had been prescribed by dermatologists. The distribution regarding prescribers has been given in Figure 2 .

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Type of prescriber

Among the 400 patients, 159 reported once-daily application, 224 reported twice daily application whereas the remaining 17 reported thrice daily application of topical steroids. The quantification of drug applied was difficult to perform as the finger-tip unit was not used in clinical practice by prescribers. Hence, it could not be evaluated.

Clobetasol was the most common steroid prescribed accounting for 50.75% of the prescriptions, followed by mometasone (25%), fluticasone (13.75%), betamethasone (5%), halobetasol (3.75%), beclomethasone (1.25%), and fluocinolone (0.75%).

Psoriasis was the most common indication for which steroid was prescribed followed by tinea. All the patients who were prescribed steroids for tinea belonged to the externally prescribed group. The distribution of indications has been represented in Figure 3 . Other indications included acne (4), melasma (3), scabies (1), alopecia (1), and acanthosis (1) in the externally prescribed group and contact dermatitis (4), Prurigo nodularis (2), and atopic dermatitis (2) in the institutional group.

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Indications for prescription of topical steroids

Out of 400 patients, 191 received steroid fixed-dose combinations (FDC) [ Figure 4 ]. The most commonly prescribed formulations of topical steroids were creams in 310 patients followed by ointments (80) and lotions (10). Ultrahigh potency steroids were prescribed to 234 patients, moderate-to-potent steroids to 146 patients whereas 20 patients received low-potency steroids.

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Fixed-dose combinations containing topical steroids

Steroid abuse has become a growing concern amounting to a large proportion of dermatology clinic visits. The analysis of the questionnaire in this study revealed a lack of knowledge in terms of the type of drug being used by the patients and the indication for using the same. Only 5.5% of patients were aware that they were using a topical steroid. Moreover, more than half of the patients were not even aware of the indication for which they were being prescribed the medication. Less than 6% knew that steroid use is associated with side effects. The steroids in some cases had been either self-prescribed or prescribed by friends or family. The practices followed regarding the use of steroids highlighted the extent of misuse in the community. The glaring finding was that tinea was a common indication for using topical steroids in the community. Despite the heavy patient load, institutional practices were found to be better than those of the externally prescribed patients.

A major concern for dermatologists in recent years has been unscrupulous selling by chemists without prescriptions. Our study revealed that more than one-third of the patients had obtained topical steroids without a prescription while close to one-eighth had reused old prescriptions. Over the counter use of topical steroids was significantly higher in the externally prescribed patients, compared to the institutionally prescribed patients since they were not aware of the need for a prescription to procure steroids. Sinha et al . reported that 80% of people had obtained steroids over the counter while only 4% had consulted dermatologists.[ 12 ] Balasubramanian et al . also reported a high prevalence of over the counter use of topical steroids.[ 13 ]

Out of all the topical steroids, only clobetasol propionate, clobetasone 17-butyrate, fluticasone propionate, and mometasone furoate were included in Schedule H. The remaining have not been mentioned. A note at the bottom of this list states that topically applied drugs do not come under the category of Schedule H. This creates confusion leading to difficulty in interpretation of the data from Schedule H.[ 14 ] Therefore, there is a need to have better clarity on the prescription category of topical steroids in Schedule H.

Topical steroids or steroid-containing antifungal creams are commonly misused for fungal infections particularly in developing countries like India owing to their unregulated sales. Topical steroids may alleviate the symptoms such as itching but do not eliminate the fungus from the skin surface and also leads to antifungal drug resistance.[ 15 ] In our study, among the externally prescribed, the commonest indication for the use of topical steroids was tinea. These patients reported relapse of lesions after few days of steroid application which occurs due to continuous fungal proliferation. Besides, some patients developed tinea incognito and acne. Mahar et al .[ 16 ] also reported fungal infections to be the most common cause for the use of topical steroids followed by acne and skin lightening.

The most commonly prescribed steroid in our study was clobetasol (ultrahigh potency) followed by mometasone cream (moderate potency). A study revealed that four of the five top-selling creams across all segments in India contained clobetasol propionate.[ 17 ] Our study showed that more than half the patients had been using ultrahigh potency steroids whereas the rest used moderate-to-high potency steroids. More than half of the externally prescribed patients received ultrahigh potency steroids for tinea. In the study by Mishra et al .,[ 18 ] patients prescribed potent steroids by non-dermatologists suffered more adverse reactions than those prescribed by dermatologists. The authors attributed this to the lack of knowledge about potency and indications for using steroids, on the part of non-dermatologists. In our study, it was observed that of all the patients prescribed topical steroids for tinea, 60% had been prescribed by general practitioners. This shows that probably these physicians were prescribing steroids even in case of unclear diagnosis, contributing to the steroid misuse. Nagesh et al .,[ 8 ] reported that almost half the patients in their study were advised to use topical steroids by pharmacists, friends, and relatives. The authors claimed that most of the time, general practitioners and doctors from alternative medicine had prescribed these medicines. Our observations are in accordance with these findings.

Our study also showed ultrahigh potency steroids being prescribed by general practitioners, for conditions like tinea. Recently, there has also been a misleading trend to use steroids of mid and strong potency for beautification and in the form of fairness creams. Studies have reported irrational use of steroids for fairness and melasma,[ 19 , 20 , 21 , 22 ] although lesser use for these indications was observed in our study.

According to a study, the total annual sale of steroid creams in India is USD$329 million. Furthermore, 87% of the topical steroid sales were in the form of FDC's. Of these, 70% FDCs contained a topical steroid and antifungal.[ 17 ] Our study supports these findings as we observed that 47.75% of prescriptions contained FDCs. According to our study, the most common FDC used was salicylic acid with steroid, which is a rational indication for use. The most common FDC according to Verma et al . is clobetasol propionate, ornidazole, ofloxacin, and terbinafine,[ 14 ] which was same as the most common antimicrobial-steroid combination used in our study. The Drug Controller General of India (DCGI) and Ministry of Health and Family Welfare of the Government of India had issued through a gazette notification in 2016, that certain fixed-dose combinations (FDC) of topical steroids along with antibiotics drugs had no therapeutic justification and prohibited their manufacture with immediate effect.[ 23 ] As per the recent Central Drugs Standard Control Organization (CDSCO) notification of 2018, among 328 FDCs which have been banned by the DCGI, there are 12 topical steroid FDCs along with antibiotics which have been banned.[ 24 ] We found that one of these (clobetasol propionate, ornidazole, ofloxacin, and terbinafine) was commonly used by externally prescribed patients in our study for tinea. Institutional prescribing practices were found to be better as none of the patients was given topical steroids or FDCs for tinea or in absence of valid indications.

In our study, 24% of the patients reported adverse effects due to steroids. The institutional patients reported significantly lesser side effects compared to the externally prescribed group. The study by Nagesh et al .,[ 8 ] reported side effects in more than half the patients using topical steroids. The knowledge regarding side effects associated with the use of steroids was lacking in both the groups of patients in our study. Our study revealed the practice of abrupt stoppage of steroids by patients after their symptoms got relieved. The practice was significantly higher in the externally prescribed patients. These observations highlight the need to improve awareness of patients, as it is one of the important contributing reasons for steroid misuse.

The misuse of topical steroids in the community is increasing and steps need to be taken at every level to curb the problem. The precautions to be taken while using steroids and practices of using steroids were poor among externally prescribed patients as compared to institutional patients. The fact that 57% of externally prescribed prescriptions were by non-dermatologists might have contributed to the inadequate information being given to the patients. The comparison of prevailing in-house practices with prescriptions from the community helped us to give specific recommendations to our dermatology department.

There have been efforts at a national level by Indian Association of Dermatologists, Venereologists and Leprologists (IADVL). A Taskforce Against Topical Steroid Abuse (ITATSA) by IADVL has submitted an online petition to the Ministry of Health and Family Welfare, Government of India, and CDSCO to look into the issues related to the indiscriminate over the counter sale of topical steroids in India.[ 24 ]

Conclusions

The present study highlights the extent of misuse of topical steroids in the community especially with respect to fungal infections and also indicates an overall lack of awareness about the type of drug and side effects.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for their clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Conflicts of interest.

There are no conflicts of interest.

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