ReviewLong-term psychiatric and medical consequences of anabolic–androgenic steroid abuse: A looming public health concern?
Introduction
The anabolic–androgenic steroids (AAS) are a family of hormones that includes the natural male hormone testosterone, together with its many synthetic relatives (Pope and Brower, 2005), all of which exhibit both anabolic (“muscle building”) and androgenic (“masculinizing”) properties (Kopera, 1985, Sheffield-Moore and Urban, 2004). AAS should not be confused with other types of steroids such as corticosteroids (e.g., cortisone or prednisone), which have no anabolic effects and hence little abuse potential (Pope and Brower, 2005, Sheffield-Moore and Urban, 2004). When taken in supraphysiologic doses, AAS allow users to greatly increase muscle strength and athletic performance, often well beyond the limit attainable by natural means (Kouri et al., 1995). As a result, many elite competitive athletes have used AAS—and this phenomenon has recently generated much publicity, as evidenced by burgeoning media reports around the world (Ewing, 2008, Fainaru-Wada and Williams, 2006, Magnay, 2008, Swartz, 2007) and recent investigations by the United States Congress (110th United States Congress, 2005; Mitchell, 2007). The great majority of illicit AAS users, however, are not elite athletes; indeed many are not competitive athletes at all, but simply individuals who want to become more muscular (Buckley et al., 1988, Kanayama et al., 2001b, Parkinson and Evans, 2006).
This much larger population of ordinary AAS abusers started to grow in the late 1970s and early 1980s (as detailed below), but has remained less visible than most other populations of substance abusers, because AAS users rarely seek treatment (Pope and Brower, 2008), rarely come to the attention of physicians in general (Dawson, 2001, Kutscher et al., 2002), and frequently distrust physicians (Pope et al., 2004). Field studies of these illicit users show that they commonly take two or more AAS simultaneously (a practice known as “stacking”), often ingesting a total AAS dose equivalent to 600–1000 mg of testosterone per week, and sometimes even 3000–5000 mg per week (Fudala et al., 2003, Parkinson and Evans, 2006, Parrott et al., 1994, Pope and Katz, 1988, Pope and Katz, 1994, Wilson-Fearon and Parrott, 1999). These latter doses are 50–100 times greater than the natural weekly production of testosterone by the normal male testis (Reyes-Fuentes and Veldhuis, 1993). Illicit users typically take AAS in repeated courses, or “cycles,” each lasting several weeks to several months (Pope and Katz, 1988), sometimes adding up to several years of cumulative lifetime exposure (Kanayama et al., 2006, Kanayama et al., 2003b, Parkinson and Evans, 2006).
Over the last 20–30 years, illicit AAS use has grown into a widespread substance abuse problem in the United States (Buckley et al., 1988, Johnston et al., 2006, McCabe et al., 2007, Yesalis et al., 1993) and many other countries (Galduroz et al., 2005, Handelsman and Gupta, 1997, Melia et al., 1996, Nilsson et al., 2001, Pallesen et al., 2006, Rachon et al., 2006, Wanjek et al., 2007). Most individuals with current or past AAS use are young men (Brower, 2002, Kutscher et al., 2002, Pope and Brower, 2005), but some – especially those who first started AAS in the 1980s – are now reaching middle age. Although many of these older men no longer use AAS, accumulating evidence suggests that they may still be vulnerable to long-term psychiatric and medical effects from their former drug use. In this paper, we suggest that these effects may pose a growing public health concern, as large numbers of these men move into middle age and beyond. As a foundation for this discussion, we begin with a more detailed chronology of the AAS epidemic, illustrated in Fig. 1, and explained in the following paragraphs.
Section snippets
The evolution of the problem
Testosterone was first isolated in the 1930s (David et al., 1935, Wettstein, 1935); synthetic derivatives of testosterone quickly followed, and both testosterone and other AAS were widely applied for medical and psychiatric purposes by the end of the following decade (Altschule and Tillotson, 1948, Gribetz et al., 1955). It was not until the 1950s, however, that athletes began to discover that AAS could greatly increase their muscularity. AAS were apparently first used by the Russians at the
Cardiovascular effects
Supraphysiologic doses of AAS appear to produce a range of adverse cardiovascular effects, including hypertension (Kuipers et al., 1991, Lenders et al., 1988, Urhausen et al., 2004), cardiomyopathy (Ferenchick, 1991b, Stolt et al., 1999, Sullivan et al., 1999, Vogt et al., 2002), left ventricular hypertrophy (Payne et al., 2004, Urhausen et al., 2004), dyslipidemia (increased low-density lipoprotein and decreased high-density lipoprotein cholesterol, with potential acceleration of
The prevalence of adverse effects in long-term AAS users
Little is known about the lifetime prevalence of the various medical and psychiatric consequences of AAS use described above. It might be speculated that publication bias exaggerates the apparent magnitude of AAS-associated pathology, in that rare cases of cardiac or hepatic toxicity, or of psychiatric effects such as violence or suicide, find their way into published case reports, while the great majority of long-term illicit AAS users are healthy. Indeed, some authors have suggested that
Conclusions
Accumulating evidence suggests that long-term use of supraphysiologic doses of AAS may have adverse effects on a number of organ systems, leading to both medical and psychiatric pathology. Importantly, accumulating evidence suggests that some of these effects may persist long after last AAS exposure. However, the frequency and severity of AAS-induced morbidity and mortality is still poorly understood, largely because these effects may not declare themselves until users enter middle or old
Conflicts of interest
Dr. Pope has provided expert testimony in legal cases involving anabolic steroids on two occasions in the last 3 years. Doctors Kanayama and Hudson report no conflicts of interest.
Acknowledgements
This work was supported in part by NIDA grant DA016744 (Drs. Kanayama, Hudson, and Pope).
Funding. Funding for this study was provided by NIDA Grant DA016744; NIDA had no further role in the design or writing of this review or in the decision to submit the review for publication.
Contributors. Authors Kanayama and Pope performed the literature searches, analysis of studies, and initial drafting of the manuscript. Author Hudson critiqued the initial draft and contributed to all subsequent
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