Mean body mass index (BMI) was 34.7 kg/m2, with all but one of the patients having a BMI of ≥30 kg/m2. All patients presented with proteinuria (mean 10.1 g/d; range 1.3–26.3 g/d) and all but one presented with elevated serum creatinine levels (mean 265.3 μmol/L (3.0 mg/dL); range 115.0–689.7 μmol/L (1.3–7.8 mg/dL)). If the increase indeed is causal, it remains to be determined whether this reflects a true decrease in GFR or whether AAS affect serum cystatin C concentrations by other means. Unfortunately, because of its cross-sectional setup, this study does not allow to infer causality. Almost all of them had Simon grade 1 gynecomastia, with one subject progressing from Simon grade 2 at the end of the AAS cycle to grade 3 three months after the cycle, presumably due to the hypogonadal state that followed after cessation of use. A variety of conditions that affect the levels or actions of these sex hormones can therefore cause gynecomastia. The condition remains prevalent throughout adulthood, with one study reporting gynecomastia in 40.5% of healthy young men aged 18–26 years (199) and another reporting detectable palpable breast tissue in 36% of healthy adult men aged 16–58 years (200). While these drugs are commonly already acquired by AAS users from the black market, they might be prescribed to patients suffering from erectile dysfunction which is either organic or psychogenic in nature. Side effects include headache, flushing, dyspepsia, nasal congestion, dizziness, transient abnormal vision and cyanopsia (specific to sildenafil), and back pain and myalgia (specific to tadalafil) (196). Some AAS users self-medicate with phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil to counteract erectile dysfunction (65). Natural AAS like testosterone and DHT and synthetic AAS are analogues and are very similar structurally. Aromatase is highly expressed in adipose tissue and the brain, and is also expressed significantly in skeletal muscle. 5α-reductase is widely distributed throughout the body, and is concentrated to various extents in skin (particularly the scalp, face, and genital areas), prostate, seminal vesicles, liver, and the brain. In addition, DHT is metabolized by 3α-hydroxysteroid dehydrogenase (3α-HSD) and 3β-hydroxysteroid dehydrogenase (3β-HSD) into 3α-androstanediol and 3β-androstanediol, respectively, which are metabolites with little or no AR affinity. It is the most frequent adverse event in older men receiving testosterone replacement therapy (TRT) (40). Classification of a side effects’ probability is based on expert opinion of the authors. What follows is an overview of the most important or frequent side effects of AAS use based on the best available evidence from the literature. The clinical effects that originate from these nongenomic actions are unclear and remain to be characterized. Additionally, AAS exert nongenomic effects which, at least in part, appear to be mediated by a receptor different from the AR (31, 32). Once bound to these sites, the complex regulates gene transcription and thereby exerts its various effects. Albuminuria, as measured by dipstick analysis, emerged or increased in 16% of the subjects (155). In the HAARLEM study, a transient small increase in serum creatinine concentrations of unknown clinical relevance was observed during AAS use (from 93.1 μmol/L (1.05 mg/dL) to 97.8 μmol/L (1.11 mg/dL)). Statins might cause muscle pain in a small percentage of users (152), but this side effect might occur more frequently in those who engage in regular intense exercise (153). Although, of course, the AAS user will not necessarily disclose his use of AAS or present with side effects caused by it. With an estimated global lifetime prevalence rate of 3.3% (6.4% for males and 1.6% for females) (2), virtually every practising physician will provide care for an AAS user at some point in their career. Chemical structure of the steroid nucleus consisting of three cyclohexane rings (A–C) and one cyclopentane ring (D). Besides this valid medical use, AAS are widely used – or rather, abused – for their muscle-building and strength-increasing properties in dosages far exceeding those used therapeutically. Extraction of hormones from urines began in China around 100 BCE.citation needed Medical use of testicle extract began in the late 19th century while its effects on strength were still being studied. Use of cow urine for treatment of ascites, heart failure, renal failure and vitiligo has been elaborately described in Sushruta Samhita, suggesting that ancient Indians had some understanding of steroidal properties of cow urine around 6th century BCE. The most commonly employed human physiological specimen for detecting AAS usage is urine, although both blood and hair have been investigated for this purpose. DHT, via its metabolite 3α-androstanediol (produced by 3α-hydroxysteroid dehydrogenase (3α-HSD)), is a neurosteroid that acts via positive allosteric modulation of the GABAA receptor. Aside from prohormones and testosterone undecanoate, almost all orally active AAS are 17α-alkylated. In contrast to most other AAS, 17α-alkylated testosterone derivatives show resistance to metabolism due to steric hindrance and are orally active, though they may be esterified and administered via intramuscular injection as well. The documents stated that 75 wrestlers—roughly 40 percent—had tested positive for drug use since 2006, most commonly for steroids. The World Anti-Doping Agency (WADA) maintains the list of performance-enhancing substances used by many major sports bodies and includes all anabolic agents, which includes all AAS and precursors as well as all hormones and related substances. Norethandrolone was introduced for medical use in 1956, and was quickly followed by numerous similar steroids, for instance nandrolone phenylpropionate in 1959 and stanozolol in 1962. It has been suggested that this may contribute as an alternative or additional mechanism to the neurological and behavioral effects of AAS. In addition, some AAS, such as 19-nortestosterone derivatives like nandrolone, are also potent progestogens, and activation of the progesterone receptor (PR) is antigonadotropic similarly to activation of the AR. These observations suggest that the AR is mainly or exclusively responsible for masculinization and myotrophy caused by androgens. Indeed, DHT has less than 1% of the affinity of testosterone for ZIP9, and the synthetic AAS metribolone and mibolerone are ineffective competitors for the receptor similarly. Moreover, nandrolone is metabolized by 5α-reductase, but unlike the case of testosterone and DHT, the 5α-reduced metabolite of nandrolone has much lower affinity for the AR than does nandrolone itself, and this results in reduced AR activation in 5α-reductase-expressing tissues. For this reason, they have the capacity to bind to and be metabolized by the same steroid-metabolizing enzymes. While the clinical implications of an AAS-induced hematocrit increase are unclear, there is reason to believe it might be detrimental to health. Treating healthy young men with the 5α-reductase inhibitors finasteride and dutasteride for one year had no effect on hemoglobin levels (44). The stimulatory effect on erythropoiesis is dose-dependent – at least beyond 300 mg testosterone enanthate weekly – and is more pronounced in older men (42).
