Synthetic AAS are synthetic derivatives of testosterone, showing chemical structures similar to natural steroids. The differences artificially set condition the properties and characteristics of these substances (absorption rate, catabolism, and action). From a sports point of view, it is ideal that the substances used have moderate androgenic and virilizing effects, and elevated anabolic effects [12]. Please note this is important when selecting a steroid.

To determine the steroid’s effects, we must know the therapeutic index, which is the relation between the anabolic (A) and virilizing (V) effect, despite the fact that complete dissociation of the AAS’s androgenic and anabolic effects is not possible [13, 14]. When this index is equal to 1, A and V have the same values. When the index is between 1 and 2, products are strongly virilizing and anabolic, while higher values (3 and 4) are associated with anabolic products. However, values higher than 5 correspond to high anabolic products with low virilizing power.

The development of AAS compounds was originally clinically used for treatment of delayed puberty in men and for growth promotion [15]. The road to establishing AAS’s precise chemical and functional characteristics was long and full of interesting anecdotes before reaching clinical and sportive uses.

To study the origin of AAS, it becomes necessary to start with the studies performed in the nineteenth century, referencing the studies by Berthold, Brown-Séquard, Zoth, and Pregl. Berthold et al. focused their research on the study of the role of the gonads in the development of the human secondary sexual characteristics. It was in 1849 when he performed what is known as the first formal experiment in endocrinology in history. In this study, he described general rooster atrophy after castration, leading to disappearance of aggressiveness and interest in hens. Brown-Séquard presented in the Society of Biology of Paris a controversial scientific report (Elixir of life, 1889) in which he described how he himself had undergone a really peculiar treatment . The procedure consisted of injecting certain doses of three different preparations that he created. Initially, he administered blood doses from testicular veins, subsequently sperm, and lastly an extract from dog and/or guinea pig testes. As suggested by this author, this curious treatment assured physical and mental improvements [16]. By the end of the century, Oskar Zoth and Fritz Pregl, pioneers of exercise physiology, indicated that extracts similar to those proposed by Brown-Séquard (bull testicular extracts) might increase muscular strength in humans [17]. Zoth, some years later awarded the Nobel Prize in medicine, pointed out in his work that “the training of athletes provides an opportunity for further research in this area for a practical evaluation of our experimental results” (in the German original: “Das Training von Sportlern bietet eine Gelegenheit für weitere Forschungsarbeiten in diesem Bereich und für eine praktische Beurteilung unserer experimentellen Ergebnisse”) [15, 18]. Undoubtedly, this statement represents the origin of what the use of steroids will become in the future of sports.

Eugen Steinach, three times nominated for the Nobel Prize in Physiology, performed numerous experiments on animals’ sex change. He suggested a surprising surgical treatment for sperm autotransfusion into the circulatory system in order to rejuvenate male subjects [19]. The surgical manipulation of the human or animal male genitals had already been described by the scientist Voronoff in his book Rejuvenation by Grafting [20]. This controversial Russian researcher prepared his self-supply to use it in his patients and investigations. His first official transplant was performed in 1920 by introducing thin slices (a few-millimeters thick) of chimpanzee and baboon testes in the scrotum of a patient, with the hope that both tissues eventually merged [21].

A few years later, Pezard and Caridroit [22] and Funk and Harrow [23] focused their investigations on understanding the reasons why testicular extracts or other organs and animal anatomical structures (i.e., cockscomb) provoked functional changes in the male reproductive system and/or secondary sex organs. The authors concluded that there should be a substance carried in the blood that might regulate the functioning of these organs. Starling [24] called this substance “hormones.” Subsequently, Pezard and Caridroit called it “testicular hormone.” Funk and Harrow [23] located this substance in men’s urine and named it male hormone.

Some authors designated these years as The Golden Age of Steroid Chemistry [25]. Adolf Butenandt, awarded the Nobel Prize in Chemistry for studying sexual hormones, furthered his studies on the analysis of more than 15,000 l of human urine, thus determining the chemical composition of androsterone [26]. His studies on sex hormones helped the work group of Ruzicka [27], in Ciba laboratories, to establish that the chemical structure of testosterone was very similar to cholesterol. His laboratory became the world reference center for organic chemistry at that time. In later decades, the Organon Company, in which Ruzicka participated from the beginning, introduced many drugs that became very popular in the sports community (Deca-Durabolin, Durabolin, Sustanon 250, and Pregnyl).

The name testosterone comes from the studies performed by Butenandt and Hanisch [28], Ruzicka and Wettstein [29], and David et al. [30]. The chemical structure was firmly established in previous years by David and colleagues when oxidizing testosterone to obtain androstan-4-ene-3,17-dione.

The clinical application of these substances goes back to the 1940s for the treatment of chronic debilitating illness, trauma, burns, surgery, and radiation therapy [31]. In the first scientific article published on testosterone in 1939, the author specifically described the beneficial effects of the use of sex hormones in sports performance [32]. Presumably, during this period, and even before, athletes and researchers had already been using steroids.

Brenton Huggins, an American surgical specialist in prostate cancer, showed that blocking testosterone production may decrease prostate cancer progression, thus reducing its symptoms. He was the first scientist who suggested chemotherapy as a therapy against cancer. He was awarded the Nobel Prize in 1966 [33]. On his part, the biologist Paul de Kruif promoted testosterone to reduce the symptoms of aging by claiming that this hormone increases libido, builds muscles, and sharpens intelligence. Paul de Kruif was maybe the first author to address a historical compilation of studies of testosterone by describing scientific experiences by authors such as Hammond, Werner, and Lalouche.

With the advent of World War II, works stopped or at least we do not have accurate documentation of the line of studies and objectives followed by researchers. Apparently, AAS were used by German scientists during this military confrontation to increase the soldiers’ strength, courage, and aggressiveness [34, 35]. It was not until after World War II that studies on steroids resumed in veterinary and human medicine and sports. There is some evidence that once the conflict was over, the American and Soviet intelligence services seized steroids-relevant information from the captured Nazi scientists. These skills were quickly transferred to the sports field as one more tool in what some years later came to be named the Cold War between the Western and Eastern blocks.

In the mid-1950s, the study of effect of androgens on protein synthesis became accelerated. At the same time, many analogues of testosterone (synthetic steroids), nandrolone, and dihydrotestosterone were developed to obtain a purely anabolic drug. This knowledge meant at that time a topic of special interest to pharmaceutical companies, coaches, athletes, and sports physicians, especially those linked to strength sports.

Despite the fact that some contradictory work reducing the sport advantages of AAS can be found in specialized bibliography, different published reviews and meta-analyses show that AAS users are clearly benefited by enhanced performance. In any case, it is a fact that research in this field is under condition of different aspects (small simple size, use of more than one drug or substance to enhance or counteract steroid effects, impossibility of carrying out double-blind placebo-controlled studies, and that dosage used in studies is often far lower than the self-administered levels for ethical reasons). These circumstances avoid the development of appropriate protocols in humans to understand the daily reality in sports [36].

It must be taken into account that performance improvements change individually (depending on sex and age) and are strongly influenced by aspects such as the dose (physiological, supraphysiological, or abuse dose) and the form of utilization (stacking or cycles of steroid administration).

Steroids became popular in the sports field since the 1950s. In that decade, American and Soviet weightlifters and sportsmen undergoing large amounts of resistance training started using these substances [37]. However, the first documented case of steroid use in sports took place in horse racing in 1941.Some sources indicate that German athletes were the first to use steroids [34].

After World War II, Soviets developed a systematic doping program by taking profit of knowledge from the German scientists who were captured after the war. The intention was to use these substances in the development of Soviet sports teams and, thus, to use their success as propaganda for their political ideology. Recall that the USSR returned to international competition at the Olympic Games of Helsinki (1952). In this period, androgenic steroids occupied an important place. Without doubt, the massive occurrence of steroids altered the normal evolution of the records, thus modifying the results in all the strength sports. Final implementation of steroids in sports took place in the 1960s [38].

Possibly, if athletes who use AAS knew exactly all the possible risks they face, they would avoid its use. These risks are minimized by some athletes, their coaches, and doctors, sometimes in a quite irresponsible and self-interested manner. They are more interested in the benefits than in the potential risks [60]. However, these substances have diverse adverse secondary effects, which are highly dangerous and sometimes not completely known. For this reason, the use of AAS increases the athlete’s risk, especially when doses are not controlled or individualized to what each subject can tolerate without risk to their integrity.

The adverse effects are linked to behavioral changes (mood swings, aggressive behavior, depression, psychosis, addiction, withdrawal, and dependency disorders) [61, 62], thus altering numerous organs and systems [36, 48]. The latter include musculoskeletal system, endocrine system, larynx, urinary system, immune system, alopecia (male pattern baldness), liver (cholestasis, peliosis, hepatoadenoma, hepatocarcinoma), cardiovascular system (hypertension, thrombosis, decreased high-density lipoprotein (HDL) cholesterol, increased cholesterol), female reproductive system (menstrual irregularities, clitoral hypertrophy, uterine atrophy, breast atrophy, teratogenicity), and the male reproductive system.

Infertility may be defined as the inability to conceive after reasonable time (12–24 months) of adequate sexual intercourse without contraceptive measures [63]. This anomaly has been associated with different genetic and nongenetic conditions (hypogonadotrophic hypogonadism, testicular maldescence, structural abnormalities of the male genital tract, genital infections, previous scrotal or inguinal surgery, varicoceles, chronic illness, medication, and exposure to chemicals) [64]. While infertility is a functional impairment that neither compromises the individual’s physical integrity nor threatens his life, it may have important psychological effects.

Some studies reported the relevance and effects of physical exercise on reproductive function [65–75]. Certain sports activities (i.e., cycling and bodybuilding), their training (i.e., high volume and intensity), and associated elements (i.e., steroid issues) may also adversely affect the reproductive system, thus sometimes compromise their fertility . A prolonged and excessive training (high volume, high intensity, and low recovery) carries an overreaching/overtraining status that negatively affects the body and causes changes that affect the endocrine system at the hypothalamic–pituitary–sympathetic adrenal and the HPG axis [68, 76, 77] (discussed elsewhere in this volume Chapter 7).

Along with the training load, some collateral aspects related to sports can also be linked to male infertility : significant alterations of body mass [78], inadequate caloric intake [79], lack of appropriate intake of macro- and micronutrients in the diet [80], high physical and physiological stress [79], oxidative stress [81], alteration of the balance of energy intake [82], reproductive function [83], and possible testicular microtrauma [84]. Among these collateral aspects, we must include the use of the AAS, which, by itself, may exert the most detrimental consequences on fertility .

The main adverse effects of the AAS on the male reproductive system include: