# Psychological and Behavioral Effects of Endogenous Testosterone Levels and Anabolic



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 1*
*By Michael S. Bahrke, Charles E. Yesalis III, and James E. Wright*

*1. History of Anabolic-Androgenic Steroid Use in Competitive Sports and Medicine*

The primary use of anabolic-androgenic steroids is in replacement therapy for male hypogonadism; other medical uses of anabolic-androgenic steroids include growth promotion in various forms of stunted growth, osteoporosis, mammary carcinoma, anaemias and hereditary angioneurotic oedema. Observation and clinical trials indicate that adjuvant therapy with anabolic-androgenic steroids can be supportive in the treatment of conditions characterised by a negative nitrogen balance: major surgery, cachexia of various origins, burns, traumata, convalescence from illness, injuries and immobilisations, as well as during radiotherapy and therapy with cytotoxic drugs (Kochakian 1976; Kopera 1976, 1985; Kruskemper 1968). Unfortunately, research concerning additional legitimate applications of anabolic-androgenic steroids has most likely been impeded by the existing emotional polarisation of anabolic-androgenic steroid supporters and opponents. As Kochakian (1990) has pointed out, the frequent and often hysterical references in the popular press to unsubstantiated adverse effects of anabolic-androgenic steroids has often resulted in the loss of both media and medical/scientific credibility, deterring research on beneficial and legitimate medical uses, and as a stimulus and encouragement for litigation against physicians.

The use of various physical and chemical aids in performance enhancement is not a novel problem but has been a feature of athletic competition since the beginning of recorded history (Csaky 1972; Strauss & Curry 1987). Ancient Greeks ate sesame seeds, bufotenin was used by the legendary berserkers in Norwegian mythology, and the Andean Indians and the Australian aborigines chewed, respectively, coca leaves and the pituri plant for stimulating and antifatiguing effects (Csaky 1972; Williams 1974). Anabolic steroids have been used by athletes to enhance appearance and performance for many years. The first ergogenic use of anabolic-androgenic steroids was reported to have occurred in the 1950s among weightlifters and bodybuilders (Wright 1978). Since that time their use has permeated a myriad of sports (Anderson & McKeag 1985, 1989; Buckley et al. 1988; Gilbert 1969; Starr 1981; Todd 1987; Wade 1972; Yesalis et al. 1990a). Payne (1979) suggested that the use of anabolic-androgenic steroids was a significant problem at the 1964 Olympic Games. Ljungqvist (1975) reported that one-third of a sample of elite track and field athletes in Sweden; surveyed admitted to systematic anabolic-androgenic steroid use by 1972. Silvester (1973) reported that 68% of a sample interviewed at the 1972 Olympic Games from 7 countries, and who were competing in such diverse activities as throwing, jumping, vaulting, sprinting, and running up to 5000m, admitted having used anabolic-androgenic steroids. Although it was suggested as early as 1973 (Frazier 1973) and reiterated later (Wright 1978, 1980, 1982), it is now evident that the use of anabolic-androgenic steroids is not limited to elite amateur and professional athletes. It has trickled down from the professional and college levels to the high schools and junior high schools (Buckley et al. 1988; Yesalis et al. 1989a, 1990a). The estimated prevalence of nonmedical anabolic-androgenic steroid use and the implications for society and public health have also prompted several scientific meetings, including a technical review at the National Institute on Drug Abuse in 1989, and both federal and state investigations and efforts to reclassify anabolic-androgenic steroids as controlled substances (Government Accounting Office 1989; Halligan et al. 1989; Taylor 1987a,b; Yesalis 1989; Yesalis et al. 1990a) despite nonconcurrence from the American Medical Association (AMA 1989).

Patterns of anabolic-androgenic steroid use among athletes have been determined from several surveys. Burkett and Falduto (1984) interviewed 24 weight-training athletes at a gymnasium in a metropolitan area of the southwestern United States. Subjects surveyed took a combined steroid does of 4 to 8 times the recommended medical does, used more than one anabolic-androgenic steroid at a time (?stacking?), combined use of injectable and oral anabolic-androgenic steroids, and used the drugs frequently, usually in cycles (an episode of use from 6 to 12 weeks or more). Although Burkett and Falduto questioned a very specific sample of anabolic-androgenic steroid users, they concluded that their subjects seemed to be representative of the type of athletes who used anabolic-androgenic steroids. Cohen et al. (1988), in a study of hypercholesterolaemia in 21 male powerlifters using various anabolic-androgenic steroids, reported significantly higher levels of anabolic-androgenic steroid use in their subjects than Burkett and Falduto (1984), with daily dosages ranging from 60 to 400mg. Pope and Katz (1988) have also reported daily dosages between 10 and 200mg (of various anabolic-androgenic steroids) for anabolic-androgenic steroid users in their investigation of affective and psychotic symptoms associated with anabolic-androgenic steroid use.

Frankle et al. (1984) found that 110 of 250 weightlifters they interviewed in several gymnasia in the metropolitan Chicago area, many of whom were noncompetitive lifters, also used a variety of anabolic-androgenic steroids. 50 weightlifters were interviewed in detail; a majority (56%) had no competitive intents in weightlifting, bodybuilding or any other athletic events, a proportion that substantially exceeds that found by Buckley et al. (1988) in a nation-wide survey of male high school seniors. Frankle et al. (1984) concluded that anabolic-androgenic steroid abuse had reached alarming proportions in noncompetitive athletes.

The Buckley et al. (1988) survey suggests that one-quarter to one-half million adolescents in the United States have used or are currently using anabolic-androgenic steroids. Anderson and McKeag (1985) reporting on a nation-wide survey of alcohol and drug use among college athletes indicated that anabolic-androgenic steroids were used in all men?s sports, one women?s sport, and that the sport with the greatest admitted use (9%) was football. The overall anabolic-androgenic steroid use rate in all sports nationally was 4%. Anderson and McKeag (1989) replicated their original study 4 years later and although they found that overall use rates for anabolic-androgenic steroids had remained stable, anabolic-androgenic steroids were now being used in 2 additional women?s sports. A survey and follow-up telephone interview by Yesalis et al. (1988) following the 1987 US Powerlifting Federations? National Championship found 33% of the initial respondents and 55% in a follow-up subsurvey of the same group, admitting previous anabolic-androgenic steroid use. Since athletes may have a propensity to underreport of disguise their actual anabolic-androgenic steroid use for various reasons, caution must be used when interpreting values concerning the prevalence of anabolic-androgenic steroid use by athletes.


----------



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 2*

*2. Potential Mechanisms for Some Anabolic-Androgenic Steroid Effects on the Nervous System*

Anabolic-androgenic steroids have been shown to exert significant effects on both the development and functioning of the nervous system. Androgens were shown to act directly on the brain long ago (Phoenix et al. 1959). These authors suggested that during early development androgens acted to organise neural pathways involved in male behaviours, while during adulthood they acted on differentiated pathways to activate previously organised behaviours. Data from studies of sexual dimorphism in animals clearly demonstrate differences in brain areas in male rats including: a much larger nucleus of the preoptic area (Gorski et al. 1978), a larger mid-portion of the medial amygdaloid nucleus (Nishizuka & Arai 1981), a greater number of motor neurons innervating the bulbocavernosus muscle (Breedlove & Arnold 1980), and a larger superior cervical ganglion (McEwen 1980). This latter testosterone-induced increase in post-ganglionic neuron number has been attributed to the ability of testosterone to increase nerve growth factor (Ishii & Shooter 1975), which in turn enhances neuronal survival (Hendry & Campbell 1976; Levi-Montalcini 1964).

In both rodents and primates androgen receptors are concentrated in the pituitary, hypothalamus, preoptic area, septum, and amygdala (McEwen 1980; Tobet et al. 1985). Androgen receptors in the brain recognise both testosterone and its 5a -reduced metabolite, 5a -dihydrotestosterone (Christensen & Gorski 1978). Many central nervous system and behavioural effects are thought to be produced by aromatisation of androgens to estradiol, which varies from region to region in the brain but is most prominent in the hippocampus, amygdala and preoptic area (McEwen 1980). The roles of aromatisation and 5a -reduction in producing the effects of testosterone in adults are, however, not well studied, particularly with regard to behaviour. Inasmuch as aromatase blockers inhibit testosterone-induced sexual behaviour in male rats (Morali et al. 1977), it seems likely that aromatisation of testosterone to estrogen plays a key role in the facilitation of male sexual behaviour.

Adult male rats eat more and are less active than females (Wade 1976). Castration reduces both eating and activity (Hoskins 1925; Kakolewski et al. 1968; Wang et al. 1925). Low doses of testosterone restore food intake while pharmacological doses reduce it further, a decrease which is blocked by progesterone as is the inhibitory effect of estradiol on feeding, suggesting that the inhibitory effect of high doses is due to aromatisation. 5a -Dihydrotestosterone, which is not aromatisable, increases food intake (Wade 1976). Estradiol, but not 5a -dihydrotestosterone, stimulates locomotion in castrated male rats (Roy & Wade 1975). Antiestrogens attenuate testosterone-induced activity while antiandrogens do not, indicating that aromatisation to estrogen is necessary for enhancement of physical activity (Stern & Murphy 1971). Both testosterone and 5a -dihydrotestosterone thus appear to be responsible for increasing feeding behaviour while aromatisation of testosterone to estrogen is required to increase activity level. Testosterone is known to affect growth hormone secretion (Martin et al. 1968) and plasma somatomedin C (Rosenfield & Furlanetto 1985). In one study of adult athletes self-administrating anabolic-androgenic steroids, but not growth hormone, levels of growth hormone were reported to be 5 to 60 times higher than normal (Alen et al. 1987). Modulation of secretion of growth-promoting, and possibly other, hormones appears to occur via endogenous opiate peptide pathways (Rogol et al. 1990; Veldhuis et al. 1984), probably as a result of the action of the estrogen metabolites of testosterone (Ho et al. 1987). The effects of synthetic anabolic-androgenic steroids, with their prolonged half-lives, and of pharmacological doses are not known, but it is apparent that they or their metabolites can bind to glucocorticoid and progesterone, as well as estrogen, receptors and thus elicit other than purely androgenic effects (Janne 1990).

Data from animal studies indicate that both estrogens and androgens act on neural structures that are identical to or closely associated with sensory pathways and the ventricular recess organs (periventricular gland) of the hypothalamus (Stumpf & Sar 1976). Androgens have been reported to selectively stimulate neurons of the somatomotor system and circuits associated with aggression (Stumpf & Sar 1976). Androgen receptors are located on ? motor neurons (Sar & Stumpf 1977), and play a role in regulating their length in adulthood (Kurz et al. 1986). Androgens also facilitate the release of acetylcholine at the neuromuscular junction of the bulbocavernosus (Vyskocil & Gutmann 1977).

Itil et al. (1974) have demonstrated quantitatively the physiological correlates of certain previously reported behavioural effects of an anabolic-androgenic steroid (mesterolone) such as an increase of mental alertness, mood elevation, improvement of memory and concentration, and reduction of sensations of fatigue, all of which can partly be related to the central nervous system (CNS) ?stimulatory? effects of mesterolone. Electroencephalographic profiles of varying dosages of mesterolone were found to be very similar to those seen with psychostimulants such as dextroamphetamine and the tricyclic antidepressants. Single oral doses as low as 1 mg were shown to affect brain function. Others (Broverman et al. 1968; Klaiber et al. 1967; Stenn et al. 1972) have concluded that the adrenergic-like effects of testosterone on brain function are as a result of an elevation of the brain noradrenaline (norepinephrine) level, which might be the result of the inhibition of brain monamine oxidase (MAO) activity. Further speculation indicates that the ?heightened? state of behavioural reactivity which facilitates the automatisation of behaviour may well be due to an increased level of brain noradrenaline.

Hannan et al. (1988) have examined plasma homovanillic acid changes following 6 weekly intramuscular injections of 100 or 300mg of testosterone enanthate or nandrolone decanoate administration in 25 males and found significant increases in homovanillic acid for both of the nandrolone but neither of the testosterone treatments. Since a large proportion of plasma homovanillic acid originates from CNS metabolism of dopamine, the demonstrated change associated with nandrolone administration confirms an anabolic-androgenic steroid-induced alteration in CNS neurotransmitter metabolism and suggests a mechanism to explain reported altered behaviour in some anabolic-androgenic steroid users. Interestingly in this regard the deletion of the 19-methyl group in nandrolone produces a more planar steroid than testosterone that thus, like 5? -dihydrotestosterone, has altered receptor binding affinities, as well as unique metabolites. It must be added that estrogens are also known to alter central nervous system neurotransmitters through inhibition of monamine oxidase activity, so aromatisation of testosterone to estrogen could also play a role (Klaiber 1972).

Inasmuch as improvements in muscle strength and power can in part be accounted for by neural factors, including neurotransmitter levels (Hakkinen & Komi 1983; Moritani & deVries 1979), findings that androgens may in some manner modify neural and neuromuscular functions support the concept of a significant role for these mechanisms in the production of ergogenic effects (Alen et al. 1984; Brooks 1980; Hakkinen & Alen 1986; Wilson 1988).


----------



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 3*

*3. Plasma Testosterone Levels and Aggression*

*3.1 Testosterone and Aggression in Animals*
Numerous studies have shown relationships between testosterone levels, dominance, and aggressive behaviour in various species of animals (Allee et al. 1939; Barfield et al. 1972; Bouissou 1983; Bouissou & Gaudioso 1982; Hamilton 1938; Kurischko & Oettel 1977; Payne & Swanson 1973; Rose et al. 1971; Simon et al. 1985; Steklis et al. 1985; Svare 1983; van de Poll et al. 1981, 1986; Zumpe & Michael 1985) including nonhuman primates (Joslyn 1973; Rejeski et al. 1988a; Steklis et al. 1985; Zumpe & Michael 1985).

It has been argued by some reviewers that primates are less dependent on androgens for the expression of aggression than ungulates or other animals lower in the evolutionary chain (Bouissou 1983). However, Rejeski et al. (1988a) determined that intramuscular injection of testosterone propionate increased the frequency of aggressive behaviour in monkeys. 10 cynomolgus monkeys were assigned to either an experimental (n=5) or a control group (n=5) and given biweekly injections; the experimental group received testosterone propionate 4 mg/kg, and the controls a sham solution. Prior to and upon completion of an 8-week treatment period, behavioural observations (slapping, grabbing, stare threat, chasing, fleeing, etc.) were conducted. Although the administration of testosterone propionate resulted in a significant increase in aggression, more important was the finding that changes in behaviour were mediated by social status; that is, the incidence of both contact and noncontact aggression in dominant monkeys was far greater than the frequency of these behaviours in subordinate monkeys.

Joslyn (1973) has reported that injecting 3 infant female rhesus monkeys with 2mg of testosterone propionate intramuscularly 3 times per week over 8 months increased their aggressive behaviour so much so that they replaced males in top positions of the social hierarchy. Since this behaviour persisted for a year after the last hormone injection, the author suggests either that the male hormone may have directly induced a permanent change in the nervous system or alternatively that the socially dominant behaviour was so well learned during hormone treatment that it became independent of hormonal support.

Indeed, Bernstein et al. (1974) have evaluated in a series of experiments the converse of this relationship, i.e. the influence of multiple environmental and social variable upon circulating testosterone levels in the male rhesus monkey. Factors shown to significantly influence levels of circulating testosterone included among others, alterations in social rank and ?successful? and ?unsuccessful? agonistic encounters.

In general, these and other studies indicate that the level of testosterone, particularly in the prenatal period, but also during puberty and even in adulthood are important in establishing a biological readiness for normal aggressive behaviour and in facilitating the expression of aggression in ?appropriate? social settings in adult animals. They also indicate that both social factors and learning significantly influence the actual expression of aggression in adulthood (Rada et al. 1976a). However, the extent to which exposure to testosterone or other anabolic-androgenic steroid at any phase of the life cycle, and particularly during adulthood, is related to altered moods and feelings in humans, to the expressions of aggression in humans and even other primates, relative to animals lower in the evolutionary chain, is not well known.

*3.2 Testosterone, Mood and Aggression in Humans*
Relative to the animal literature, fewer studies have assessed the relationship of endogenous or exogenous androgens to aggression or violent behaviour in humans. In general, the relationship is less clear than in animal research for a variety of reasons. First, it is difficult to show that animals, possibly excluding primates, experience emotional states that are qualitatively similar to human experiences such as euphoria, depression, anger and others. Second, the effects of sex hormones vary considerably among individuals as well as species. Consequently, conclusions drawn from animal models must be applied cautiously to humans. Lastly, human subjects cannot be subjected to many of the same stringent controls and manipulations used in animal research. Nevertheless, aggressive behaviour and other feelings of hostility have been demonstrated to be related to endogenous testosterone levels in a number of studies using human subjects.

Testosterone is thought to have an activating effect on human aggressive behaviour. The action of testosterone on the central nervous system apparently contributes to the elevated aggressiveness of males compared to females. However, among males, there is the question of whether the level of testosterone reaching the brain and interacting with receptors determines the level of aggressive feelings and behaviour. Attempts to answer this question have included investigations correlating levels of testosterone with aggressive behaviour in normal and incarcerated males, studies examining men with genetic differences in testosterone production for differences in levels of aggression, and research into the effects on behaviour of administered testosterone and antiandrogenic agents.

*3.2.1 Testosterone Levels and Aggression in Adolescents and Young Athletes*
Susman and associates (1985, 1987a,b) have reported on the relationship between hormone levels (gonadotrophins, gonadal steroids and adrenal androgens) and emotional dispositions and aggressive attributes for young adolescents in several reports. Participants were 9- to 14-year-old boys (n=56) and girls (n=52). Assessments of physical maturation consisted of pubertal staging according to Tanner criteria and serum determinations of luteinising hormone, follicle-stimulating hormone, testosterone, estradiol, dehydroepiandrosterone, dehydroepiandrosterone sulphate, and androstenedione. The psychological measures were the Psychopathology and Emotional Tone subscales from the Offer Self-Image Questionnaire for Adolescents and interview questions to assess interactions with peers. Psychopathology and emotional tone (sad affect) scores were higher for boys with high-for-age adrenal androgens (androstenedione) and lower for boys with high-for-age sex steroids (testosterone). Behavioural manifestations of sexuality, interest in dating, was higher for boys with higher-for-age adrenal androgens. Dating and spending time with friends were higher for boys with high-for-age gonadotrophins. Psychopathology and emotional tone were higher for girls with high-for-age gonadotrophins. The results indicate that high-for-age hormone level or early timing of puberty generally was related to adverse psychological consequences for boys and girls, with relations being stronger for boys than girls. Udry et al. (1985), using self-rating questionnaires describing adolescent pubertal development, sexual motivation, and details of sexual behaviour, found that serum testosterone was a strong predictor of sexual motivation and behaviour (with no additional contribution of other hormones) in a sample of 102 boys in grades 8, 9 and 10. No such relationship, however, could be detected in healthy young adult men (Brown et al. 1978).

Olweus et al. (1980) examined serum testosterone, aggression [Olweus Multi-Faceted Aggression Inventory for boys (Olweus 1973), Olweus Q Inventory (Olweus 1975), Thurstone Temperament Schedule (Thurstone 1950)], physical characteristics (pubertal stage, height, weight, chest circumference, and physical strength) and personality dimensions [Eysenck Personality Questionnaire (Eysenck & Eysenck 1975), Situation-Oriented Questionnaires (Schalling et al. 1975), Multi-Component Anxiety Inventory (Schalling et al. 1975)] in 58 normal, healthy 16-year-old adolescent males and found a significant association between testosterone and self-reports of physical and verbal aggression (Olweus Aggression Inventory, Olweus Q Inventory) mainly reflecting responsiveness to provocation and threat. ?Lack of frustration tolerance? was also significantly related to testosterone levels, but several other aggressive dimensions such as antisocial behaviour and impulsiveness were not significantly correlated with testosterone.

Data from a study designed to examine the relationship between serum testosterone levels and aggressive behaviours in a noncompetitive setting using 14 varsity college male hockey players were reported by Scaramella and Brown (1978). They found a significant positive correlation between only 1 of 7 aggressive items (response to threat) on their own aggression questionnaire and serum testosterone.

While these results appear to support the hypothesis of Elias (1981) that testosterone levels fluctuate with alterations in mood, it must be noted that testosterone levels fluctuate from minute to minute in ?normal? individuals, with the most marked changes occurring during puberty (Doering et al. 1975). The other side of the question of the relationship of testosterone and mood and behaviour and an important consideration, is to what extent aggressive behaviour or successful ?expression? of aggression or nonaggressive success produce higher levels of testosterone.

*3.2.2 Testosterone and Mood in Adult Males*
Persky et al. (1971) determined the plasma testosterone level and testosterone production rate in a group of 18 healthy young men, 15 healthy older men, and 6 hospitalised dysphoric men. A battery of anxiety [IPAT Anxiety Scale (Cattell & Scheier 1963), Multiple Affect Adjective Check List (Zuckerman & Lubin 1965), Manifest Anxiety Scale (Dahlstron & Welsh 1960)], depression [Minnesota Multiphasic Personality Inventory (Dahlstron & Welsh 1960)] and hostility tests [Buss-Durkee Hostility Inventory (BDHI; Buss & Durkee 1957)] were administered simultaneously. In the younger men, production rate of testosterone (determined by the constant infusion method) was found to be significantly correlated with both the sum of the hostility responses (Total Hostility) of the BDHI (r=0.66) and the IPAT Anxiety Scale (r=0.52). A multivariate regression equation was obtained for testosterone production rate using 4 subscale psychological measures of aggression and hostility (BDHI Factors I and II, MAACL-H, and IPAT-Q4) which accounted for 82% of the variance in the production rate of testosterone for the younger but not the older group. In the older men, age was the primary (negative) correlate of production rate. Persky et al. (1971) suggest that aggression and age are both important but opposite correlates of testosterone production.

Brown and Davis (1975) also found a significant correlation of the BDHI subscale of irritability with plasma testosterone level in 15 healthy college males. These authors nevertheless suggested that, although testosterone may be related to feeling angry, the translation of such feelings into behaviour is highly dependent upon other factors and did not occur in any of their subjects based on self-reports of aggressive behaviour.

The association between mood (MAACL, MMPI, BDHI) and testosterone levels in 20, normal young men was also investigated by Doering et al. (1975), who found only a very weak positive relationship (r=0.415, p < 0.10) between affect (BDHI Indirect Aggression Scale) and testosterone. Houser (1979) examined the inter- and intrasubject correlations between testosterone and various measures of behaviour (reaction time, arm-hand steadiness, time estimation), affect (MAACL, Nowlis Mood Adjective Checklist, Gottschalk Verbal Anxiety Scale), and physical discomfort (Moos Menstrual Stress Questionnaire) in 5 young males over a 10-week period and found that there was a general deterioration of central nervous system motor functioning and a decrease in positive affect associated with higher testosterone levels. There was also a general decrease in the level of social and general activity associated with rising testosterone values. As the author suggests, the results of this pilot study are obviously limited by the small sample size and a large intersubject variability.

In contrast to the above studies, Meyer-Bahlburg et al. (1974) in a replication of the Persky et al. Study, with a sample of normal male undergraduate students selected on the basis of 4 BDHI subscales which constitute Buss and Durkee?s factor II, found no significant differences in the blood production rate, plasma levels, or urinary levels of androgens in 5 low-aggression and 6 high-aggression subjects. Monti et al. (1977) likewise failed to find any correlation between aggression (as measured by the BDHI or as derived from observer ratings) and the concentration of circulating testosterone in 101 healthy 20- to 30-year-old males, who displayed a wide range of both testosterone values and BDHI responses.

*3.2.3 Testosterone Levels and Aggression in Prisoners*
Relating testosterone levels to mood, behaviour, and psychological inventories in other populations has been somewhat easier and is no doubt responsible for the seeming consensus that testosterone levels are related to aggression in humans. In 1972, Kreuz and Rose (1972) studied levels of plasma testosterone, fighting and verbal aggression in prison, and past criminal behaviour in 21 young prisoners. Several psychological tests [BDHI, IPAT Anxiety Scale, and Marlow-Crowne Social Desirability Scale (Crowne & Marlow 1960)] were administered. Although plasma testosterone levels, measured over 2 weeks, did not differ in those classified as fighting and nonfighting individuals based upon prison records, the 10 prisoners with histories of more violent and aggressive crimes in adolescence did exhibit significantly higher levels of testosterone than the 11 prisoners without such a history. Unlike Persky et al. (1971), Kreuz and Rose found that, although there were significant correlations among psychological tests, none of the test scales (hostility, anxiety, and social desirability) correlated with plasma testosterone. Nor did any test scales correlate with fighting behaviour. Perhaps the most important contribution of the Kreuz and Rose study is the presentation of the hypothesis that within a population that is predisposed by virtue of social factors to develop antisocial behaviours, levels of testosterone may be an important additional factor (a promoter rather than an initiator) in placing individuals at risk for violent or criminal behaviour.

Ehrenkranz et al. (1974) also examined plasma testosterone levels in 36 male prisoners: 12 with chronic aggressive behaviour, 12 socially dominant without physical aggressiveness, and 12 who were neither physically aggressive nor socially dominant. Subjects were selected from the general inmate population of a large state penal institution and grouped according to the type of aggressivity of their criminal behaviour: aggravated assault and murder; nonviolent crimes such as theft, cheque passing, and drug-related felonies; and level of social dominance. Classification of subjects was based upon agreement of the study?s investigators, the senior prison psychologist, the senior prison administrator, and inmates participating in the study. Although an attempt was made to halt prisoner medications 1 week prior to the study, several subjects continued to use various types of tranquillising drugs, such as a mixture of phenothiazine and barbiturate, and benzodiazepine. A battery of psychological tests including the BDHI was also administered. Both the aggressive and the socially dominant groups had significantly higher mean testosterone levels than the nonaggressive group. The aggressive group also had a significantly higher level of testosterone than the nondominant group, but not the socially dominant group, and higher than the other 2 groups combined. The aggressive group also scored significantly higher than either of the other 2 groups in the total hostility score of the BDHI. Unfortunately, any conclusions must be tentative based upon the use of other drugs, including barbiturates and all other drugs of abuse, which are known to affect the reproductive axis.

Rada et al. (1976b) also found, within imprisoned sex offenders, that a group of 5 violent rapists had significantly higher testosterone levels than 12 child molesters, 47 other ?less violent? rapists, or a control group of 48 healthy male prison employees. The mean BDHI score for all rapists was significantly higher than the mean for normals, but there was no correlation between individual hostility scores and plasma testosterone. Also, there were no significant correlations between age, race or length of incarceration and plasma testosterone level.

As part of a much larger, double-blind, controlled study of sex chromosome anomalies, hormones, and aggressivity in 4591 men, Schiavi et al. (1984) noted a proportionately significant increase in levels of testosterone when subjects were divided into smaller groups of nondelinquents (n=63), delinquents without violent convictions (n=11), and delinquents with violent convictions (n=4). However, the relation between testosterone level and criminal behaviour was not reflected in measures of aggression derived either from psychological interviews or projective tests (Rorschach Test, Word Association Test, Thematic Apperception Test).

*3.3 Relationship of Testosterone to Moods Other Than Aggression*
In a study of serum testosterone levels, social status and mood in male graduate students between the ages of 22 and 35, Mazur and Lamb (1980) reported that changes in testosterone levels did show a relationship to the subject?s moods. Specifically, their results suggest that when a man achieves a ?rise in status through his own efforts? (either graduation form medical school, winning a tennis match, or winning a lottery), and he has an elevation of mood as a result of the achievement, then that person is ?likely? to have a rise in testosterone. A recent study by Tanaka et al. (1989) found that positive mental health [vigour as measured by the Profile of Mood States (POMS) (McNair et al. 1971)] and athletic achievement motivation (challenge to higher goals, ?fighting spirit?, and value athletics as determined by the Taikyo Sports Motivation Inventory) were each significantly correlated with higher levels of plasma testosterone. Elias (1981) has measured levels of circulating cortisol, testosterone and testosterone-binding globulin in 15 male wrestlers in relation to the outcome of wrestling bouts and found that concentrations of cortisol and testosterone increased consistently during wrestling bouts, while levels of testosterone-binding globulin dropped. Winners of competitive matches showed significantly greater increases in both hormones than losers. Although greater effort and/or haemoconcentration in the winners cannot be ruled out as an explanation, these findings are suggestive that humans, like other social mammals, might undergo specific endocrine changes in response to victory or defeat.

*3.4 Testosterone Levels and Stress*
An association between stress and levels of testosterone has been demonstrated in several studies. Kreuz et al. (1972) found plasma testosterone levels in 18 young men attending a military training course were significantly lower during a stressful period when compared with a less stressful phase. Likewise, Aakvaag et al. (1978) studied the effect of physical and psychological stress (a 5-day combat course) on 8 young male military cadets and found a significant and prolonged reduction in plasma testosterone levels. Francis (1981), in examining the relationship between high and low trait psychological stress, serum testosterone and serum cortisol, found males (30 to 55 years), classified as experiencing high psychological stress [State-Trait Anxiety Inventory (Spielberger et al. 1970)], possessed significantly lower testosterone levels than did their low stress counterparts. Morville et al. (1979) have demonstrated reduced testosterone levels following intense physical effort (100km running races) in male endurance athletes. Testosterone levels were also significantly decreased in 5 male athletes participating in a 20-day 1100km foot race (Schurmeyer et al. 1984).

In summary, a pattern of association between plasma testosterone and both subjectively-perceived and observed aggressive behaviour has been revealed in many of the preceding studies. However, the relationships between plasma testosterone and psychometric indices of aggression and hostility have been less consistent. The results of studies in this section are summarised in table I.


----------



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 4*

*4. Anabolic Steroid Therapy and Moods*
Hermann and Beach (1976), in a review of the psychotropic effects of androgens, concluded that ??androgen deficiency appears to cause a slowing down of both physical and mental functions, a reduction in libido and potency, and a tendency towards moodiness and depression. Conversely, androgen excess seems to stimulate physical and mental function, and to induce assertiveness rather than passivity, although the degree to which these people are overtly aggressive is somewhat unclear.? Hermann and Beach also concluded that, ?As yet no work, to our knowledge, has been done on the possible contribution that the reported variations in hormone levels make to the changed behaviour of those who become mentally disordered, nor to their exact role in metabolic changes which are supposed to accompany such illness.? Unfortunately, although a number of studies have been conducted over the intervening years, little can be added to their conclusion at this point in time. This following section summarises research and clinical observations and effects in individuals with androgen deficiencies receiving androgen therapy.

Franchi et al. (1978) reported a marked increase in libido and sexual, physical and/or mental activities in all 34 hypogonadal male patients (18 to 49 years) given testosterone undecanoate (40 to 60 mg/day, orally) for 8 months when compared with a withdrawal period (3 weeks). Unfortunately, no information concerning the questionnaires used to assess the behavioural and mood changes is provided. No side effects were reported by any of the patients throughout the 8 months of therapy.

Franchimont et al. (1978) found improved mental and physical activity at 3-week intervals over 9 weeks in 7 and 2 of 10 hypogonadal male patients (16 to 51 years), respectively, undergoing therapy with oral testosterone undecanoate (120 to 240 mg/day). Again, no information is provided concerning how behavioural and mood changes were measured.

Luisi and Franchi (1980) in a double-blind, randomised, group comparative study of testosterone undecanoate (120 mg/day orally) and mesterolone (150 mg/day orally) in hypogonadal male patients found that testosterone undecanoate but not mesterolone induced a marked improvement in both sexual activity and mental state (unpublished modified Koch?s Mood Questionnaire) after 2 weeks. These improvements continued for the duration of the 4-week study. No side effects were reported in either group of patients. Using the Lorr and McNair Mood Check List in a double-blind crossover design, Skakkebaek et al. (1981) found significantly improved self-ratings of tension/anxiety and fatigue, a higher level of vigour, but no change in depression with androgen replacement (testosterone undecanoate 160 mg/day orally) versus placebo capsules (oleic acid) in 6 hypergonadotrophic (castration or primary testicular failure) and 6 hypogonadotrophic (hypothalamic or pituitary deficiency) men with hypogonadism. The study was conducted over a 4-month period (2 months on placebo and 2 months on testosterone undecanoate). In addition, there was a significant reduction in self-rated anger during testosterone administration. O?Carroll et al. (1985) also reported significantly improved well-being (4 of 10 self-reported visual analogue scales) with androgen replacement (testosterone undecanoate) in 8 hypogonadal men. A significant does response relationship for well-being was demonstrated with increasing doses (40, 80, 120, 160 mg/day orally) over 4 months.

Wu et al. (1982) using a double blind crossover design and the Lorr and McNair Mood Adjective Check List found no significant change in self-reported mood (anxiety/tension, depression, anger, vigour, fatigue) or energy in 4 adult men (30 to 48 years) with Klinefelters syndrome, low normal testosterone levels and normal sexual activity and interest given testosterone undecanoate (160 mg/day orally) for 8 weeks compared to placebo (8 weeks) and a baseline period of no treatment (8 weeks).

In a double-blind experiment, Davidson et al. (1979) found no consistent relationship between mood (Profile of Mood States) and androgen administration in 6 adult hypogonadal males receiving testosterone enanthate (100 or 400 mg/month in 2 doses) and a placebo treatment in randomly assigned 4-week periods over a 5-month period. Although frequencies of erections showed significant dose-related responses which closely followed the fluctuations in the serum testosterone levels, individual records showed only 1 clear instance of change in mood (POMS) related to treatment (1 subject showed peak increases in anger 1 week after receiving treatment after guessing that he was on placebo). Salmimies et al. (1982) also found no significant differences in biweekly mood ratings when comparing 15 adult hypogonadal male patients administered increasing doses of testosterone enanthate (25, 50, 100, 250mg or placebo) injected over a 5-month period. Each dose was given twice (every 2 weeks) over 4 weeks.

Results from the preceding studies are mixed (table II). Some demonstrate significant positive psychological changes with anabolic-androgenic steroids, others do not. However, no adverse or undesired psychological or behavioural effects were observed in these studies. Interestingly, 5 of the 6 studies which administered oral androgens reported improved mood states following therapy (with the exception of the mesterolone group of Luisi and Franchi); the results of the 2 studies using intramuscular injections of various testosterone esters found no change. However, it should be noted that only perhaps 1 or 2 of the doses administered in these 2 studies (200mg biweekly and 250mg biweekly) would restore and maintain normal physiological testosterone levels and full androgenic function for the entire duration between injections.

O?Carroll and Bancroft (1984), in a carefully controlled double-blind crossover comparison of biweekly injections of 250mg of testosterone esters (?Sustanon?) or placebo in 2 groups of men (n=20) with normal testosterone levels, likewise found no significant change in mood ratings (10 self-reported visual analogue scales) following 12 weeks of treatment (half the subjects in each group received 6 weeks of testosterone followed by 6 weeks placebo, and the other half vice versa).


----------



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 5*

*5. Steroids and Mental Health*
Research and anecdotal information suggested some time ago that steroids have among their many side effects various mental disturbances including schizophrenic symptoms and manic depressive illnesses even though estrone was used successfully in both males and females in the treatment of depression and other mental disturbances occurring with menopause and what would now probably be referred to as andropause beginning in the mid-1930s. Glass (1950) reported that psychoneurotic patients responded more favourably to androgen-estrogen mixtures because these mixtures impart an optimum sense of well-being. 35 years later, Sherwin and Gelfand (1985) reported similar findings of increased energy level and well-being in female surgical menopause patients receiving either a combined estrogen-androgen drug or androgen alone as compared with those receiving estrogen alone or placebo. Although quantification of mood states was generally lacking, it is noteworthy that 23 of 24 studies cited by Kopera (1976) report improvements in psychic as well as physical state, appetite and weight gain in surgical and chronically ill patients treated with anabolic-androgenic steroids. Another 11 of 17 controlled and 11 of 14 uncontrolled clinical trials in geriatric patients cited by Kopera also showed positive anabolic-androgenic steroid effects on physical activity, energy and mood.

It is now well known that, in excess, glucocorticoids can produce extreme emotional instability, ranging from euphoria to suicidal despondency (Hall 1980). Studies of patients with Cushing?s disease indicate that up to 20% could be termed psychotic. Depression is the most common manifestation and suicidal attempts are reported in approximately 10% of cases. Other psychological manifestations include irritability, insomnia, difficulty concentrating, paranoid delusions, hallucinations, and less often, excitement, anxiety, apathy, disorientation, loss of recent memory, and acute organic brain syndrome. Schizophrenic symptoms may also, but rarely, occur. With drug-induced Cushing?s syndrome, in contrast, the most common psychological effect is euphoria, although acute toxic psychosis can also occur.

Mental disorders associated with corticosteroid administration have been documented since the early 1950s (Borman & Schmallenberg 1951; Brody 1952; Byyny 1976; Clark et al. 1952; Glasser 1953). Rome and Braceland (1952) commented that the occurrence of a certain small percentage of psychotic reactions as a compilation of the diseases for which various steroids are administered was to be expected. Train and Winkler (1962) reported a case of homicide involving a woman who had psychotic depression while on corticotrophin and killed her son. Reports continue with still another corticosteroid-related psychotic episode and attempted homicide in 1989 (d?Orban 1989).

Ling et al. (1981) have reviewed the literature to determine the characteristics of corticosteroid-induced mental disturbances and have concluded that: (a) while dosage may be related to the risk of developing mental disturbances, neither dosage nor duration of treatment seems to affect the time of onset, duration, severity, or type of mental disturbances; (b) euphoria as well as depression and psychotic reactions are the most common manifestations of corticosteroid-induced mental disturbances; (c ) females seem to be more prone to these disturbances than males; (d) patients with past mental illness are not necessarily predisposed to such disturbances; and (e) corticosteroid-induced mental disturbances are usually reversible upon dose reduction or discontinuation of the drug. Ling et al. (1981) concluded that there are no simple models to explain the psychotic reactions, anxiety, or agitation seen in corticosteroid-induced mental disturbances. Kaufmann et al. (1982) concluded, in their case report and brief overview, that there are apparently no characteristic symptoms of corticosteroid psychosis. Lewis and Smith (1983) reported in a subsequent review of 14 previously unreported cases of steroid-induced psychiatric syndromes, 79 cases from the medical literature and 29 studies of the clinical efficacy of steroids in various medical illnesses that severe psychiatric reactions occur in approximately 5% of steroid-treated patients, but their review [which contained additional cases not included in Ling et al. (1981)] indicated that a significant proportion of these patients already have existing affective and/or psychotic symptoms. None of their 14 cases had a past history of psychiatric illness unrelated to steroid therapy; 6 (43%) of their 14 cases were thought to have evidence of a premorbid personality disorder; of 41 cases in the literature, 17% had a prior history of psychiatric illness unrelated to steroids; and 52% of the 29 cases were reported to have had an abnormal premorbid personality. Alcena and Alexopoulos (1985) also recently concluded both from their data and a review of the literature on corticosteroid-induced psychiatric disorders that: (a) the pathogenesis of psychiatric symptoms during corticosteroid therapy is unknown; (b) development of psychiatric complications in patients receiving corticosteroids is probably dose-dependent; (c ) the type of psychiatric manifestations is variable; (d) it is unclear whether a history of psychiatric disorders increases the risk for psychiatric problems from corticosteroids; and (e) in the majority of patients, psychiatric complications remit when the dosage of corticosteroids is reduced or administration discontinued.

With respect to withdrawal symptoms, it is worth noting that symptoms of Addison?s disease include apathy, depression, fatigue, a general lack of interest, initiative and motivation, and an overall negativism (Hall 1980). In acute Addison?s disease a typical organic psychosis develops with memory deficit and clouding of consciousness. Administration of aldosterone improves electrolyte balance, but corticosteroid administration is necessary to correct the personality disturbance, EEG abnormalities and altered sensory thresholds.

Considering then the structural similarities of cortical and anabolic steroids and their multiple additive and synergistic as well as competitive actions, it is not surprising that their administration would result in some similar effects on mood and behaviour. Furthermore, anabolic-androgenic steroid administration has been reported to alter glucocorticoid metabolism (James et al. 1962), and high doses of anabolic-androgenic steroids given to athletes have been shown to dramatically elevate serum and urinary cortisol levels (Hervey et al. 1976), although other studies have not corroborated this latter finding (Alen et al. 1985).

Androgens, on the other hand, have been used in the treatment of mental disorders for over 50 years. Werner et al. (1934) used theelin (estrone) to treat female patients suffering from involutional melancholia (depression) and reported improvement in 18 of the 20 cases attended. 90% (versus 16% in a control treatment) of the 39 female patients (34 to 58 years) with involutional melancholia treated with daily intramuscular injections of theelin over 6 months showed slight to marked improvement in a study by Werner et al. (1936). Using larger doses, Ault et al. (1937) later treated 14 female cases of involutional melancholia with a recovery rate of 92%. However, although no adverse reactions were reported, the results for treatment of mental disorders with theelin was not always successful (Schube et al. 1937).

In a review of the literature, Danziger (1942) reported that while estrone therapy was not highly successful for the treatment of female involutional melancholia, the incidence of recovery or marked improvement was better than no treatment and, in his own investigation, found 4 of 7 female patients benefited from the daily oral administration over several month of diethylstilbestrol.

Schmitz (1937) produced improvement with testosterone propionate in 86% of 42 cases with symptoms such as depression and impotence in males in the involutional age. Foss (1937) relieved depression in a eunuch by the daily injection of 20mg of testosterone propionate.

Hamilton (1937) reported that a 27-year-old male hypogonadal subject treated with testosterone acetate (a total of 550mg over a period of 1 month) became more energetic, virile and self-assured during therapy. Testosterone propionate 10mg 3 times weekly relieved the subjective symptoms (anxiety, depression, fatigue) in 2 male climacteric patients (Werner 1939). Two cases diagnosed as male climacteric (involutional melancholia) and treated with moderate amounts of testosterone propionate (10 to 30 mg/week) for short periods of time (6 to 8 weeks) by Thomas and Hill (1940) made ?remarkable improvement? both during and subsequent to treatment. Likewise, Guirdham (1940) reported mental improvement in 4 males suffering from a variety of psychological disorders after being treated with intramuscular injections of testosterone propionate and androsterone benzoate (5 mg/day).

Lamar (1940) also reported improvement in 4 male climacteric patients treated with varying doses of testosterone propionate over several months. Palmer et al. (1941) reported improved mental states in 5 of 10 male involutional melancholia patients treated with testosterone propionate over several months. 65% of the 20 male patients (versus 46% in the control group receiving routine hospital procedures) suffering from involutional psychoses treated with intramuscular injections of testosterone propionate (30 to 75 mg/week) for a period of 6 to 12 weeks responded well in a study by Davidoff and Goodstone (1942).

Using ?massive dose? (1300mg over 40 days) testosterone propionate therapy to treat 5 cases of male involutional psychosis, Zeifert (1942) reported 2 patients improved sufficiently to warrant release, 2 others improved during treatment but relapsed shortly thereafter, and 1 failed to show any change. No harmful effects were observed during the experiment despite the administration of relatively high doses of testosterone propionate.

Werner (1943) reported that 24 of 26 middle-age male climacteric patients receiving intramuscular injections of testosterone propionate 30 to 75 mg/week benefited by relief of symptoms and a sense of well-being. Heller and Myers (1944) recommended regular intramuscular injections of testosterone propionate 25 mg to obtain satisfactory therapeutic results in the male climacteric.

Danziger and Blank (1942) reported an overall success rate of nearly 70% for androgen treatment of depressed males in a review of the literature and, in their own investigation, found that 3 of 5 patients benefited from the weekly intramuscular administration of 75 to 150 mg of testosterone propionate. Two years later, Danziger et al. (1944), in another literature review, reported that the incidence of prompt recovery for testosterone-treated male patients with involutional melancholia was significantly higher than the incidence of prompt spontaneous recovery for control patients. In the same investigation, using 9 additional male patients with involutional melancholia, the authors found recovery and improvement in 6 patients following injections of testosterone propionate (25mg) 3 times per week over several month.

Altschule and Tillotson (1948) found that intramuscular administration of testosterone in large doses (350 mg/week) over 2 to 3 weeks was followed by remission of mental symptoms in 18 of the 31 (28 male) psychiatric patients that they treated.

Again, as with estrone, results with testosterone propionate were not always so positive. In 1939, the Council of Pharmacy and Chemistry of the American Medical Association refused to accept testosterone for New and Nonofficial Remedies stating, ?the involutional melancholia of males, for which testosterone has been suggested, has not been subjected to adequate trials, to justify androgenic therapy other than on an experimental basis.? No ?noticeable improvement? in mental condition was found in 5 cases of male involutional melancholia who were treated with intramuscular injections of testosterone propionate 10mg 3 times weekly for a period of 3 to 4 weeks by Barahal (1938). Barahal (1940) also found little or no change in the mental condition of 7 psychotic male homosexual patients who were treated with intramuscular injection of testosterone propionate (25mg) 3 times weekly for 18 months. In addition, Pardoll and Belinson (1941) reported that mental improvement was not sufficiently pronounced to warrant administering testosterone propionate as routine treatment for the male involutional psychoses after treating 11 males with 10mg doses of testosterone propionate twice weekly for 3 months and observing behaviour for 2 months following cessation of therapy.

11 of 12 male involutional melancholia patients (53 to 64 years), treated with intramuscular injections of testosterone propionate (1500mg) over 8 months, showed no improvement either during or after treatment, leading Kerman (1943) to conclude that testosterone propionate had little or no effect in the treatment of male involutional melancholia. Simonson et al. (1944) found significantly increased (compared to a placebo period) fusion frequency of flicker and back-muscle strength in 6 older male subjects (46 to 67 years), who had complained of fatigability, following oral treatment with methyl testosterone (30 to 40 mg/day) over 6 to 45 weeks. The results appear to be compatible with the hypothesis that maintenance of a higher level of male sex hormone has an influence on the depression of working capacity with age.

Strauss et al. (1952) reported improved mental states in 6 of 8 male patients with schizophrenic illness treated with various doses of dehydroisoandrosterone over several weeks. However, increased aggressiveness and nervous tension occurred in the other 2 patients during the course of treatment. Sands and Chamberlain (1952) reported significant improvement in 13 juveniles with inadequate personality following the administration of dehydroisoandrosterone (10 to 20 mg/day) for 2 to 11 weeks. Again, however, those patients who tended ?to be overaggressive in mental make-up were made worse and appeared overstimulated by the drug.?

Burnett (1963) used a placebo-controlled study with 38 chronically ill male and female geriatric mental patients (36 of whom were past the age of 60) to determine the effect of anabolic-androgenic steroids (6 mg/day of stanozolol for 5 month) and found that ?mental outlook? improved in 5 of the 18 anabolic-androgenic steroid-treated patients compared with 1 of the 20 placebo-treated patients. MacMaster and Alamin (1963) treated 47 underweight, mentally disturbed female patients ranging in age from 15 to 86 years with methandrostenolone 5 to 15 mg/day over 29 to 60 days and reported an improvement in appetite, a feeling of well-being and an improved psychological attitude. Tec (1974) has described limited success in improving ?general psychic condition? following administration of the decanoate ester of nandrolone (2 intramuscular injections of 25mg over 2 weeks) in a young female suffering from anorexia nervosa. A sense of increased well-being was also reported by Sansoy et al. (1971) in a study of 34 male and female mental patients (ages 22 to 104 years) who received 15 to 20mg of oxandrolone daily for 8 weeks. Wynn and Landon (1961) reported that a wide range of dose (25 to 100 mg/day) and length of administration (6 to 260 days) of methandienone produced a sense of well-being and increased confidence without restlessness, nervousness, or insomnia in 19 of 30 male and female patients with various disorders. In a double-blind study by Jakobovits (1970) of 100 impotent elderly male patients, a favourable response was seen in 78% of the patients treated with methyltestosterone thyroid for 1 month, whereas a favourable response was seen in only 40% of the cases treated with placebo. No adverse effects or chemotoxicity was noted in any of the patients.

Itil (1976) treated 5 male psychiatric (depressed) patients with daily doses of 2 to 6mg of the nonaromatisable oral androgen mesterolone for 24 days and within a week subjects showed a decrease in depressive mood, sadness, and particularly feelings of inadequacy based on clinical observations. Increasing the dosage from 25 to 200 mg/day resulted in 4 of 5 other male psychiatric (depressed) patients demonstrating improved mental states. Other studies by Itil et al. (1974, 1979) have confirmed that this compound results in electroencephalographic effects that are, as previously indicated, depending upon the dose, similar to stimulants (such as amphetamines) and tricyclic antidepressants. Beumont et al. (1972) found administering methyltestosterone (25 mg/day) over 8 weeks to a male patient resulted in the specific and rapid loss of both depressive and phobic symptoms. Pope and Katz (1988) report the prompt remission of weekly panic attacks in a 40-year-old female subject with a history of panic disorder following self-administration of oxandrolone (20 mg/day). Vogel et al. (1985) compared the antidepressant effects of amitriptyline (75 mg/day, up to a maximum of 300 mg/day) and mesterolone (100 mg/day, up to a maximum of 550 mg/day orally) in a double-blind parallel treatment design with 34 depressed male outpatients and found that the 2 drugs were equally effective in reducing depressive symptoms and that mesterolone produced significantly fewer adverse effects than amitriptyline.

Wilson et al. (1974), in contrast, found that 4 of 5 depressed men treated with methyltestosterone (15 mg/day orally) and the tricyclic antidepressant imipramine (25 to 50 mg/day) orally simultaneously, promptly showed a paranoid response that cleared rapidly when treatment with the hormone was discontinued. They hypothesized that the shift from depression to a paranoid reaction may have resulted from an increase in aggression, which in turn may have been the result of the interplay between the hormone and the drug and the effects of this interplay on brain monamine metabolism. The findings of Wilson et al. (1974) are not unexpected given the fact that testosterone is known to inhibit MAO activity. Concomitant administration of a substance (such as imipramine) which would additionally elevate monoamine levels by inhibiting reuptake could well be expected to induce moodiness, paranoia, and depression, a biphasic response that has been shown to occur with administration of increasing doses of estrogen, another inhibitor of MAO.

Even after reviewing the report of Wilson et al. (1974), Hollister et al. (1975) suggested that ?small doses of androgens might be useful as adjuncts to potentiate the effects of small doses of tricyclics in patients who cannot tolerate the anticholinergic side effects of large doses.? Clinical studies and hormonal therapy for mental illness have, however, presumably been preempted by the development and marketing of a wide variety of newer pharmacological agents.

Tilzey et al. (1981) have also reported a case involving a 66-year-old male patient with symptoms of severe anaemia who developed toxic confusional state and choreiform movements after several months of treatment with an anabolic-androgenic steroid (oxymetholone 200 to 300 mg/day orally) and improvement upon withdrawal of the drug. This represents a relatively large dose since the normal daily dose is between 50 and 200 mg/day. The onset of symptoms and remission following cessation of administration suggested that the drug played a significant role in the aetiology of the observed symptoms.

The findings of the preceding studies nevertheless generally indicate positive rather than negative effects following androgen therapy in mental (especially depressed) patients. However, it is unknown whether long term use or use of pharmacological doses by otherwise healthy individuals, particularly adolescents, might result in similar outcomes. A summary of these studies is provided in table III.


----------



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 6*

*6. Anabolic Steroids, Athletes and Behaviour*
Very few scientific studies are available of either the personality and psychological characteristics or the changes that might be incurred as a result of heavy resistance training in competitive weightlifters and bodybuilders (Harlow 1951; Henry 1941; Thune 1949). Further, there is little understanding of the extent to which resistance (or other) training may develop and/or facilitate the expression of aggression. In a study of 10 competitive female bodybuilders, Freedson et al. (1983) found this group of athletes to be somewhat less anxious, neurotic, depressed, angry, fatigued, and confused and more extraverted, vigorous and self-motivated [State-Trait Anxiety Inventory, Profile of Mood States, Self-Motivation Inventory (Dishman et al. 1980), and Eysenck Personality Questionnaire] than the general population indicating ?good mental health?. Unfortunately, no mention is made by Freedson et al. (1983) as to whether their subjects were anabolic-androgenic steroid users.

Psychological and behavioural changes, such as increased aggressiveness and irritability, have been reported on an anecdotal basis by athlete anabolic-androgenic steroid users as well as their families and friends (Goldman et al. 1984; Taylor 1982, 1987a,b; Wright 1978, 1982). It is possible, however, that, as occurs with so many drugs, many of the subjectively-perceived psychological and behavioural changes reported by anabolic-androgenic steroid users are a direct result of expectancy, imitation or role modeling. Observing the actions of other anabolic-androgenic steroid users and athletes may greatly influence the expectations and behaviours of those in the initial and early continuation phases of use. In addition, aggressive or even violent behaviour that may be unacceptable outside the athletic environment may not only be fully acceptable but actually encouraged and even required within the within the weight room or on the playing field.

Brooks (1980), Wilson and Griffin (1980), and Ryan (1981) have suggested that some if not most of the ergogenic benefits of anabolic-androgenic steroids may derive from their psychological effects. It is possible that anabolic-androgenic steroid use may elevate arousal (Rejeski et al. (1988b), increase self-confidence and pain threshold (Holzbauer 1976), and facilitate expression of the ?all-out? physical effort demanded during training and competition in a variety of sports. In the absence of adequate external forces, internal discipline, or social coping skills, these phenomena could lead to expression of aggression at inappropriate times. In this regard it is interesting to note that many times the behaviour associated with criminal actions is frequently ?not intended to hurt anyone?.

Rozenek (1985) examined the effects of an acute bout of resistance exercise and self-administered anabolic-androgenic steroids on various physiological parameters and mood states. In addition, resistance training (62.5% of 1 repetition maximum strength capacity in various exercises) was compared to endurance activity of similar intensity (62.5% of VO2max) and duration (47 minutes). 23 subjects were divided into 4 groups: 8 nonuser weightlifters; 5 weightlifters self-administering anabolic-androgenic steroids; 5 runners; and 5 sedentary controls. The POMS questionnaire was administered prior to, immediately following, and 30 minutes after a bout of exercise. Significant differences in mood were observed among groups. Both groups of weightlifters, including those self-administering anabolic-androgenic steroids, had higher scores in confusion-bewilderment, fatigue-inertia, and total mood disturbance than both groups of runners and controls. In addition, the anabolic-androgenic steroid-using weightlifter group had a significantly higher anger-hostility score immediately following exercise than any of the other 3 groups. Rozenek (1985) concluded that dynamic resistance exercise resulted in different psychological responses from endurance exercise of similar relative intensity and duration and that anabolic-androgenic steroids may alter the response normally seen during exercise and recovery.

Hevery et al. (1976) reported that one benefit of taking anabolic-androgenic steroids, as expressed by some athletes, lay in the reduction of fatigue during the training season, which allows for more training to be done. Freed et al. (1975) provide anecdotal and self-report information that athletes using anabolic-androgenic steroids are generally less easily fatigued, allowing for longer, more frequent and/or intense training sessions. This could be related to the fact that anabolic-androgenic steroids can block and reverse the anticatabolic effects of glucocorticosteroids that are released during periods of stress including physical exertion (Kochakian 1976; Kruskemper 1968; Williams 1981). Work with rats has also demonstrated reduced alkaline protease activity (Dahlmann et al. 1981) and increased glycogen supercompensation (Gillepsie & Edgerton 1970) in androgen-related animals. Brooks (1980) has suggested that the increases in aggression and energy that the athletes feels may be the result of neurological changes previously discussed. In cases where anabolic-androgenic steroids do improve physical or physiological capacities or performance, the improvement is likely due to some extent to increases in training per se as well as to any pharmacological effect. Despite these suggestions and self-reports, scientific data supporting the notion that psychological changes (enhanced arousal, confidence, aggression, motivation) play a primary role in mediating any ergogenic effects of anabolic-androgenic steroids is lacking.

Strauss et al. (1983) in a study of the side effects of anabolic-androgenic steroids (375 +/_ 57 mg/week) in 32 weight-trained men found that 56% reported a temporary increase in self-defined irritability and aggressive behaviour during anabolic-androgenic steroid use which consisted of increased arguments or irritability when dealing with others. Some respondents also reported an increased tendency to engage in physical fighting. Strauss et al. (1985) also found that 8 of 10 female athletes using anabolic-androgenic steroids in a later study reported increased, albeit self-defined aggressiveness, which pleased 6 of these athletes, because it enhanced their drive to train and compete. However, some reported that their aggressiveness caused problems in relating to associates and family members.

Haupt and Rovere (1984) have reviewed 13 studies reporting subjective side effects during the administration of anabolic-androgenic steroids and found over 30% of the subjects questioned reported transitory side effects such as changes in libido (increased and decreased) and increased aggressiveness.

Annitto and Layman (1980) have described a single case which relates the use of an anabolic-androgenic steroid (purportedly methandienone, dose not provided) obtained on the black market to the development of an acute schizophrenia illness in a 17-year-old male who took up bodybuilding to compensate for being picked on by other children due to his frail nature. Symptomatology began approximately 6 months after initiating anabolic-androgenic steroid use and subsided with discontinuance. However, as Annitto and Layman state, they were unable to ??definitely demonstrate that the use of this medication was etiopathogenic in this young man?s illness?? Freinhar and Alvarez (1985) have reported on a case of anabolic-androgenic steroid-induced hypomania in a probably cyclothymic personality. The patient, a 27-year-old male bodybuilder with no previous major psychiatric dysfunctions or psychoses, but a tendency toward periodic depressions without vegetative symptoms alternating with hyperactivity and increased libido, began self-administering a synthetic androgen (oxandrolone, source unknown, at a reported dose of 6mg orally twice daily). (Since oxandrolone is typically available only in 2.5mg tablets, the reported dose itself raises questions about the accuracy of the drug or dose taken.) Nevertheless, within 6 days the patient began to feel irritable, somewhat hyperactive, noted a decrease in sleep, and an overall increase in energy level. Within a week, he began to ?feel good all the time?, described ?thoughts running around in my head?, experienced hyperphagia and hypersexuality. A tentative diagnosis of steroid-induced hypomania was formulated. When androgen consumption was terminated, all symptoms disappeared within 3 to 4 days. However, a week later the patient resumed self-administration of anabolic-androgenic steroids (oxymetholone, dose and source unknown/unreported) and again presented with similar symptoms. Despite being informed of the possible long term consequences of using this drug, the patient decided to continue his self-prescribed regimen and did not return for further treatment.

Pope and Katz (1987) studied 2 men who required hospital admission for psychotic episodes apparently associated with the use of anabolic-androgenic steroids (methyltestosterone 20 mg/day orally in a 40-year-old treated with anabolic-androgenic steroids for idiopathic impotence and methandrostenolone 15 mg/day orally in a 22-year-old bodybuilder). Neither individual reported any previous serious psychopathology and both, with no further exposure to anabolic-androgenic steroids, remained psychiatrically normal during more than 2 years of follow-up. Consequently, Pope and Katz concluded that anabolic-androgenic steroids were likely a causative factor in both cases.

Pope and Katz (1988) also interviewed 41 (39 male) additional anabolic-androgenic steroid users using a structured diagnostic interview. Self-reports of various psychiatric syndromes during anabolic-androgenic steroid use were compared with periods of no anabolic-androgenic steroid use. Results indicate that according to DSM-IIIR criteria (Spitzer et al. 1986), 5 subjects (12%) manifested psychotic symptoms, 4 others (10%) had ?subthreshold? or equivocal psychotic symptoms, 5 subjects (12%) reported a manic episode, and 9 (22%) developed a full affective syndrome during anabolic-androgenic steroid use. It is unclear whether these groups were mutually exclusive. None of the 41 subjects recalled adverse effects of anabolic-androgenic steroids sufficient to require medical consultation and apparently none sought treatment for their mental health disturbances. Although Pope and Katz do not elaborate on their recruitment of participants, other than to report that they were volunteers obtained by advertisements at 38 gymnasia in the Boston (26 gyms, 22 subjects) and Santa Monica (12 gyms, 19 subjects) areas and paid US$25 for a confidential interview, they do indicate that ??despite our considerable efforts at recruitment, only a minority of steroid users were willing to be interviewed.? Unfortunately, their difficulty in obtaining subjects raises questions about the representativeness of their sample relative to the population of anabolic-androgenic steroid users. Given the vast pool of potential participants, their difficulty in obtaining volunteers could suggest a low incidence of psychiatric problems among anabolic-androgenic steroid users as well as a basic mistrust of the medical and scientific establishment. It is conceivable that those anabolic-androgenic steroid users who elected to participate in the study were individuals with the greatest severity and frequency of mental disturbance. It is also probably safe to assume that individuals willing to take anabolic-androgenic steroids and other drugs of questionable origin, content and purity, and with serious legal as well as health effects, differ from the population on a wide variety of characteristics including mental health. 15% of Pope and Katz?s subjects reported past alcohol abuse or dependence and 32% reported other prior substance abuse or dependence including cannabis (17%) and cocaine (12%). Interpretation of the reports of these subjects must be tempered by the absence of information regarding the extent to which their use occurred concurrently with anabolic-androgenic steroids and with psychiatric symptoms and by the absence of knowledge on the interaction of anabolic-androgenic steroids and such drugs of abuse. 17% had a first degree relative with a major affective disorder and 2 subjects reported symptoms of a full affective disorder when not taking steroids. Finally, while it is difficult to establish the extent to which anabolic-androgenic steroids may have contributed to the psychotic episodes reported by Pope and Katz, and while the media may have sensationalised their findings somewhat (Editorial 1988a,c), it seems likely that, with more widespread use of anabolic-androgenic steroids and increased efforts to document such reactions, additional cases will be forthcoming.

As part of an effort to assess physiological and psychological states accompanying anabolic-androgenic steroids usage, Wright et al. (1986) examined the psychological characteristics and subjectively-perceived behavioural and somatic changes accompanying steroid usage in 12 current anabolic-androgenic steroid users. The results obtained from these users were compared with results obtained from 14 previous users (no use more recent than 1 month) and 24 nonusers. Although both current and former users reported subjectively perceived changes in enthusiasm, aggression, irritability, insomnia, muscle size, and libido when using anabolic-androgenic steroids, these changes were not confirmed in comparison across groups using standardised psychological inventories (POMS and BDHI). The presence of subjectively perceived, anabolic-androgenic steroid-associated behavioural and somatic changes in the absence of significant differences in standard psychological inventory responses illustrates the complexity of these relationships and dictates a need for additional research. The findings of Wright et al. (1986) are both compatible with and complimentary to anecdotes, case reports and data from individual psychiatrists. The ?negative? findings do not negate the possibility of anabolic-androgenic steroids precipitating aberrant behaviour in some users. Our general impression, however, is that irritability is slightly increased in many users and that in a small number of users who are premorbid, anabolic-androgenic steroid use may well be sufficient to ?push them over the edge? and contribute to irrational or violent behaviour, particularly where the use of other drugs of abuse are involved (Bahrke et al. 1990). The results of the preceding studies are summarised in table IV.


----------



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 7*

*7. Psychological Dependence and Withdrawal Effects of Anabolic Steroids*
For the most part, individuals use anabolic-androgenic steroids to significantly improve appearance and/or performance beyond what would be expected from training alone. Also, individuals using anabolic-androgenic steroids appear to believe that higher doses and continued use result in greater gains, a belief that receives support from animal biochemistry studies (Bardin et al. 1990), from clinical responses in some anaemias (Sanchez-Medal et al. 1969), as well as from studies in athletes (Alen &Hakkinen 1985; Alen et al. 1984, 1985, 1987; Forbes 1985; Hakkinen & Alen 1986; Hervey et al. 1976, 1981; Kilshaw et al. 1975). When individuals discontinue using anabolic-androgenic steroids their size and strength diminish, often very dramatically (Alen & Hakkinen 1985; Alen et al. 1984, 1987; Forbes 1985; Hakkinen & Alen 1986), and this outcome, as well as any psychological effects of use which serve to create a new body image, improved self-esteem, heightened libido and general euphoria, are thought to motivate continued use of anabolic-androgenic steroids (Yesalis et al. 1989a, 1990b).

Yesalis et al. (1989a) found that approximately a quarter of adolescent anabolic-androgenic steroid users reported behaviours, perceptions, and opinions which as consistent with psychological dependence. These high school users were significantly different from nonusers in several areas including self-perceptions of health and strength. The majority perceived their relative strength to be greater than average and their health as very good or better. Also, heavy users (+/= 5 cycles) were more likely, relative to other users, to use injectable anabolic-androgenic steroids, express intentions to continue to use anabolic-androgenic steroids regardless of health consequences, and take more than one anabolic-androgenic steroid at a time.

As with corticosteroids (Alcena & Alexopoulos 1985; Alpert & Seigerman 1986; Amatruda et al. 1965; Byny 1976; Dixon & Christy 1980; Judd et al. 1983; Kaufmann et al. 1982), increasing attention and discussion is being focused on the withdrawal effects that athletes encounter when they cease use of anabolic-androgenic steroids. Interestingly, many of the same effects attributed to anabolic-androgenic steroid use are alleged to occur following anabolic-androgenic steroid cessation. Purported withdrawal effects include mood swings, violent behaviour, rage and depression, possibly severe enough to lead to thoughts of suicide (Brower et al. 1989a,b 1990; Goldman et al. 1984; Editorial 1989). Pope and Katz (1988) report that 5 of their subjects (12%) developed major depression while withdrawing from anabolic-androgenic steroids. Duncan and Shaw (1985) suggest that weight and fluid loss may worsen (or be the cause of) the impending depression.

Tennant et al. (1988) recently described the case of apparent physical dependence on anabolic-androgenic steroids in a 23-year-old male bodybuilder who had been using anabolic-androgenic steroids (methandrostenolone 75mg and methenolone 150mg intramuscularly every other day and oxandrolone 20mg and oxymetholone 100mg orally each day) for 3 years and who was unable to abstain from anabolic-androgenic steroids without experiencing severe withdrawal symptoms, including depression, disabling fatigue and violent, paranoid, and suicidal thoughts and feelings. Urinalysis was negative for alcohol, amphetamines, cannabinoid metabolites, cocaine metabolites, opioids and phencylcidine. Classic opioid withdrawal symptoms appeared following naloxone administration and anabolic-androgenic steroid cessation. However, despite being treated with clonidine over the next 6 days and a decrease in withdrawal symptoms, the patient left the treatment programme and apparently resumed use of anabolic-androgenic steroids 7 days after admission.

Brower et al. (1989a) reported the case of a 24-year-old male noncompetitive weightlifter whose dependence on a combination of anabolic-androgenic steroids (200mg of testosterone cypionate intramuscularly every 3 days, 100mg of nandrolone decanoate intramuscularly every 3 days, 25mg of oxandrolone orally daily, 30 to 45mg of bolasterone subcutaneously every 2 to 3 days, and 1000 to 2000 units of human chorionic gonadotrophin intramuscularly every 2 to 3 days) met criteria for psychoactive substance dependence. Tolerance, withdrawal symptoms (depression, fatigue), and the use of anabolic-androgenic steroids to alleviate withdrawal symptoms had occurred. An uncontrolled pattern of anabolic-androgenic steroid use continued, despite adverse consequences such as severe mood disturbance (irritability, euphoria, anxiety, depression), marital conflict, and changes of the patient?s usual values and life goals.

Hays et al. (1990) also have reported a similar case in which a 22-year-old male noncompetitive weightlifter who had been using anabolic-androgenic steroids for 9 months (25mg of oxandrolone daily, nandrolone phenpropionate, testosterone propionate intramuscularly each week, and methandrostenolone) presented with complaints of depression and inability to cease anabolic-androgenic steroid use. The patient felt depressed, fatigued, had occasional temper outbursts, and slept less when taking the steroids. Steroid craving and decreased self-esteem were reported between periods of steroid use. Following 1 week and improvement in mood, the man was discharged from the hospital chemical dependency treatment unit.

In another study by Brower et al. (1990) of 8 anabolic-androgenic steroid-using weightlifters, all reported both withdrawal symptoms and uncontrolled use despite adverse consequences (feeling nervous, irritable, or depressed). Psychiatric, especially depressive, symptoms were prominent in most of the dependent users. Brower (1990) has suggested that some conventional drug abuse treatments such as pharmacotherapy (used with cocaine withdrawal) or psychotherapy may be effective with dependent anabolic-androgenic steroid users.

Finally, Kashkin and Kleber (1989) in their review, suggest that the psychoactive effects, withdrawal symptoms, and underlying biological mechanisms of steroid hormones, including anabolic-androgenic steroids, appear similar to the mechanisms and complications accompanying cocaine, alcohol or opioid abuse. They concur that a proportion of anabolic-androgenic steroid abusers may develop a sex steroid hormone dependence disorder and that treatment should be based on research into steroid effects on both opioid and aminergic neurotransmission systems and relapse prevention. It is both interesting in this regard, and suggestive of the difficulties facing drug abuse researchers and educators, that a study by Johnson et al. (1970) of the effects of testosterone enanthate (200mg intramuscularly once every 4 weeks over 7 months) on body image and behaviour in 5 young mentally retarded males with Klinefelter?s syndrome included not only a significant change from a feminine to a masculine body image, increased assertiveness, increased goal-directed behaviour and heightened sexual drive, but the majority of subjects expressed ??a desire to become further masculinised.?

These preceding findings must be tempered by the fact that individual responses to different anabolic-androgenic steroids, doses, and lengths of administration likely vary somewhat unpredictably. Further, beyond these reports, no threshold dosage that may produce these effects (mood swings, violent behaviour, rage, depression) or timecourse concerning the onset or elimination of these effects once anabolic-androgenic steroid use has been initiated or terminated have been fully documented (which may depend, in part, on the length of anabolic-androgenic steroid use, particular desired as well as undesired effects experienced, and a host of other factors). As Svare (1990) has indicated, several critical variables involved in modulating the behavioural effects of androgens in animals including sex, dose/duration, route of administration, type of androgen, and genotype, must be addressed when examining human anabolic-androgenic steroid abuse. Finally, weighttraining per se may be addictive in the sense of promoting compulsive, stereotypic, and repetitive behaviour to include not only the strength training but dieting, drug use and a host of other lifestyle variables as well.


----------



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 8*

*8. Prevention and Treatment of Anabolic-Androgenic Steroid Abuse*
The use of educational intervention programmes for the prevention and treatment of anabolic-androgenic steroid abuse has been examined in several studies. Hallagan et al. (1990) propose that education is the most feasible alternative for curbing steroid use by adolescents. On the otherhand, Bents et al. (1990) found that an educational programme which emphasised alternatives to anabolic-androgenic steroid use, such as nutrition principles and strength training techniques was more effective in improving attitudes towards potential steroid use than either an educational programme in which no alternatives were discussed or no intervention programme. Likewise, Frankle and Leffers (1990) suggest that education alone may not be as effective as clinical assessment and consultation in the care of individuals abusing steroids. Rosse and Deutsch (1990) report that benzodiazepine agents might prove useful in the amelioration of the symptoms of steroid withdrawal.


----------



## Arnold (Jan 16, 2020)

*Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males: A Review, Part 9*

*9. Discussion of Major Methodological Issues in Anabolic Steroid Research*
As noted previously, any attempt to evaluate and summarise the psychological and behavioural effects associated with the use of anabolic-androgenic steroids is complicated by the numerous methodological shortcomings of many of the investigations, including inappropriate sampling strategies, lack of adequate control groups, use of several types, doses and length of administration of anabolic-androgenic steroids, and a variety of techniques used to assess the psychological and behavioural outcomes.

*9.1 Sample Selection and Size*
A significant number of studies did not control for or report family or previous personal history of mental illness and /or aggressive behaviour, thereby resulting in a possible selection bias in the study population. In addition, selection of physically and/or mentally ill patients, persons, volunteers, etc. as subjects, raises the question of the generalisability of the findings to otherwise healthy individuals. Many of the studies reviewed here have been conducted with small sample sizes, thus reducing the statistical power available to detect significant differences. Furthermore, small sample sizes have precluded examination of steroid effects in additional subgroups such as age, race, gender, educational level and social class. Small sample size makes it difficult to control for potential confounding variables using multivariate statistical techniques. Sampling of blood and urine was inconsistent among studies, and often unreported, with respect to timing and multiple samples were often not obtained.

*9.2 Control Subjects*
A number of studies failed to incorporate control groups. Subjects who act as their own controls in a repeated measures design would be a possible exception. Many studies, for ethical and legal reasons, did not randomly assign subjects to treatment, use comparable reference groups, or take advantage of single- or double-blind designs.

*9.3 Steroids Investigated*
Not all anabolic-androgenic steroids are the same; significant variation among anabolic-androgenic steroids regarding acute physical effects has been noted (Herrmann & Beach 1976; Kruskemper 1968; Williams 1981), and Bardin et al. (1990) have reported that there is significant individual variation in response to the same androgen and dose.

Kochakian (1990) has also pointed out the possibility that adverse reactions may represent toxic responses in some individuals. Caution must be exercised when attempts are made to generalise the psychological and behavioural effects (findings) from a study using one type of anabolic-androgenic steroid to a different steroid used in another study. Also, while reporting the average steroid dose used, some studies failed to examine or report any dose-response relationship. In addition, even when dosage was provided, estimating the bioavailability equivalence between oral and injectable anabolic-androgenic steroids is difficult. Moreover, in hypogonadal patients it appears that oral anabolic-androgenic steroids are the only type of anabolic-androgenic steroids that produce positive mood changes, although the doses of injectable steroids administered in these studies often tended to be below those required to restore and maintain normal plasma testosterone levels. In other users (athletes) it is the oral anabolic-androgenic steroids that are associated with the adverse psychological changes.

Svare (1990) has also stated that another important variable determining the effectiveness of anabolic-androgenic steroids in promoting aggressive behaviour is whether the anabolic-androgenic steroids are aromatisable. Furthermore, the measurement of the concentration of anabolic-androgenic steroids or other drugs in biological samples has not been performed in subjects whose behaviour has been observed or changed according to self-report. Finally, since as much as 50 to 80% or more of the anabolic-androgenic steroids used by athletes may have been obtained from black market sources (Frankle et al. 1984; Yesalis et al. 1988; unpublished data, our laboratories), case reports of individuals using these drugs must be evaluated accordingly given the absence of knowledge concerning their actual content.

*9.4 Assessing Aggression and Aggressive Behaviour*
Defining aggression and assessing aggressive behaviour is itself difficult. As stated by Kreuz and Rose (1972), ?Behaviors encompassed by the common usage of the term ?aggressive? range from normal assertive and coping behaviours to acts of violence.? The term ?aggression? includes a diverse category of phenomena including behavioural, emotional, and motivational aspects. Aggression may be expressed in many ways. It may be overt (e.g. cursing) or covert (e.g. gossiping), direct (e.g. physical assault) or indirect (e.g. verbal hostility). Various definitions and theories of aggression have been proposed (Bandura 1973; Berkowitz 1962; Lorenz 1966). While one definition suggests that aggression is ?any sequence of behavior, the goal of which is to do injury to the person toward whom it is delivered? (Dollard et al. 1939), the intentions of the aggressor, whether to commit injury or to achieve a reward, are critical factors (Dollard et al. 1939). Social learning theory proposes a comprehensive model that includes as causative factors the immediate and long term social setting as well as the emotional and cognitive combination of aggressor and victim (Bandura 1973). The significance of imitation, modelling, and future rewards attached to expressing aggressive behaviours, especially in sports, must also be considered (Bandura 1973).

*9.5 Psychological Inventories*
Since a variety of psychological inventories were used (Buss-Durkee Hostility Inventory, Minnesota Multiphasic Personality Inventory, Profile of Mood States, etc.) across studies, comparability of findings between studies is difficult. In some cases, nonstandardised and/or unpublished inventories were used. As a result, some of the questionnaires may have been inadequate for detecting behavioural change. In addition, if inventories such as the BDHI assess the trait of hostility and not the state of hostility, it is possible that testosterone level is not correlated with the enduring personality characteristics of hostility but rather with the temporary state of hostility. Although long term high dose use may elicit lifestyle changes, it is worth noting that witnesses involved in criminal proceedings against anabolic-androgenic steroid users often comment that ?He became a different person?after beginning anabolic-androgenic steroid use? (Conacher & Workman 1989; Editorial 1989; Katz & Pope 1990; Lubell 1989; Moss 1988). In general, however, as Rose (1974) has pointed out, it is more likely that testosterone (or anabolic-androgenic steroid concentration in general) is correlated more with assertiveness or an action orientation than with assaultive, combative, or violent physical or verbal aggression.

*9.6 Self-Reported vs Observed Alterations in Behaviour*
An overriding concern is the accurate documentation of any change in behaviour with anabolic-androgenic steroid use. No studies of actual behaviour (e.g. aggressive behaviour) while in athletic competition have been reported. Some studies were unclear regarding how changes in behaviour associated with anabolic-androgenic steroid use were determined. It is possible that some of the behavioural differences reported resulted from some investigations relying upon self-reports and other self-defined (user and researcher) measures of behavioural change (inventories and diaries), while others used observers and/or interviews to document behavioural changes. Consequently, aggressive feelings that failed to manifest as aggressive actions may have either gone unrecognised or been overreported. Zuckerman et al. (1967) have reported that the sum of the hostility responses from the BDHI is significantly related to clinical ratings of hostility based on both observed and inferred estimates. However, despite this evidence that self-report and observational data tend to concur, it is possible that experimental subjects attempt to present themselves in a particular light for various reasons, including fulfilling their perceptions of the experimenter?s expectations.

Both prospective and retrospective methods have been used to evaluate the psychological and behavioural effects of anabolic-androgenic steroids. However, any review of this topic must remain tentative due to the diversity of study designs and results. Conclusions drawn from earlier research and referred to in subsequent studies and reviews are frequently misleading because the results have been incorrectly interpreted originally or in secondary sources. Many of the reported behavioural effects have come primarily from studies using a small number of subjects, in which patients were administered anabolic-androgenic steroids for a variety of clinical conditions and these have found positive or unchanged moods and behaviour. Extremely small numbers of athletes have been studied, and the findings derived from patient populations can only be generalised to athletes with caution, particularly since athletes are known to use several drugs concurrently (Frankle et al. 1984), and to use black market drugs (Buckley et al. 1988; Burkett & Falduto 1984; CVM Update 1987; Frankle et al. 1984; Windsor & Dumitru 1989), the content of which may be suspect. Finally, the interaction effects of anabolic-androgenic steroids and environmental factors, stress levels, and often drugs of various types, including analgesics, anti-inflammatories, alcohol and other psychoactive substances, on feelings and behaviour remains unresolved in humans.

*10. Conclusions*
The few investigations conducted, primarily in prisoner populations, have shown a significant positive relationship between endogenous testosterone levels and aggressive behaviour. However, the questions of the extent of the relationship and of the interaction between testosterone and aggression remain unanswered. Do elevated testosterone levels result in more aggressive behaviour or does more aggressive behaviour cause testosterone levels to increase? In addition, what effect does the interaction of physical activity and an emotionally-charged environment (which not only reinforces but demands high levels of direct physical, and often, verbal aggression) have on testosterone production and behaviour? We do not even know the frequency or extent to which males become androgen-deprived as they age or the consequences for longevity or quality of life. Future research will undoubtedly need to examine the positive psychological effects of anabolic-androgenic steroid use as has occurred in the majority of patient samples. There may be significant numbers of individuals whose mental health has been improved through anabolic-androgenic steroid use.

Both medical and legal concerns regarding the psychological and behavioural effects of anabolic-androgenic steroids have been raised. Unfortunately, objective evidence documenting the short term psychological and behavioural changes accompanying and following anabolic-androgenic steroid use by athletes is extremely limited and is inconclusive. As indicated, many of the studies in this area suffer from methodological inadequacies such as small sample size, use of nonstandardised psychological inventories, and lack of appropriate control groups, among others. No acute adverse effects on mood or behaviour have been observed in individuals self-administering or clinically treated exclusively with non-17? -alkylated anabolic-androgenic steroids, suggesting that these effects may be unrelated to androgenic actions but rather the result of nonandrogenic properties arising from the 17? -alkylation and/or from binding to other than androgen receptors (Bardin et al. 1990; Friedl 1990; Janne 1990), or from interactions with other drugs. As Yesalis et al. (1989b,c, 1990a,b) and Cicero and O?Connor (1990) have pointed out, extremely little is known about the long term health impact of anabolic-androgenic steroids and their interactions with other drugs including drugs of abuse. Consequently, the need for much additional research is strongly indicated.

Although some athletes and coaches believe that anabolic-androgenic steroids exert a positive effect by enhancing performance through altered psychological states, others point out the potential negative effects of violent and aggressive behaviour. With present estimates of a million or more users in the US, an extremely small percentage of anabolic-androgenic steroid-using athletes appear to experience mental disturbances which result in their seeking clinical treatment, and of those who do, some may already suffer from existing mental health and/or substance abuse problems. At this point a cause-effect relationship has yet to be established. Moreover, of the seemingly small population of individuals who do experience significant psychological and behavioural changes, most apparently recover without legal or other problems when the use of androgens is terminated.


----------

