Written by Jose Antonio, Ph.D.
06 April 2007

The term “roid rage” gets thrown around like it’s conclusive scientific fact. Yet, the actual data on roid rage is actually quite the opposite. There is no evidence that anabolic steroid self-administration, per se, makes you any more aggressive than eating Twinkies or watching re-runs of Rambo movies. For instance, one study used a double-blind, placebo-controlled design that excluded competitive athletes and those with psychiatric disorders; the researchers gave subjects (43 eugonadal men, 19-40 years of age) a decent androgen dose (600 milligrams of testosterone enanthate (TE) per week). They were randomized to one of four groups, as follows. Group I: placebo, no exercise; Group II, TE, no exercise; Group III, placebo, exercise; Group IV, TE plus exercise. Exercise consisted of strength training sessions three times per week.

They used various measures, such as the Multi-Dimensional Anger Inventory (MAI), which includes five different dimensions of anger (inward anger, outward anger, anger arousal, hostile outlook and anger-eliciting situations) and a Mood Inventory (MI), which includes items related to mood and behavior. Subjects were administered these tests before, during, and after the 10-week intervention. Each subject's significant other (spouse, live-in partner, or parent) also answered the same questions about the subject's mood and behavior (Observer Mood Inventory, OMI). Guess what happened? Not a damn thing.  No temper tantrums. No throwing chairs.  And no throwing remote controls at the idiot box. Or in science language, they observed “no differences between exercising and nonexercising and between placebo- and TE-treated subjects for any of the five subdomains of MAI.” Thus, they concluded that “supraphysiological doses of testosterone, when administered to normal men in a controlled setting, do not increase angry behavior.”1 

So, with a dose of at least 600 milligrams per week of this particular androgen, no roid rage occurred. This, of course, doesn’t exclude the possibility that other androgens, longer treatment duration, or a different group of human subjects would result in the same response. Like any drug, there are individual responses and some drugs may elicit idiosyncratic effects.

Another factor is drug-drug interactions. For instance, scientists examined the effect of amphetamine on defensive reactivity and defensive aggression in Sprague-Dawley rats after chronic androgen treatment (daily intramuscular [i.m.] injections with 15 milligrams per kilogram bodyweight of nandrolone decanoate [ND] for 14 days). Defensive reactions in rodents occur in response to a real threat, but also to perceived provocation, such as that elicited by innocuous stimuli as reaction towards the experimenter. The defensive reactivity and aggression test employed in this study evaluates each rat's reaction toward four different stimuli: approach of a rod; startle to an air puff; poking with a rod at the flanks; and capturing with a gloved hand on two different occasions. 

As someone who has actually experimented with rats, I can say believe me, poking them with a rod or blowing air in their face is not the best way to make them your best friend. Far from it; doing that will turn them into Osama bin Rotten.   Nevertheless, immediately following the ND treatment period, no change in the defensive response was found. But an amphetamine challenge given three weeks after the last ND or vehicle injection induced a marked increased defensive aggressive response in the ND, compared to vehicle-pre-treated rats. The scientists concluded that “pre-treatment with ND modulates the behavioral response to amphetamine and induces long-lasting changes in the behavioral response.”2 So here you have nandrolone (a fairly mild androgen) having a “permissive” effect such that amphetamines promotes changes in behavior given the presence of nandrolone.  Would this happen with other androgens? Would this happen in humans? 

     New Designer Steroid
     A new androgen called Madol (17alpha-methyl-5alpha-androst-2-en-17beta-ol) has been recently identified. Madol was synthesized by Grignard methylation of 5alpha-androst-2-en-17-one and characterized by mass spectrometry and NMR spectroscopy. We developed a method for rapid screening of urine samples by gas chromatography/mass spectrometry (GC/MS) of trimethylsilylated madol (monitoring m/z 143, 270 and 345). A baboon administration study showed that madol and a metabolite are excreted in urine. Madol is only the third steroid never commercially marketed to be found in the context of performance-enhancing drugs in sports.3 I’d imagine Madol is just one of several designer drugs out there. I just find it odd that governments (at local, state, and federal level) spend countless dollars fighting a “steroid drug war” to prevent guys (and girls, I guess) from taking steroids to get bigger muscles (mainly for vanity reasons and for a small percentage of folks, performance enhancement), yet it’s okay to go under the knife and put yourself under the real risk of death by having fat sucked out of your gut, your face sliced with a machete to lift it, or to stick silicon balloons in your boobs.  (BTW, the latter procedure must be legal forever). 

IGF-1 – the Anti-Catabolic
What if you could produce a shitload of IGF-1 in your skeletal muscles?  Science fiction? Nope, science fact. Let me clarify. If you’re a rat, then have we got something for you. Localized over-expression of IGF-1 in tibialis anterior (TA) muscle was performed by injection of IGF-I cDNA followed by electroporation three days  before starting dexamethasone injections (0.1 milligrams per kilogram per day, subcutaneously).  In plainspeak, this is a way of genetically engineering your muscles such that you make lots of IGF-1.

Dexamethasone-induced atrophy of the tibialis anterior muscle as illustrated by reduction in muscle mass and fiber cross-sectional area. This muscle atrophy was paralleled by a decrease in the IGF-1 muscle content. As the result of IGF-I gene transfer, the IGF-1 muscle content increased twofold and muscle mass and fiber cross-sectional area increased in the TA muscle electroporated with IGF-1DNA.4  Bottom line: IGF-1 plays an important role in mitigating muscle atrophy. Imagine, though, if we could inject this stuff into healthy muscles, work out like crazy and take other effective “growth promoters?”

     Nandrolone: Effective and Safe
     In a randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of five percent or greater in the preceding year, or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 milligrams) or an equivalent volume of placebo every other week by intramuscular injection. Now for a guy, 100 milligrams per week ain’t much. But for women, that’s a pretty good dose. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. They found that nandrolone administration produced significant increases in weight and lean body mass during blinded treatment; however, fat mass did not change statistically significantly in either group. The researchers concluded that “nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases.”5      

Don’t you find it odd that the actual scientific data on androgen administration is the polar opposite of the verbiage you heard at the recent Congressional hearing related to steroids and baseball? Mmm… think about it. Someone is making stuff up. 

References
1.    Tricker R, Casaburi R, Storer TW, et al. The effects of supraphysiological doses of testosterone on angry behavior in healthy eugonadal men--a clinical research center study. J Clin Endocrinol Metab, Oct 1996;81(10):3754-3758.
2.    Steensland P, Hallberg M, Kindlundh A, Fahlke C, Nyberg F. Amphetamine-induced aggression is enhanced in rats pre-treated with the anabolic androgenic steroid nandrolone decanoate. Steroids, Mar 2005;70(3):199-204.
3.    Sekera MH, Ahrens BD, Chang YC, Starcevic B, Georgakopoulos C, Catlin DH. Another designer steroid: discovery, synthesis, and detection of 'madol' in urine. Rapid Commun Mass Spectrom, 2005;19(6):781-784.
4.    Schakman O, Gilson H, de Coninck V, et al. Insulin-like growth factor-I gene transfer by electroporation prevents skeletal muscle atrophy in glucocorticoid-treated rats. Endocrinology, Apr 2005;146(4):1789-1797.
5.    Mulligan K, Zackin R, Clark RA, et al. Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial. Arch Intern Med, Mar 14 2005;165(5):578-585.

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